Lipids & Menirals Metabolism

Biochem. 357
Third Year

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Lipids & Minerals

Contents
Lecture Title Page
No
Part I: Lipids
1 Definition, General characteristics& classification 2
2 Lipoproteins 15
3 Lipid Digestion 22
4 Oxidation of fats 23
5 Synthesis of fatty acids 34
6 Synthesis of triglycerides 39
7 Keton bodies metabolism 41
8 Lipoprotein metabolism 44
9 Cholesterol metabolism 54
12 Phospholidids metabolism 62
Part II: Minerals
1 Introduction & classification of minerals 70
2 Calcium & phosphorus 72
3 Magnesium & Sodium 77
4 Potassium & Chloride 80
5 Iron 81
6 Copper & Zinc 85
7 Iodine & Selenium 94
8 Manganese, Cobalt & Chromium 96
9 Molybedenum & Floride 97
12 Water metabolism 99
Practical Lipids and Minerals 122
References 139

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 Lipids & Minerals

Part I. Lipid Metabolism

Definition
 Biological molecules that are insoluble in aqueous solutions and soluble in
organic solvents, have some relation to fatty acids as esters, and have potentiality
of utilization by living organisms are classified as lipids.
 Lipids are composed of the elements C, H , & O. Lipids are a heterogeneous
group of compounds, including fats, oils, steroids, waxes, and related compounds,
which are related more by their physical than by their chemical properties. They
have the common property of being (1) relatively insoluble in water and (2) soluble
in nonpolar solvents such as ether and chloroform.
 They are important dietary constituents not only because of their high energy
value but also because of the fat-soluble vitamins and the essential fatty acids
contained in the fat of natural foods. Fat is stored in adipose tissue, where it also
serves as a thermal insulator in the subcutaneous tissues and around certain organs.
Nonpolar lipids act as electrical insulators, allowing rapid propagation of
depolarization waves along myelinated nerves. Combinations of lipid and protein
(lipoproteins) are important cellular constituents, occurring both in the cell
membrane and in the mitochondria, and serving also as the means of transporting
lipids in the blood. Knowledge of lipid biochemistry is necessary in understanding
many important biomedical areas, eg, obesity, diabetes mellitus, atherosclerosis,
and the role of various polyunsaturated fatty acids in nutrition and health.
General Characteristics:
1- All Lipids are hydrophobic. Consist of carbon, hydrogen and oxygen. Non-polar
(hydrophobic) compounds, soluble in organic solvents.
2- Contain fewer polar O-H bonds and more non-polar C-H bonds than
carbohydrates.

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3- Includes fats and oils, waxes, phospholipids, steroids, and some other related
compounds.
4- Large numbers of bonded hydrogen-therefore release a larger amount of energy
than other organic compounds.
5- Primarily energy sources and structural compounds and signaling molecules.
Function of lipids:
1) Energy storage source for animals.
2) Structural elements (plasma membrane) of cells and organelles.
3) Signal transduction molecules.
4) Sleep-inducing lipids recently identified.
5) Carrier of fat-soluble vitamin(VE,VA,VD)
6) Provide essential fatty acids (linoleic acid).
7) Provide glossy appearance, smooth taste.
8) Provide savory in the fry food.
Biomedical importance :-
1- Importance dietary constituent for their high energy value (main source of
energy).
2- Fat stored in adipose tissue serve as thermal insulator in the subcutaneous tissues
and around certain organs.
3- Non-Polar lipids act as electrical insulators allowing rapid propagation of
depolarization waves along myelenated nerves.
4- Lipoproteins (Combination of lipids and proteins) are important cellular
constituents occurring both in cell membrane and mitochondria, and serving for
lipid transportation into the blood.
5- Phospholipids and sterols make up about half the mass of biological membranes.
6- Lipids are important carriers for fat soluble vitamins.
7- Source of essential fatty acids.
8- Formation of some hormones.

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9- Some Lipids although are present in relatively small quantities , play crucial role
as enzyme co factor , electron carrier , light absorbing pigments and emulsifying
agents
10- Biological waxes find a variety of applications in the pharmaceutical, cosmetic
and other industries.
11- Knowledge of lipid biochemistry is necessary in understanding many
important biomedical areas, obesity, Diabetes mellitus, atherosclerosis and the role
of various polyunsaturated fatty acids in nutrition and health.
Classification of lipids:

(I) Simple lipids:

Simple lipids are esters of fatty acids with certain alcohols. They classified
according to the nature of alcohol into the following:
a) Fats and Oils:
 Fats: glycerol esters, solid at room temperature, fatty acids are saturated.
 Oil: glycerol esters, liquid at room temperature, fatty acids are unsaturated.
Fatty Acids: They are long chain linear hydrocarbons carboxylic acids. Usually
have an even number of C atoms (usually 12 to 20). The fatty acids are long, un-
branched monocarboxylic acids containing 10 to 22 carbon atoms. The carbons are

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numbered starting from the carboxylic C. They are amphiphilic; they have a polar
end and rest of the molecule is nonpolar.

The Fatty acids can be classified into families based on chain length and on the
number of C=C double bonds present. Saturated fatty acids contain no C=C double
bonds. (Saturated = bonded to the maximum number of hydrogen; Unsaturated
fatty acids contain C=C double bonds.
Melting Points: Increases with size (lesser effect), Decreases with unsaturation
(greater effect). Longer chain and saturation increases melting point of FA.

Cis vs Trans Fatty Acids

All naturally occurring double bonds have a cis-configuration 2 or more double
bonds exist as non-conjugated double bonds. Cis fatty acids occur naturally. Trans
fatty acids occur during hydrogenation reactions.

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The functions of fatty acids are:

o Biological fuel
o Components of more complex lipids
Clinical importance of fatty acids
• Fecal fatty acids are sometimes measured to detect mal-absorptive and
pancreatic disorders—the test is mostly considered obsolete
• Serum free fatty acids help distinguish between hyperinsulinemic hypoglycemia
(FFA normal) and disorders of fatty acid oxidation (FFA elevated and negative
ketones)
Chemical classification of Fatty acids
a) Saturated fatty acids: saturated fatty acids do not contain any double bonds or
other functional groups along the chain.
b) Unsaturated fatty acids: these contain double bonds.
Biological classification of Fatty acids:
a) Essential fatty acids
They are polyunsaturated fatty acids (linoleic, linolenic and arachidonic acids) that
cannot be synthesized by the body at sufficient rates and they must be supplied in
our diet.
b) Non-essential fatty acids
They are fatty acids than can be taken in diet or synthesized by the body.
Function of essential fatty acid
 Prevent fatty liver
 Membrane structure and function
 Proper development and functioning of the brain and nervous system
 Transport of cholesterol
 Formation of cell membrane
 Lipoprotein formation

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Fatty acid nomenclature:

Systematic name:
* Fatty acid are named after the hydrocarbon with the same no. of carbon atoms by
oic instead of e thus saturated f.A's end – anoic & unsaturated f.A's end-enoic
Saturated: parent hydrocarbon + oic (e.g. C18: Octadecanoic acid)
Unsaturated:
With one double bond: + enoic (e.g. C18: Octadecenoic acid)
With two double bonds: + dienoic (e.g.C18: Octadecadienoic acid)
With three double bonds: + trienoic (e.g. C18: Octadecatrienoic acid)

SATURATED FAs:
CN: M

Carbon Number of carbon atoms Number of double bonds:

C atoms are numbered from the carboxyl Carbon (C no.1) C adjacent to carboxyl C
(no 2 , 3 , 4) are also known as α , β , γ and the terminal methyl C is known as the ώ
or n-carbon. In IUPAC system the position of double bonds are indicated by symbol
Δn where n is the lower number carbon atom of each double bond pair.
Fatty acid reactions:
1) Salt formation: NaOH
RCO2H RCO2-Na+ (a soap)
Process of formation is known as saponification.

Ester formation:
2) Lipid peroxidation: -H20
RCO2R'
R'OH + RCO 2H
It is a non-enzymatic reaction catalyzed by oxygen. It may occur in tissues or in
foods (spoilage). The hydro-peroxide formed is very reactive and leads to the
formation of free radicals which oxidize protein and/or DNA (causes aging and
cancer).also, the principle is used in drying oils.

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R' O2
R R R'
H H non-enzymatic
OOH
very reactive
3) Hydrolysis:

4) Hydrogenation:

ω-3 Fatty Acids: The highest numbered C is called the ω-C. Sometimes FA is
classified according to the position of the first double bond from the ω-end. Most
polyunsaturated fatty acids are ω-6 fatty acids ω-3 fatty acids are found mainly in fish
and fish products. Also found in flax seeds ω-3 FAs inhibit formation of
thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation.
Thus, ω-3 FAs decrease the risk of heart disease.

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b) Waxes:
 Wax is а monoester formed from the reaction of а long-chain monohydroxy
alcohol with а fatty acid molecule.
 Paraffin wax is a mixture of solid hydrocarbons (normally straight-chain).
Waxes differ from fats in that fats contain chiefly esters of glycerol.
 Waxes are generally harder and less greasy than fats, but like fats they are less
dense than water and are soluble in alcohol and ether but not in water.
 Biological role: They serve as protective coatings on leaves, stems, and fruit of
plants and the skin and fur of animals.

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 Due to their high molecular weights, waxes are generally solids at room
temperature. Waxes are found naturally as coating on fruits, leaves, insect
exoskeleton (water retaining). Birds have glands producing wax for feathers (water
repelling).
Neutral lipids:
–Glycerides:
• Triglycerides from plants tend to have large amount of C18:2 or linoleic
residues and are liquid at room temperature (RT). Triglycerides from animals
especially ruminants, tend to have C12:0 through C18:0 fatty-acid residues
(saturated fats) and are solid at RT.

Glycerol backbone with FA attached by ester bonds. Each FA can be different.

Triglycerides with saturated FA (no kinks). Pack tightly → solid at room tempt.
Triglycerides with unsaturated FA typically oils at room temp.
Source of Triglycerides:
–Exogenous source: Dietary
–Endogenous: Liver and tissue storage
• Triglycerides transported by Chylomicrons (exogenous) and VLDL (endogenous)
• Energy source when plasma glucose is decreased
–Triglycerides catabolism is regulated by: lipase, Epinephrine, and cortisol
• Triglycerides are formed by combining glycerol with three molecules of fatty
acid. Alcohols have a hydroxyl (HO-) group. Organic acids have a carboxyl
(COOH) group. Alcohols and organic acids join to form esters. The glycerol
molecule has three hydroxyl (HO-) groups.

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• Each fatty acid has a carboxyl group (-COOH). In triglycerides, the hydroxyl
groups of the glycerol join the carboxyl groups of the fatty acid to
form ester bonds.

Chemical properties
 Hydrolysis: There is acetic, basic and enzyme’s hydrolysis (Acidic and

enzyme). Triglycerides are broken down in small intestine by the action of lipase
enzyme which is synthesized in the pancreas and is secreated into small intestine.
Pancreatic lipase catalyzes the hydrolysis of the primary esters at C1 and C3 of
triglyceride to generate monoacylglycerol and fatty acids.

Action of phospholipase enzyme:

On the basis of the ester bond that is cleaved within a phospholipid molecule,
phospholipases are grouped into four families, namely A, B, C and D.
Phospholipase A enzymes cleave the acyl ester bond at either the sn-1
(phospholipase A1) or sn-2 (phospholipase A2) position.

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The Whoterm phospholipase B is given to phospholipases that hydrolyze acyl ester

bonds at both sn-1 and sn-2 positions. Enzymes grouped under phospholipase C
cleave the glycerophosphate bond, while phospholipase D enzymes remove the
polar head group.

(II) Compound Lipids:

Complex lipids are bonded to other types of molecules. This group includes the
following important members:
Phospholipids: Most phospholipids contain a diglyceride, a phosphate group, and a
simple organic molecule. A phospholipid molecule consists of a hydrophilic polar
head group and a hydrophobic tail. The polar head group contains one or more
phosphate groups. The hydrophobic tail is made up of two fatty acyl chains. They are
a major component of all cell membranes as they can form lipid bilayers.

 Phospholipids are the principal components of the myelin sheaths of neurons.

Examples of phospholipids include lecithin, cephalins, phosphoinositides (in the
brain), and cardiolipin (in the heart).

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Bio-membranes:
Make up boundaries of cells and intracellular organelles (nucleus, Golgi,
mitochondria, ER, etc.). Membranes are dynamic fluid structures. It is composed of a
lipid bilayer with proteins. It is embedded within the bilayer. Lipids responsible for
semi-permeability of bio-membranes; hydrophobic chemicals can penetrate, but most
polar molecules are excluded. Membrane proteins are transporters, channels and
pumps for the selective entry of specific molecules.
Lipid Bilayers:
Phospholipids are amphipathic: They have both
hydrophilic and hydrophobic regions. The two
hydrocarbon chains are parallel to each other; the polar
group is extended in the opposite direction.
In aqueous solutions, amphipathic molecules arrange themselves as micelles,
bilayers or liposomes. These structures are stabilized by hydrophobic interactions
between hydrocarbon chains and hydrogen bonds between polar head groups and
H2O. Phospholipids and glycolipids favor the lipid bilayer over micelles because the
interior of a micelle cannot accommodate 2 hydrocarbon chains of each molecule.
Salts of fatty acids (soaps) prefer to organize as micelles.
Glycolipids: are lipids with a carbohydrate attached. Their role is to provide energy
and also serve as markers for cellular recognition. Glycolipids include the
cerebrosides, the sulfatides, and the gangliosides. The cerebrosides are characterized
by a single monosaccharide head group. Sulfatides are a sulfate group containing
derivative of the cerebroside galactocerebroside. Gangliosides are glycolipids
possessing oligosaccharide groups, including one or more molecules of N-
acetylneuroaminic acid (sialic acid).
Sulfolipids: are classes of lipids which possess a sulfur-containing functional group.
One of the most common consituents of sulfolipids is sulfoquinovose, which is

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acylated to form sulfoquinovosyl diacylglycerols. In plants, sulfolipids are important

intermediates in the sulfur cycle.
Lipoproteins: lipoprotein is a biochemical assembly that contains both proteins and
lipids whose function is to transport water-insoluble lipids in the water-based
bloodstream. The lipids or their derivatives may be covalently or non-covalently
bound to the proteins.
The function of lipoprotein particles is to transport lipids (fats) and cholesterol
around the body in the blood.
There are 4 major classes of plasma lipoproteins: VLDL ―Very Low Density
Lipoprotein‖, LDL ―very Low Density Lipoprotein‖, HDL ―High Density
Lipoprotein‖
(III) Derived Lipids: lipids are obtained on hydrolysis of simple and complex lipids.
These lipids contain glycerol and other alcohols. This class of lipids includes steroid
hormones, ketone bodies, hydrocarbons, fatty acids, fatty alcohols, mono and
diglycerides, terpenes and carotenoids. These are sometimes present as waste
products of metabolism.
Cholesterol:
• Unsaturated steroid alcohol - amphipathic
• 4 ring structures (A, B, C, D) with single side R
chain (like FA)
• Hydrophilic OH on A ring
• 4 rings and side chain internal, OH external
Miscellaneous lipids
These include compounds, which contain characteristics of lipids. They include
squalene, terpenes, hydrocarbons, carotenoids, etc.

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Quiz 1

1. Lipids are the body's major reserve of energy.

(a) True (b) False
2. Lipids are insoluble in water (hydrophobic).
(a) True (b) False
3. All of the following is complex lipids, except
a. Phosphatidic acid b. Cerebroside c. Cardiolipin d. Cholesterol
4. Which of the following is essential fatty acid?
a. Linolenic acid b. Arachidonic acid
c. Oleic acid d. Palmitic acid
5. An example of a saturated fatty acid is
(A) Palmitic acid (B) Oleic acid
(C) Linoleic acid (D) Erucic acid
6. Phospholipid acting as surfactant is
(A) Cephalin (B) Phosphatidyl inositol
(C) Lecithin (D) Phosphatidyl serine
7. Which of the following is/are unsaturated fatty acids?
a) Linoleic acid b) Oleic acid
c) Palmitoleic acid d) All of these
8. Liquid form of triglycerides at ordinary room temperature are called
a) Oils b)Solid c) Fats d) None of these

9. Hydrolysis of fats by alkalies into fatty acids and glycerol is called

a) Coagulation b) Saponification
c) Suspension d) Colloidal

10. Examples of monounsaturated fatty acids are:

a) Oleic acid b) Arachidonic acid
c) Palmitic acid d) Linolenic acid

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Lipoproteins
 Lipoproteins are spherical particles with non-polar lipids (triglycerides and
cholesterol esters) in their core and more polar lipids (phospholipids and free
cholesterol) oriented near the surface.
 They also contain one or more specific proteins called Apo-lipoproteins that are
located on their surface.
 Lipids need to be transported to tissues and organs to perform their metabolic
functions.
 Triglycerides & cholesterol esters are hydrophobic. There should be a form of
hydrophilic compound.
 Lipids are transported by a series of micelles called lipoproteins.
 General structure – spherical, 10 - 1200 nm.
 Lipoproteins composed of lipids & proteins (apolipoprotein).
 Cholesterol and phospholipids on surface monolayer.
 Triglycerides and cholesterol esters in center.
 Size correlates to lipid content. Larger particles have more lipid core. Relatively
more triglycerides & cholesterol esters.
 Larger lipid to protein ratio. Lighter in density
 Various lipoproteins were separated by ultracentrifugation into different
density fractions:
1. Chylomicrons,
2. Very Low Density Lipoproteins (VLDL),
3. Low Density Lipoproteins (LDL),
4. High Density Lipoproteins (HDL)
Apo-lipoproteins:
 Primarily on surface of lipoprotein particle. Maintain structural integrity,
recognition of cell surface receptors. Activators & inhibitors of various enzymes that

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modify lipoprotein particles. Amphipathic helix. Hydrophobic a.a residues interact

with lipids. Hydrophilic a.a resides interact with aqueous environment.
Apo A-1: major protein of HDL. Apo B: Primary protein of LDL, VLDL and
chylomicrons. Apo C: Chylomicrons, VLDL, and HDL. Apo E: LDL, VLDL, HDL.

Plasma lipoprotein another name % of % of Main Main

By ultracentrifugation by electrophoresis lipids protei lipid Apoprotein
n

1- Chylomicrons Non-mobile 99 1 TAG Apo- B-48

2-Very low density Pre- 90 10 TAG Apo- B-100

lipoprotein (VLDL) betalipoproteins

3-Low density Beta 80 20 CE & PL Apo- B-100

lipoprotein (LDL) (b-lipoproteins)

4-High density Alpha 60 40 PL, C & CE Apo- A

lipoprotein (HDL) (a- lipoproteins)

FFA-Albumin Not a real lipoprotein 1 99 FFA Albumin

Functions of apo-lipoproteins:
1. They serve to solubilize plasma lipids.
2. Activate enzymes involved in lipid metabolism (LCAT, LPL).
3. Maintain structural integrity of lipid/protein complex.
4. Delivery of lipids to cells via recognition of cell surface receptors.

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Plasma lipoproteins can be separated and fractionated by two methods:

Ultracentrifugation and Electrophoresis:
Separation of plasma lipoproteins
-
Non-mobile
Chylomicron
Prebeta lipoprotein
VLDL Pre-b

Beta lipoprotein
LDL
b

Alpha lipoprotein
HDL
a
FFA-Albumin
FFA-Albumin
+
Ultacentrifugation Electrophoresis

1) Chylomicrons:
 It was in the epithelial cells of the small intestines
(enterocytes). Contain apo B-48 lipoprotein.
 Apoproptein: (also called apolipoprotein) the protein
ingredient of lipoproteins. Integral protein: it is an essential
component protein which is penetrating through the whole thickness of the
phospholipid layer of lipoprotein particle.
 Peripheral protein: surface protein component of the lipoprotein which can be
exchanged between different types of lipoproteins and act as enzyme activator or
receptor binding site. Centrifugal transport: transport of lipids from liver to the
peripheral tissues, e.g. adipose tissue and muscles. Centripetal transport: transport of
lipids from peripheral tissues to the liver.
 Structure: mature chylimicrons are about 1µ in diameter and consist of 2%
proteins (apoB48, apoA. apoC and apoE) and 98% lipids (mainly triglycerides).
 Function: transport of the absorbed dietary (exogenous) triglycerides to the
tissues. They also transport dietary cholesterol and fat soluble vitamins to the liver.

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2) Very low density lipoproteins (VLDL):

 Synthesis: in the liver cells (hepatocytes). The triglyceride component is
synthesized de novo or by re-esterification of free fatty acids.
 The apo-lipoprotein (apoB100) is synthesized in the microsomes. The VLDL in
this form is called nascent and is secreted into the sinusoids. They venous circulation
where they receive apoC and apoE from HDL to become mature VLDL.
 Structure: VLDL consists of 10% proteins (apoB100, apoC and apoE) and 90%
lipids (mainly triglycerides).
 Function: centrifugal transport or the endogenous triglycerides.

3)Low density lipoproteins (LDL):

 Synthesis: LDL is formed of IDL (VLDL remnants) after exchange of
triglycerides for cholesterol ester with HDL and loss of apoE.
 Structure: LDL consists of 20% proteins (apoB100) and 80% lipids (mainly
cholesterol).
 Fate: the LDL binds to specific LDL receptors in the liver and peripheral tissues,
and then it is up taken and hydrolyzed to give cholesterol.
 Function: important source of cholesterol for peripheral tissues.
4) High density lipoproteins (HDL):
 Synthesis: HDL is synthesized in the cells of liver and small intestine as discoidal

HDL.
 Structure: HDL consists of 32-55% proteins (apoA, apoC, apoE and apoD) and

45-68% lipids (phospholipids and cholesterol).

 Fate: the HDL receives free cholesterol from tissues. This cholesterol may get

esterified with fatty acids by means of LCAT (licethine cholesterol acyl transferase).
The cholesterol esters are stored between the phospholipid bilayer transforming
discoidal HDL to spheroidal HDL. Later on cholesterol esters may be given to
chylimicron remnants or VLDL remnants in exchange for triglycerides by means of
apoD (CETP cholesterol ester transfer protein).

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 Function: centripetal transport of cholesterol (reverse cholesterol transport

pathway). Reservoir for apoE and apoC needed for maturation of chylimicrons and
VLDL.

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Quiz 2
1. High content of Triglycerides are seen in
a) LDL b) HDL c) VLDL d) Chylomicrons
2. Dietary fats after absorption appear in the circulation as
(A) HDL (B) VLDL (C) LDL (D) Chylomicron
3. Free fatty acids are transported in the blood
(A) Combined with albumin (B) Combined with fatty acid binding protein
(C) Combined with β -lipoprotein (D) In unbound free salts

4. HDLs are synthesized in

A. blood B. liver

C. intestine D. pancreas

5. What is the major protein constituent of high-density lipoprotein (HDL)?

A. Apolipoprotein A-l

B. Apolipoprotein C-l

C. Apolipoprotein E

D. None of these

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Lipid Metabolism
Digestion:
(1) Mouth: No digestion
(2) Stomach: Although there is gastric lipase yet it is of no significance in adult. It is
active only in children, due to optimum pH.
(3) Pancreas: Pancreatic lipase enzyme hydrolyses the triglycerides glycerol and 3
fatty acids.

CH2OOCR1 Lipase CH2OH

CHOOCR2 CHOH + 3 RCOOH
CH2OOCR3 3H2O CH2OH Fatty acid
Triglyceride "Lipolysis" glycerol

 The process for digestion needs bile salts, which have the property of lowering the
surface tension (hydrotropic action or Emulsifying action).
Absorption:
- Glycerol of and short chain fatty acids are water soluble. They are absorbed by
diffusion to portal circulation.
- Long chain fatty acids pass to intestinal cells together with un-hyohrlysed mono
and diglycerides, and, they are re-synthesized again into Triglycerides.
- These form chylomicrons, which are absorbed to lymphatic to general circulation.
Lipid Pathways:
 Average person takes in 60-130 grams of fat per day. Mostly triglycerides.
Pancreatic lipase cleaves FA. Triglycerides → mono or diglycerides. Cholesteryl
esters → free cholesterol. These amphipathic molecules aggregate in intestine with
bile acids into micelles.
 Micelles contact intestinal villi and are absorbed – passive and active transport.
Smaller FA (<10 carbons) absorbed directly into portal circulation. Larger fragments

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converted back into triglycerides & cholesteryl ester. Packaged chylomicrons with
apo B-48. > 90% absorption effectiveness for triglycerides but only 50% for
cholesterol.

 FAs, glycerol, and monoglycerides are absorbed by cells of the small intestine and
reassembled into triglycerides in the intestinal cells. Triglycerides are broken down
into FAs and glycerol by lipoprotein lipase which is found attached to the walls of the
blood vessels. Short and medium chain fatty acids enter directly into the blood
stream. Long chain fatty acids are packaged into chylomicrons which can enter the
lymphatic system and eventually the bloodstream.
 FAs are then absorbed into body cells and tissues and the glycerol recirculates back
to the liver. Muscle cells can use FAs immediately for fuel. Fat (adipose) cells
repackage FAs into triglycerides. Chylomicron remnants go back to the liver and are
recycled.
 The liver takes up lipids from the blood and also manufactures other lipids and
cholesterol. Uses FAs from bloodstream. Carbon and hydrogen from carbohydrates,
protein, and alcohol. Repackages these new lipids as lipoproteins for transport to the
body Called: VLDL, LDL, and HDL.

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Fate of absorbed lipid:

-1- Uptake by tissues: %92of TAG in chylomicrons are hydrolyzed by lipoprotein
lipase enzyme (LPL) in extra-hepatic tissues mainly adipose tissue and muscles. The
fatty acids are uptake by these tissues and again stored as TAG. LPL hydrolyzes
TAG of chylomicrons leaving chylomicron remnants. The liver takes up the
chylomicron remnants by endocytosis.
2- Utilization by tissues: TAG in chylomicrons is degraded to free fatty acids (FFA)
and glycerol by LPL.
3- Storage: Triacylglycerol's are stored mainly in adipose tissue as depot fat.
4- Secretion: Triacylglycerol's are secreted in milk (from lactating mammary glands)
and in sebum (from sebaceous glands).
 Fate of free fatty acids (FFA): Most cells uptake FFA and either store them as
TAG or can oxidize FA to produce energy.
 Fate of glycerol: In the liver, glycerol forms glycerol 3-phosphate, then
dihydroxyacetone phosphate (DHAP) which can be oxidized by glycolysis or form
glucose by gluconeogenesis.

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Oxidation of fats
Triglycerides are hydrolyzed by lipase enzyme glycerol of and fatty acids. So, fat
oxidation includes:
(1) Oxidation of F.A.
(2) Oxidation of glycerol
(I) Oxidation of fatty acids
CH3 …….. CH2 - CH2 - CH2 - COOH
Fatty acids are oxidized by 3 theories:
(1) β-Oxidation
(2) α- Oxidation
(3) ω - Oxidation
(1) β - Oxidation of fatty acids: " Knoop's theory 1905 "
 β - Oxidation of fatty acids occurs in the Mitochondria.
 Enzymes responsible for β-Oxidation are collectively called "fatty acid Oxidases"
and they are located in the mitochondrial matrix.
Steps :
(1) Fatty acids are activated in the outer mitochondrial membrane.

Thiokinase
R-CH2 - CH2 - COOH R-CO ~ SCOA
Acyl COA
ATP AMP
2 high energy bonds are consumed.
(2) Acyl COA cannot traverse the inner mitochondrial membrane, so, Carnitine is
used as carrier:
(a) Acyl COA reacts with carnitine in the outer membrane to Acyl carnitine. Enzyme
responsible Carnitinc Acyl transferase I.
(b) Acyl carnitine is transported across the inner membrane by carrier protein.

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(C) Carnitine is liberated and acyl COA is re-formed by Carnitine Acyl Transferase
II.

(3) Acyl COA is dehydrogenated by Acyl COA dehydrogenase. FAD carries H2 to

α, β-unsaturated acyl COA.
This reaction is irreversible.
(4) α, β-.unsaturated acyl COA is hydrated to β-hydroxy acyl COA.
(5) β-hydroxy acyl COA is dehydrogenated by β-hydroxy acyl COA dehydrogenease.
NAD carries H2 to β-keto Acyl COA.
(6) B- keto Acyl CoA is splitted by thiolase enzyme to Acyl COA which is less than
original by 2 carbons, and Acetyl COA which join kreb's cycle.
(7) Process is repeated till the F.A. is completely broken to Acetyl CoA.
Energy gain : [ (N/2-1) × 5 ATP ] + [ (N/2 × 12 ATP)] -2 ATP
N = number of carbon atoms.
e.g.- Take palmitic acid C16 as an example.
- This acid in β-oxidation to 8 acetyl COA and it undergoes 7 revolutions in β-
oxidation cycle.
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 Lipids & Minerals

- Each cycle produces NADH2 & FADH2 which join the respiratory chain
NADH2 3 ATP.
FADH2 2 ATP.
- Acetyl COA in kreb's cycle 12 ATP
.. So total gain
8 × 12 + 7(3+2) = 96 + 35 = 131 ATP.
2 ATP were consumed in FA oxidation.
.. Net = 131 – 2 = 129 ATP.

Steps of Beta-oxidation
Activation of fatty acids:
 Fatty acids must be first converted to an active intermediate before they are
catabolized. This is the complete degradation of fatty acids that require energy
from ATP. In the Presence of ATP and COA, the enzyme acyl-COA
synthetase catalyze the conversion of fatty acid to acyl COA (active fatty acid)
using one ATP and forming AMP + PPi
 PPi use another ATP in presence of phosphatase enzyme to complete the
reaction.

Penetration of long chain fatty acids through mitochondria membrane:

 Beta oxidation of fatty acids takes place in the mitochondrial matrix for the
most part. However, fatty acids have to be activated for degradation
by coenzyme A by forming a fatty acyl-CoA thioester. For short and medium
length fatty acids, they undergo this reaction in the mitochondria. The long
chain fatty acids can't go through the membrane though, so this reaction occurs
at the outer mitochondrial membrane and the product has to be carried by
carnitine across the inner mitochondrial membrane. They are made into

27
Lipids & Minerals

acylcarnitine derivatives by carnitine transferase I on the outer side of the inner

membrane.
 These are then transported across the membrane by a translocase and then they
are passed to carnitine acyltransferase II on the matrix side which puts the fatty
acyl group back on CoA leaving the original fatty acyl-CoA.
Along with this "activation" step, Beta oxidation of saturated fatty acids
consists of a recurring cycle of a series of four steps.

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Lipids & Minerals

R – CH2 – CH2 – COOH

COASH ATP
Thiolase AMP + PPi
H2O
In the mitochondrial matrix R – CH2 – CH2 CO ~ SCOA

Acyl COA R – CH2 – CH2 CO ~ SCOA

FAD
Acyl COA dehydrogenase
FADH2

α , β -unsaturated R – CH = CH CO ~ SCOA
Acyl COA
Hydratase H2 O

β-hydroxy Acyl COA R – CH – CH2 CO ~ SCOA

OH
β-hydroxy Acyl NAD
COA dehydrogenase
NADH2

O
β -keto Acyl COA R – C – CH2 CO ~ SCOA

Thiolase COA – SH

R – CO ~ SCOA
β-oxidation theory +
Knoop 1905 CH3 CO ~ SCOA

To kreb's cycle

12 ATP

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 Lipids & Minerals

Oxidation
This first reaction is the oxidation of the Ca-Cb bond. It is
catalyzed by acyl-CoA dehydrogenases. This catalyst is a
family of three soluble matrix enzymes. These enzymes carry
non-covalently bound FAD that is reduced during the oxidation
of the fatty acid. This is an oxidation reaction and it should be
similar to that of the succinate dehydrogenase reaction of the
TCA cycle because the first three steps of this pathway are
directly analogous to the steps needed to get succinate to
oxaloacetate.
1- Hydration
The second reaction in this pathway is one in which water is
added across the new double bond to make hydroacyl-CoA. The
catalyst in this reaction is Enoyl-CoA hydratase. This is also called a crotonase and it
converts trans-enoyl-CoA to L-B-Hydroxyacyl-CoA. This reaction would be
classified as a hydration reaction because you are adding water.
2- Oxidation
The third reaction of this pathway is the oxidation of the
hydroxyl group at the beta position which forms a beta-
ketoacyl-CoA derivative. This is the second oxidation step in
this pathway and it is catalyzed by L-Hydroxyacyl-CoA
Dehydrogenase. This enzyme needs to have NAD+ as a
coenzyme and the NADH produced represents metabolic
energy because for every NADH produced, it drives the
synthesis of 2.5 molecules of ATP in the electron transport
pathway. So, this reaction is classified as an oxidation
reaction.

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 Lipids & Minerals

4- Cleavage
The fourth and final reaction of this pathway is the thiolase catalyzed reaction. This
reaction cleaves the beta-ketoacyl-CoA. The products of this reaction are an acetyl-
CoA and a fatty acid that has been shortened by two carbons. So, this reaction is
classified as a cleavage reaction.
Example: β-oxidation of myristic acid (14C)

Example: Palmitic Acid is C-16

• Initiating Step - requires 2 ATP
• Step 1 - FAD = 2 ATP
• Step 3 - NAD= 3 ATP

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 Lipids & Minerals

• Total ATP per turn of spiral = 5 ATP

• Example with Palmitic Acid = 16 carbons = 8 acetyl groups
• Number of turns of fatty acid spiral = 8-1 = 7 turns
• ATP from fatty acid spiral = 7 turns and 5 per turn = 35 ATP.
NET ATP from Fatty Acid Spiral = 35 - 2 = 33 ATP
7NADH x 3 ATP 21
7 FADH2 x 2 ATP 14
8 Acetyl CoA x 12 ATP via Krebs CAC 96
Total 131 ATP
Less 2 ATP
NET 129 ATP
From one molecule of palmitoylCoA
Importance of β-oxidation:
• Source of energy: as oxidation of fatty acids is a major source of energy to the
body during starvation.
• Production of acetyl COA: which is converted to several useful compounds such
as cholesterol, acetylcholine, ect….).
• Formation of keton bodies that serve as fuel for extra hepatic tissue.

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 Lipids & Minerals

(2) Alpha oxidation ( α-oxidation )

– It occurs in brain tissue, specialized for oxidation of F.A which have methyl group
CH3 at the β-position. In these acids, the β- oxidation is blocked. So,
(1) F.A is hydroxylated at the α- position into α-hydroxyl acid.
Now, the methyl group is at α-position. And B-oxidation occurs.

 It is a minor pathway for oxidation of phytanic acid (= branched-chain FA with

methyl group in the β-carbon).
 Phytanic acid is derived from animal fat and cow’s milk. It cannot undergo b-
oxidation.
 It occurs mainly in the brain and liver.
 Deficiency of the enzymes of α-oxidation leads to accumulation of phytanic acid in
the brain, a disease known as Refsum disease (phytanic acid storage disease) which is
characterized by mental retardation, deafness, & blindness at young age.
 Refsum disease is a genetic disease common in Jewish.
(3) Omega oxidation (ω-oxidation)
 Enzymes are present in liver microsomes.
 The ω carbon is oxidized into COOH. To produce dicarboxylic acid

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 Lipids & Minerals

CH3 COOH
(O)
HOOC …. (CH2)n …… COOH
 β-oxidation can occur on both sides, and
finally molecules of acetyl COA
+
Succinyl coA

Succinic acid

Oxidation of fatty acids with odd number of carbon atoms :

 The majority of natural lipids contain an even number of carbon atoms. A small
proportion of plant derived lipids contain odd numbers and upon complete β-
oxidation these yield acetyl-CoA units plus a single mole of propionyl-CoA.
 The propionyl-CoA is converted, in an ATP-dependent pathway, to succinyl-CoA.
The succinyl-CoA can then enter the TCA cycle for further oxidation .

 Oxidation of unsaturated fatty acids :

 It is the same as saturated fatty acids through β-carbon atom.

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 Lipids & Minerals

 The oxidation of unsaturated fatty acids presents some difficulties, yet many such
fatty acids are available in the diet .
 Most of the reactions are the same as those for saturated fatty acids. In fact, only
two additional enzymes—an isomerase and a reductase— are needed to degrade a
wide range of unsaturated fatty acids.

R – CH2 – CH2 – CH = CH CO ~ SCOA

H2O α, β , acyl COA
Enoyl hydratase
R – CH2 – CH2 – CH – CH2 – CO ~ SCOA
OH NAD β -hydroxy acyl COA
Dehydrogenase
NADH2
R – CH2 – CH2 – CO – CH2 – CO ~ SCOA
β-keto acyl COA
COASH
β - keto thiolase

R – CH2 – CH2 – CO ~ SCOA CH3 – CO ~ SCOA

Acyl COA – 2 carbon atom Acetyl COA

Creb's cycle

 The β-oxidation pathway accomplishes the complete degradation (Lipolysis) of

saturated fatty acids having an even number of carbon atoms. Most fatty acids have
such structures because of their mode of synthesis.
 The oxidation of fatty acids containing double bonds requires additional steps.
 Likewise, fatty acids containing an odd number of carbon atoms yield a propionyl
CoA at the final thiolysis step that must be converted into an easily usable form by
additional enzyme reactions.

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 Lipids & Minerals

Regulation of Lipolysis in Adipose Tissue

 CHO feeding increases insulin which represses the synthesis of HSL and inhibits
it, so CHO feeding and insulin inhibits lipolysis.
 Fasting decreases insulin and increases anti-insulin hormones which induce the
synthesis of HSL and stimulate it, so fasting and anti-insulin hormones stimulate
lipolysis.
 Anti-insulin hormones include: Adrenaline, glucagon, glucocorticoids, thyroxine,
and growth hormone.
 In diabetes mellitus (DM), lipolysis is markedly increased because of insulin
deficiency.
 This causes hyperlipemia in DM especially type 1 (IDDM). Caffeine (in coffee,
tea and cola) stimulates lipolysis.

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 Lipids & Minerals

Quiz 3
1. What would be the consequences of inhibiting the carnitine shuttle which transports fatty
acids into the mitochondria?
a) Increase in blood glucose concentration.
b) Accumulation of fat droplets in liver and muscle.
c) Increase in fatty acid synthesis in the liver.
d) Low levels of long chain free fatty acids in the blood.

2. Which of the following statements about the oxidation of fatty acids is correct?
a) Fatty acid oxidation in peroxisomes does not generate ATP.
b) Fatty acids are oxidised on the outer mitochondrial membrane.
c) Most fatty acids are oxidised in peroxisomes.
d) Fatty acid oxidation forms FADH2 in the cytoplasm.
3. The enzymes of β-oxidation are found in
(A) Mitochondria (B) Cytosol (C) Golgi apparatus (D) Nucleus
4. β-Oxidation of fatty acids requires all the following coenzymes except
(A) CoA (B) FAD (C) NAD (D) NADP

5. Which of the following can be oxidized by β-oxidation pathway?

(A) Saturated fatty acids (B) Monosaturated fatty acids
(C) Polyunsaturated fatty acids (D) All of these

6. Propionyl CoA is formed on oxidation of

(A) Monounsaturated fatty acids (B) Polyunsaturated fatty acids
(C) Fatty acids with odd number of carbon atoms (D) None of these

7. Carnitine acylcarnitine translocase is present

(A) In the inner mitochondrial membrane (B) In the mitochondrial matrix
(C) On the outer surface of inner mitochondrial membrane
(D) On the inner surface of inner mitochondrial membrane

8. Net ATP generation on complete oxidation of stearic acid is

(A) 129 (B) 131 (C) 146 (D) 148

9. Propionyl CoA formed oxidation of fatty acids having an odd number of carbon atoms is
converted into
(A) Acetyl CoA (B) Acetoacetyl CoA
(C) D-Methylmalonyl CoA (D) Butyryl CoA
10. α-Oxidation of fatty acids occurs mainly in
(A) Liver (B) Brain (C) Muscles (D) Adipose tissue

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 Lipids & Minerals

Biosynthesis of fatty acids (Lipogenesis)

Lipogenesis is the process of synthesis of triglycerides mainly from glucose. It occurs
in the liver adipose tissue and lactating mammary glands.
The process involves:
i. Synthesis of fatty acids.
ii.Synthesis of Glycerol.
iii. Synthesis of Triglycerides.
Biosynthesis of fatty acids: This process passes through 3 systems:
-Extra mitochondria system (cytoplasmic) main
-Mitochondrial system.
-Microsomal system.
Biosynthesis of glycerol:
It is synthesized from glucose through glycolysis to dihydroxy acetone phosphate
which is reduced to α-glycero-phosphate.

(I) Synthesis of fatty acids

- Fatty acids are synthesized by 3 systems.
(1) Extra mitochondrial (cytoplasmic) system.
(2) Mitochondrial system.
(3) Microsomal system.
(1) Extra mitochondrial "cytoplasmic"
" Do Novo synthesis of F.A "
- It occurs in the cytoplasm.
- It concerned with De Novo synthesis of fatty acids from Acetyl COA.
- Enzymes:
Those of fatty acid synthesis are multi enzyme complex. This is composed of 2
polypeptide chains (Dimer).

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 Lipids & Minerals

Each chain is composed of ACP "Acyl carrier protein" and 7 enzymes. Enzymes
cannot be separated from each other's without loss of activity.
- ACP of each monomer contains 4-phosphopante-theine, which possess SH group.
- These SH groups become esterified with carboxylic group of acid during synthesis.
- Only the dimer is active, it's SH groups alternate in their function first carrying acyl
group, then malonyl group.
- The majority of the fatty acids required supplied through our diet. Fatty acids are
synthesized whenever there is a caloric excess in the diet.
- The excess carbohydrate and protein obtained through diet can be converted to
fatty acids which are stored as triacylglycerol. Fatty acid synthesis involves the
similar steps involved in b-oxidation of fatty acid but in a reverse way.
Steps :
(1) CO2 is fixed to Acetyl COA to Malonyl COA. This is catalyzed by " Acyl COA
Carboxylase " which is the key enzyme of fatty acid synthesis .

(2) Acetyl COA condenses with SH group of ENZYME to Acetyl enzyme.

(3) Malonyl COA Condenses with the other SH group to Acetyl malonyl enzyme.
(4) Acetyl redical is transferred from ENZ.1 to condense with malonyl radical, CO2
is liberated to β-keto Acyl Enzyme.
(5) From now on wards the steps are similar to β-oxidation in the reverse direction.
(6) Reductase & NADPH2 to β -hydroxy Acyl ENZ.
(7) Dehydratase to α, β - unsaturated Acyl ENZ.
(8) Reductase & NADPH2 to ACYL ENZ. "Butyryl ENZ."

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 Lipids & Minerals

(9) The Acyl radical can be transferred to the 1st subunit of the enzyme. ENZ.1
allowing the 2nd subunit to condense with new malonyl COA, thus adding 2 carbons
each cycle.
(10) After 7 cycles palmitic acid is formed and separated from the enzyme. By
Deacylase.

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 Lipids & Minerals

Fate of plamitate:
The free palmitate must be activated to palmityl-COA before it can proceed via any
other pathway.
1- Estrification:
Palmitate may undergo estrification with glycerol or cholesterol.
Palmitate + glycerol acyl-glycerol.
Palmitate + cholesterol cholesterol esters.
2- Chain elongation:
Palmitate may be elongated to form a fatty acid having a no. of carbon atoms more
than 16.
3- Desaturation:
(formation of unsaturated fatty acids) where it can be elongated to form stearic acid
then undergo desaturation at C9 and C10 to form oleic acid (unsaturated fatty acid).
4- Sphingosin formation:
Where palmitoyl COA combines with amino acid serine.

The growing
chain of fatty
acid is
continually bound to the ENZ. and is sequentially transferred between SH groups
of ENZ 1 and ENZ 2 subunits
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 Lipids & Minerals

(2) Mitochondrial system

- Occurs in the mitochondria.
- Concerned with elongation of short and medium chain F.A into long chain F.A.
e.g. C10 or C12 to C20 , by addition of acetyl of β-oxidation working in the reverse
direction , except for acyl COA dehydrogenase reaction, which is Irreversible.
- It is reversed by Reductase, with NADPH2 as hydrogen donor.
(3) Microsomal system
- Occur in microsomes
- Concerned with Elongation of FA from C10 to C24
(II) Synthesis of glycerol
(1) Glycerol of the diet is activated

(2) α -glycerol phosphate can also be derived from Dihydroxy acetone phosphate of glycolysis .

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 Lipids & Minerals

(III) Synthesis of Triglycerides

 Most of these enzymes are present in microsomes but some are present in
mitochondria.
 Fatty acids are stored for future use as triacylglycerols (TAGs) in all cells, but
primarily in adipocytes of adipose tissue. TAGs constitute molecules of glycerol to
which three fatty acids have been esterified. The fatty acids present in TAGs are
predominantly saturated. The major building block for the synthesis of TAGs, in
tissues other than adipose tissue, is glycerol. Adipocytes lack glycerol kinase,
therefore, dihydroxyacetone phosphate (DHAP), produced during glycolysis, is the
precursor for TAG synthesis in adipose tissue.
 This means that adipocytes must have glucose to oxidize in order to store fatty
acids in the form of TAGs. DHAP can also serve as a backbone precursor for TAG
synthesis in tissues other than adipose, but does so to a much lesser extent than
glycerol.
 The glycerol backbone of TAGs is activated by
phosphorylation at the C-3 position by glycerol kinase. The
utilization of DHAP for the backbone is carried out through
either of two pathways depending upon whether the
synthesis of triglycerides is carried out in the mitochondria
and ER or the ER and the peroxisomes. In the former case
the action of glycerol-3-phosphate dehydrogenase, a
reaction that requires NADH (the same reaction as that used
in the glycerol-phosphate shuttle), converts DHAP to
glycerol-3-phosphate. Glycerol-3-phosphate acyltransferase
(GPAT) then esterifies a fatty acid to glycerol-3-phosphate
generating the monoacylglycerol phosphate structure called
lysophosphatidic acid.

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 Lipids & Minerals

 The second reaction pathway utilizes the peroxisomal enzyme DHAP

acyltransferase to fatty acylate DHAP to acyl-DHAP which is then reduced by the
NADPH-requiring enzyme acyl-DHAP reductase. An interesting feature of the latter
pathway is that DHAP acyltransferase is one of only a few enzymes that are targeted
to the peroxisomes through the recognition of a peroxisome targeting sequence 2
(PTS2) motifs in the enzyme. Most peroxisomal enzymes contain a PTS1 motif. For
more information on peroxisome enzymes.

 The fatty acids incorporated into TAGs are activated to acyl-CoAs through the
action of acyl-CoA synthetases. Two molecules of acyl-CoA are esterified to
glycerol-3-phosphate to yield 1,2-diacylglycerol phosphate (commonly identified as
phosphatidic acid). The phosphate is then removed, by phosphatidic acid phosphatase
(PAP1), to yield 1,2-diacylglycerol, the substrate for addition of the third fatty acid.
Intestinal monoacylglycerols, derived from the hydrolysis of dietary fats, can also
serve as substrates for the synthesis of 1,2-diacylglycerols.

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Lipids & Minerals

Quiz 4

1. De novo synthesis of fatty acids is catalysed by a multi-enzyme complex which contains

(A) One-SH group (B) Two-SH groups
(C) Three-SH groups (D) Four-SH groups

2. NADPH required for fatty acid synthesis can come from

(A) Hexose monophosphate shunt (B) Oxidative decarboxylation of malate
(C) Extramitochondrial oxidation of isocitrate (D) All of these

3. The key enzyme in the regulation of fatty acid synthesis is

A. acetyl CoA carboxylase

B. AMP activated proteinkinase

C. protein phosphatase

D. none of these

4. In synthesis of Triglyceride from α-Glycero phosphate and acetyl CoA, the first
intermediate formed is
(A) β-diacyl glycerol (B) Acyl carnitine
(C) Monoacyl glycerol (D) Phosphatidic acid

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 Lipids & Minerals

Ketone Bodies Metabolism

Ketogenesis
• Definition: It the synthesis of KB from acetyl-CoA resulting from oxidation of
fatty acids. Ketone bodies are acetoacetic acid; b-hydroxybutyric acid and acetone.
• Site: Only in the mitochondria of the liver.
• Importance: KB is important source of energy for the peripheral tissues during
fasting.
Regulation:
• Ketogenesis is increased during fasting and starvation because there is decreased
blood glucose and insulin and increased anti-insulin hormones (glucagon, adrenaline,
glucocorticoids, growth hormone, & thyroxin), which stimulate lipolysis in adipose
tissue and b-oxidation of FA in liver.

• Ketogenesis is inhibited after CHO feeding because there is increased blood

glucose and insulin, which inhibits lipolysis in adipose tissue and b-oxidation of FA
in liver.

Ketolysis
 Definition: It is the complete oxidation of ketone bodies to CO2, H2O and energy.
• Site: It occurs in the mitochondria of the extra-hepatic tissues (e.g. muscles,
kidneys, lungs, brain). It never occurs in the liver.
Importance: It provides a good part of energy required during fasting by the
peripheral tissues.
• Regulation: Ketolysis is increased by insulin H. & decreased by anti-insulin H.
(glucocorticoids, glucagon & adrenaline).

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 Lipids & Minerals

Fatty acyl-CoA
Liver mitochondria
b- Oxidation

CH3 CO CH2 CO SCOA CH3 CO SCOA CH3 CO CH3

Acetoacetyl-CoA Acetyl-CoA Acetone

HMG-CoA
Synthase

OH
HOOC CH2 C CH2 CO SCOA CH3 CO CH2 COOH
CH3 HMG-CoA
Acetoacetate
HMG-CoA Lyase NADH
b-Hydroxybutyrate
Dehydrogenase
NAD+
OH
b-Hydroxybutyrate CH3 CH CH2 COOH

Blood Ketone bodies

Ketone body utilization

In
M uscle, Kidney b-Hydroxybutyrate
+
and Brain NA D

NA DH Thiolase
Acetoacetate Acetoacetyl CoA 2 Acetyl-CoA

Thiophorase
3 ATP

Succinyl-CoA succinate
TCA
Ketone body synthesis and utilization

Ketone Body Oxidation

 High rates of lipolysis (e.G., Long-term starvation or in uncontrolled diabetes)
produce sufficient ketones in the blood to be effective as a fuel
 Ketones are the preferred fuel if glucose, ketones, fatty acids all available in the
blood
 Primary tissues: using ketones, when available, are brain, muscle, kidney and
intestine, but NOT the liver.
 b-Hydroxybutyrate + NAD+  acetoacetate + NADH
 b-hydroxybutyrate dehydrogenase in mitochondria; reverse of ketogenesis

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 Lipids & Minerals

Why Ketogenesis occurs in liver while Ketolysis does not?

 Ketogenesis occurs in liver only because it is the only tissue that contains HMG-
CoA Synthase and HMG-CoA Lyase (3-hydroxy-3-methyl-glutaryl-CoA) enzymes.
Other tissues do not contain these enzymes.
 Ketolysis DOES NOT occur in liver because it does not contain Thiophorase
enzyme. Other tissues contain Thiophorase enzyme.
KETOACIDOSIS
 Excessive build-up of ketone bodies results in ketosis eventually leading to a fall
in blood pH due to the acidic ketone bodies.

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Lipids & Minerals

Quiz 5
Ketosis in partly ascribed to
(A) Over production and Glucose
(B) Under production of Glucose
(C) Increased carbohydrate utilization
(D) Increased fat utilization
All the following statements regarding ketone bodies are true except
(A) They may result from starvation
(B) They are formed in kidneys
(C) They include acetoacetic acid and acetone
(D) They may be excreted in urine

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 Lipids & Minerals

Lipoproteins Metabolism
Plasma lipoproteins:
For triacylglycerol transport (TG-rich):
- Chylomicrons: TG of dietary origin
- VLDL: TG of endogenous (hepatic) synthesis
For cholesterol transport (cholesterol-rich):
LDL: Mainly free cholesterol
HDL: Mainly esterified cholesterol
Metabolism of Chylomicrons
 Transport dietary TG and Cholesterol from the intestine to the peripheral tissues
 The dietary TG are first acted by intestine lipase and absorbed as
monoacylglycerol, fatty acid and glycerol. Within the intestine cells, they are
resynthesized into TG.
 CM are synthesized in the intestine using TG, PL, C, ApoB48, and ApoAs and
secreted into the lymph and reach blood through thoracic duct.
 Nascent CM picks up apoE, apoCs and some apoAs from HDL.
 In the capillaries of peripheral tissue, lipoprotein lipase (LPL) degrades triglycerol
(TG) of chylomicrons to fatty acids (FA) and glycerol which enter tissues by
diffusion
 Lipoprotein lipase (LPL) is activated by apo C-II
 After most of the TG is removed, chylomicrons become chylomicron remnants.
During the process, CM gives apoC and apoA to HDL.
 CM remnants bind to specific receptors on the surface of liver cells through apo E
and then the complex is endocytosed.
 remnant receptor or
 apoE receptor or
 LRP (LDL receptor-related protein)

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 Lipids & Minerals

 Chylomicron remnants deliver dietary cholesterol and some cellular cholesterol

(via HDL) to the liver.
 Half life of CM is short, less than 1 hour.

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 Lipids & Minerals

Metabolism of VLDL
 In the capillaries of various tissues, LPL degrades TG to fatty acids and glycerol,
which enter the tissues by diffusion. ApoC-II is needed in this step to activate LPL.
 When VLDL loses triglyceride, it transforms into VLDL remnant, also named as
IDL (intermediate-density lipoprotein).
 During the process, some apolipoproteins (apo As and apoCs) are transferred back
to HDL.
 VLDL function: Deliver TG from liver to peripheral tissue cells.

Fates of VLDL remnants (IDL):

 Results from loss of TG in VLDL
 Contains relatively more cholesterol esters
 Taken up by liver or transform into LDL
1) A proportion of the VLDL remnant (IDL) is taken up by liver through the LDL
receptor (apoE-mediated).
2) The other remnant is further acted upon by hepatic lipase (HL) and converted
into LDL. LDL loses all apolipoproteins except apoB100.

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 Lipids & Minerals

Low density lipoprotein

 LDL carries about 70% of total plasma cholesterol
 High LDL-C level is well established risk factor for development of coronary heart
disease
 The diagnosis of a primary defect is made after secondary defect causes have been
ruled out.
 Produced in the circulation as the end product of VLDLs
Compared to VLDLs:
 It contains only apo B-100
 Smaller size and more dense
 Less TG
 More cholesterol & cholesterol ester
 Transport cholesterol from liver to peripheral tissues
Uptake of LDL at tissue level by
 LDL receptor-mediated endocytosis
 Recognized by apo B-100

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 Lipids & Minerals

Receptor-mediated Endocytosis
LDL receptor:
Cell surface glycoprotein
High-affinity, tightly regulated
LDL/Receptor binding and internalization of the complex by endocytosis
Release of cholesterol inside the cells for:
Utilization
Storage as cholesterol ester
Excretion
Degradation of LDL: into amino acids, phospholipids and fatty acids
Degradation or recycling of receptor
LDL Receptor-Mediated Endocytosis: Regulation
Down-regulation:
High intracellular cholesterol content
Degradation of LDL receptors
Inhibition of recepotor synthesis at gene level
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 Lipids & Minerals

Decrease No. of receptor at cell surface

Decrease further uptake of LDL
Decrease de novo synthesis of cholesterol
Up-regulation:
Low intracellular cholesterol content
Recycling of LDL receptors
Stimulation of receptor synthesis at gene level
Increase No. of receptor at cell surface
Increase further uptake of LDL
Increase de novo synthesis of cholesterol
• Plasma LDL can be measured by ultracentrifugation, but this is not a practical
technique
• Calculated LDL:
Friedewald equation:
[LDL-chol] = [Total chol] - [HDL-chol] - ([TG]/5))
 LDL exits in a range of sizes & densities which can be detected by electrophoresis.
 There is evidence that small dense LDL is atherogenic

Coronary Heart Disease Risk Factors

Positive Risk Factors:
 Age ≥ 45 y for men , ≥55 y for females or premature menopause
 Family history of premature CHD
 Current cigarette smoking
 Hypertension ( BP≥ 140/90 or taking antihypertensive drugs
 HDL-C concentration < 40 mg/dL ( < 1.0 mmol/L)
 Diabetes mellitus = CHD risk equivalent
 Metabolic syndrome (multiple metabolic risk factors

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 Lipids & Minerals

Negative Risk Factors:

 HDL-C concentration ≥ 60 mg/ dL (≥ 1.6 mmol/L); its presence removes one risk
factor from the total count.

High Density Lipoproteins (HDL)

 Produced by intestine and liver
 Nascent HDL:
Disk-shaped
Contains apo A-I, C-II and E
Contains primarily phospholipid (PC)
 Mature HDL (HDL2):
First, the HDL3 collects cholesterol (C)
Then, C is converted to CE (C- ester)
The HDL2 is the spherical mature particle

Functions of HDL
 Reservoir of apoproteins: e.g., Apo C-II and E to VLDL.
 Uptake of cholesterol: From other lipoproteins & cell membranes. (HDL is suitable
for uptake of cholesterol because of high content of PC that can both solubilizes
cholesterol and acts as a source of fatty acid for cholesterol esterification)
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 Lipids & Minerals

 Esterification of cholesterol:
Enzyme: PCAT/LCAT, Activator: Apo A-I , Substrate: Cholesterol, Co-substrate:
PC, Product: Cholesterol ester (& Lyso-PC)

 Reverse cholesterol transport

Why Is HDL a Good Cholesterol carrier?

Inverse relation between plasma HDL levels and atherosclerosis …. How?

 Reverse cholesterol transport involves:

Efflux of cholesterol from peripheral tissues and other lipoproteins to HDL3

 Esterification of cholesterol & binding of HDL2 to liver and stroidogenic cells by

scavenger receptor class B (SR-B1)
 Selective transfer of cholesterol ester into these cells
 Release of lipid-depleted HDL3

Cardiac Risk Ratios

 The cardiac risk ratio provides more information than does either value alone. The
higher the ratio, the greater the risk for developing atherosclerosis.

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Types of hyperlipoproteinemia:
Type I: Familial lipoprotein lipase deficiency:
This type may be due to deficiency in lipoprotein lipase enzyme, occur after fatty
meal and is characterized by markedly increased chylomicrons due to very slow
clearing of chylomicrons from the blood.Reducing the amount of fat in diet may
correct the condition.
Type II:(familial hypercholesterolaemia or hyperB-lipoproteinaemia):
It is due to a defect in LDL receptors characterized by:
LDL (B-lipoprotein) are increased which is associated with increased plasma total
cholesterol. Lipid deposition in the tissue is common. Atherosclerosis.
Hypothyroids is associated with this type
Reduction of dietary cholesterol and saturated fats may be used in treatment.
3) Type III (hyper lipoproteinaemia, broad B-diseaase or remnants disease):
Characterized by:
LDL and VLDL (B-lipoproteins and pre B-lipo-proteins) are increased which are
associated with increased cholesterol and triglycerides.
Atherosclerosis of both peripheral and coronary arteries is common.
4) Familial hypertriacylglycerolaemia:
Characterized by:
High levels of VLDL (pre B-Lipoprotein) which is associated with increased
triacylglycerols of endogenous source (liver).
LDL and HDL (B-lipoprotein and x – lipoprotein) are subnormal in quantities.

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It is associated with coronary heart disease maturity onset diabetes, obesity with
progestational hormones.
Treated as type III.
5) Type V Familial hyperlipopteinaemia
Characterized by:
1- Chylomicrons and VLDL (pre B-lipoproteins) are elevated which are associated
with increased plasma triacylglycerol and cholesterol.
2- It is usually associated with obesity.
3- Treatment: by weight reduction
II- Hypolipoproteinaemia :
1- Abetalipoproteinaemia:
Rare inherited disease characterized by:
1- Absence of chylomicrons, VLDL, LDL.
2- Most of blood lipids are present in low concentration.
2) Familial hypobeta lipoproiteinaemia:
Characterized by:
1- LDL (B-lipoprotein) concentration is between 10-50% of normal.
3) Familial α – Lipoprotein deficiency:
Characterized by:
1-Absence of plasma HDL (α – lipoproteins) which is associated with accumulation
of cholesterol esters in the tissue.

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Cholesterol Metabolism
Cholesterol is an animal sterol.
Source:
1- Endogenous: Cholesterol is formed in the body in the liver from active acetate
1g/day.
2- Exogenous:
 It is a product of animal metabolism which occurs only in foods of animal origin
such as egg yolk, meat, brain x liver (most rich Sources) giving an average supply of
about 0.5 gm/day.
 The liver plays an important role in the regulation of the body's cholesterol
homeostasis. For example cholesterol enters the livers cholesterol pool from a
number of sources including dietary cholesterol, as well as cholesterol synthesized de
novo by extra-hepatic tissue as well as the liver tissue itself.
 Cholesterol is eliminated from the liver as unmodified cholesterol in the bile, or it
can be converted into bile salts that are secreated into the intestinal lumen. It can also
serve as a component of plasma lipoprotein sent to the peripheral tissue.
 In humans, the balance between cholesterol influx and efflux is not precise,
resulting in a gradual deposition of cholesterol in tissue particularly in the endothelial
lining of blood vessels. This is a potentially life threatening occurrence when the lipid
deposition lead to plaque formation, causing narrowing of blood vessels
(atherosclerosis) and increased risk of coronary artery disease (CAD).
Structure of cholesterol:
Cholesterol is a very hydrophobic Compound. It consist of 4 fused hydrocarbon
rings (A,B, C x D called steroid nucleus) and an 8 – carbon branched hydrocarbon
attached to C17 of D ring and a hydroxyl group at C3 of ring A and a double bond
between C6 – C5 of ring B.
Function:
1- Cholesterol enters in the structure of everybody cell.

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2- Cholesterol is a precursor of vitamin Δ3.

3- It is the precursor of steroid hormones.
4- It is the precursor of bile salts.
Synthesis of cholesterol:
Site:
The main site for cholesterol synthesis is the liver, other tissues for cholesterol
synthesis include:
- Adrenal cortex (glucocorticoids).
- Skin 7 dehydrocholesterol.
- Testis testosterone.
- Intestine.
- Ovaries.
Note:
All tissues can synthesize cholesterol for their need only but the liver is the source of
cholesterol in blood.

Steps of cholesterol synthesis:

The process of cholesterol synthesis has five major steps:

1. Acetyl-CoAs are converted to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)

2. HMG-CoA is converted to mevalonate

3. Mevalonate is converted to the isoprene based molecule, isopentenyl

pyrophosphate (IPP), with the concomitant loss of CO2

4. IPP is converted to squalene

5. Squalene is converted to cholesterol.

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Reactions of cholesterol synthesis:

Hydroxymethylglutaryl-coenzyme A (HMG-CoA) is the precursor for cholesterol

synthesis. HMG-CoA is also an intermediate on the pathway for synthesis of ketone
bodies from acetyl-CoA. The enzymes for ketone body production are located in the
mitochondrial matrix. HMG-CoA destined for cholesterol synthesis is made by
equivalent, but different, enzymes in the cytosol.
 HMG-CoA is formed by condensation of acetyl-CoA & acetoacetyl-CoA,
catalyzed by HMG-CoA Synthase.
 HMG-CoA Reductase catalyzes production of mevalonate from HMG-CoA.

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 The carboxyl of HMG that is in ester linkage to the CoA thiol is reduced to an
aldehyde, and then to an alcohol.
 NADPH serves as reductant in the 2-step reaction.
 Mevaldehyde is thought to be an active site intermediate, following the first
reduction and release of CoA.

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 HMG-CoA Reductase is an integral protein of endoplasmic reticulum

membranes.

 The catalytic domain of this enzyme remains active following cleavage from the
transmembrane portion of the enzyme.
 The HMG-CoA Reductase reaction, in which mevalonate is formed from HMG-
CoA, is rate-limiting for cholesterol synthesis.
 Mevalonate is phosphorylated by 2 sequential Pi transfers from ATP, yielding the
pyrophosphate derivative.
 ATP-dependent decarboxylation, with dehydration, yields isopentenyl
pyrophosphate.
 Isopentenyl pyrophosphate is the first of several compounds in the pathway that
are referred to as isoprenoids, by reference to the compound isoprene.
 Isopentenyl Pyrophosphate Isomerase inter-converts isopentenyl pyrophosphate
& dimethylallyl pyrophosphate.

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Mechanism: protonation followed by deprotonation.

Prenyl Transferase catalyzes head-to-tail condensations:
 Dimethylallyl pyrophosphate & isopentenyl pyrophosphate react to form geranyl
pyrophosphate.
 Condensation with another isopentenyl pyrophosphate yields farnesyl
pyrophosphate.
 Each condensation reaction is thought to involve a reactive carbocation formed as
PPi is eliminated.
 Head-to-head condensation of 2 farnesyl pyrophosphate, with reduction by
NADPH, yields squalene.
 Squaline epoxidase catalyzes conversion of squalene to 2, 3-oxidosqualene.
 This mixed function oxidation requires NADPH as reductant & O2 as oxidant. One
O atom is incorporated into substrate (as the epoxide) & the other O is reduced to
water.
 Squalene Oxidocyclase catalyzes a series of electron shifts, initiated by
protonation of the epoxide, resulting in cyclization. The product is the sterol
lanosterol
 Conversion of lanosterol to cholesterol involves 19 reactions, catalyzed by
enzymes in ER membranes.
Regulation of cholesterol synthesis : -
MMGR- COA reductase, the rate limiting enzyme, is the major control point for
cholesterol biosynthesis. This enzyme is inhibited by cholesterol and stimulated by
fasting.
It is affected by different metabolic control as:
1- Repression of the synthesis of new reductase
2- Induction of the synthesis of enzymes that destruct reductase.
3- Feedback inhabitation.

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4- Hormonal regulation: where insulin increases cholesterol synthesis by activation of

reductase enzyme while glucagon inhibits it.
5- Inhibition by drugs: the statin drugs are structural analogs of HMG COA and are
reversible competitive inhibitors of HMG COA reductase thus used to decrease
plasma cholesterol levels in patients with hypercholesterolimia.
Degradation of cholesterol : -
* The ring structure of cholesterol cannot be metabolized to co 2 and H2o in human
thus eliminated from the body by conversion to bile acids and bile salts, which are
transported to the intestine and execrated in faces.
* Some cholesterol in the intestine is modified by bacteria (reduced) to coprostanol
and cholestanol before execrated.
Hypercholesterolemia:
It is the decrease in blood cholesterol level due to:
1- Dietary:
* Starvation inhibit HMG-COA reductase enzyme
* Diet of low cholesterol, saturated fatty acid and carbohydrates rich in poly
unsaturated fatty acid.
2- Liver diseases:
* Hepatocellular damage is associated with hypercholesterolemia due to decrease in
synthesis.
3- Server anemia:
* cause hypercholesterolemia of unknown cause.
4- Hyperthyroidism: -
* Cause hypercholesterolemia due to increased cholesterol oxidation to bile acids.
5- Infection:
E.g: tuberculosis causes hypercholesterolemia for unknown cause.
Hypercholesterolemia:
It is the increase in blood cholesterol level due to:

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1- Diet:
* Diet rich in saturated fatty acids and carbohydrates which may lead to:
- increase HMG-COA reductase activity.
- Excess formation of acetyl COA
2- Diabetes mellitus: Due to excess active acetate and activation of HMG-COA
reductase.
3- Hypothyroidism: Due to decreased oxidation of cholesterol to bile acids.
4- Familial Hyperlipoproteinemia.
5- Obstructive jaundice: due to blockage of main way of execration of cholesterol from
the body.
6- Nephrosis: due to unknown cause.
Cholesterol and atherosclerosis :
 Atherosclerosis is characterizes by the deposition of cholesterol esters and other
lipids in the connective tissue of the arterial walls.
 Any disease which causes prolonged hyperlipidemia as diabetes mellitus or
hypothyroidism is often accompanied by severe atherosclerosis.

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Quiz 6

Cholesterolemia means
A. lack of functional LDL receptors

B. lack of functional HDL receptor

C. high sensitivity to fatty food intake

D. none of the above

VLDLs are synthesized in

A. blood B. liver

C. intestine D. pancreas

Chylomicrons are synthesized in

A. blood B. liver

C. intestine D. pancreas

How many types of lipoproteins are there?

A. 2 B. 6

C. 8 D. 5
Statins are drugs taken to lower blood cholesterol. What is their mode of action?
a) They activate hormone sensitive lipase.
b) They inhibit lipoprotein lipase.
c) They inhibit HMG CoA reductase.
d) They inhibit lecithin-cholesterol acyl transferase.

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Phospholipids metabolism
 Phospholipids are synthesized in all tissues. All tissues synthesize their
requirements only of phospholipids, except liver synthesize its requirements and also
passes its phospholipids to blood and to tissues. So, liver is the only source of blood
phospholipids.
 Phospholipids are a class of lipids that are a major component of all cell
membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride,
a phosphate group, and a simple organic molecule such as choline; one exception to
this rule is sphingomyelin, which is derived from sphingosine instead of glycerol.
 The structure of the phospholipid molecule generally consists of hydrophobic tails
and a hydrophilic head. The phospholipids are not "true fats" because they have one
of the fatty acids replaced by a phosphate group.
Function:
1- They enter in the structure of cell membrane
and of cell its permeability.
2- Phosphatidyl serine and ethanolamine enter
in the formation of thromboplastin which is a
substance necessary for blood coagulation.
3- They are important for some enzymatic
reactions e.g. cytochromes.
4- Sphingomyelin acts as electric insulator, so
plays a role in nerve impulse conduction.
Properties of phospholipids:
• Phospholipids are amphipathic molecules
• Head group = alcohol attached via phosphodiester linkage to either:
Diacylglycerol (glycerophospholipid) or sphingosine (sphingophospholipid =
sphingomyelin).

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Site of phospholipids synthesis:

Although all tissues synthesize phospholipids, all tissues except liver synthesize their
requirement only phospholipids but the liver synthesize its requirement and also pass
its phospholipids to blood and other tissues. So liver is the only source of blood
phospholipids.
Types of phospholipids:
Glycerophospholipid:
• The simplest glycerophospholipid is phosphatidic acid
(PA)
• It consists of glycerol, phosphate, and 2
fatty acyl chains in ester linkages
Other glycero-phospholipids derived from PA
include:

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Plasmalogens
• Plasmalogens have an ether-linked hydrocarbon chain at C-1
of glycerol, instead of ester-linked fatty acid
• Platelet-activating factor (PAF) is a plasmalogen (a
phosphatidylcholine) with an acetyl group at C-2 of glycerol
• It has potent physiologic actions (platelet activation;
inflammatory responses; broncho-constriction.
Sphingolipids:
• Sphingomyelin contains sphingosine with a long-chain fatty acid attached in amide
linkage ( = ceramide)
• Ceramide plus a phosphocholine group constitutes a sphingomyelin
• Ceramide is also the core component of glycosphingolipids.
Note : We will study sphingomyelin as an example

Sphingomyelin
• Sphingomyelin is present in plasma membranes and in lipoproteins
• It is very abundant in myelin
• Sphingomyelin is abundant in specialized plasma membrane microdomains called
lipid rafts.

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Structure:
1. Sphingosine base 3- Phosphate
2. Fatty acid 4- Choline
Note:
• Sphingomyelin of the myelin sheath (a
structure that insulate and protects neuronal
fibers of the central nervous system)
contains predominately longer – chain fatty
acids such as legnoceric and nervonic acids,
while gray matter of the brain has
sphingomyelin that contains primarily stearic acid.
Synthesis of sphingomyelin:
Sphingomyelin is made from:
Palmitoyl CoA + serine sphingosine
Sphingosine + FA CoA ceramide
Ceramide + CDP-choline sphingomyelin
FA’s are commonly 18:0, 24:0, and 24:1 (15)

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Degradation of sphingomyeline : -
* Sphingomyelin is degraded by sphingomyelinase, a lysosomal enzyme that
hydrolytically removes phosphoryl choline, leaving a ceramide.
* The Ceramide is, in turn, cleaved by ceromidase into sphingosine and a free fatty
acid.

Niemann-Pick disease:
* A genetic disease caused by the inability to degrade Sphingomyelin due to deficient
in sphingomyelinase enzyme.
* In severe cases, the liver and spleen (sit of lipid deposits) are tremendously
enlarged.

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Infants with such disease suffer server mental retardation and death in early
childhood.
Lecithin:
- It is a phosphatidyl choline
- It is formed of "Glycerol saturated F.A., unsaturated F.A., (P) and choline base ".
- It is present in 2 forms α and β forms.

Biosynthesis:
1- Biosynthesis of 1,2 diacylglycerol

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2- Activation of choline to CDP- choline:

3- Biosynthesis of lecithin:

Cephalins:
-Chepalin is phosphatidyl ethanolamine phosphatidyl serine or phosphatidyl inositol.
- Exactly the same steps but we use :
Active ethanolamine (CDP- ethanolamine), CDP – serine of CDP inositol.
-And the enzymes are phospho ethanolamine-diacylglycerol transferase, phospho
serine diacylglycerol transferase or phosphoinsitol diacylglycerol transferase.

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Relationship between colamine , ethyl alcohol and serine :

Degradation and turnover of phospholipids :

There is an enzyme called phospholipase, which causes partial degradation followed
by re-synthesis.
- An alternative way for lyso-lecithin formation lyso-lecithin be formed by the action
of lecithin cholesterol acyl transferase (LCAT). This enzyme is present in liver and
plasma and it transfers acyl residue at position 2 of lecithin to cholesterol.
LCAT
Lecithin + cholesterol lysolecithin + cholesterol ester
- Continuous exchange of F.A. between cholesterol esters and lysolecithin is
responsible for introducing essential F.A. into
phospholipids molecule again.

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Part II. MINERALS AND WATER

METABOLISM
 Introduction:
More than one-third of the dietary nutrients needed for a healthy body are
minerals. Seventeen minerals are among the nearly 45 dietary nutrients known to be
necessary for life and account for four percent of body weight. The mineral
composition of the human body is seen in the following figure. The "other" category
includes potassium, sodium, sulfur, chlorine, iron, zinc, magnesium, iodine and other
trace minerals. Although minerals represent only a very small fraction of human body
weight, they play important roles in all areas of the body. They help form bones and
teeth, aid in normal muscle and nerve activity, act as catalysts in many enzyme
systems, help control water levels in the body and are components of such
compounds in the body as hemoglobin and the hormone thyroxine. Evidence is
mounting that certain minerals like calcium and selenium may help prevent cancer.
And that deficiencies of zinc may decrease the ability of the immune system to
function. A condensed summary of minerals is attached.

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Lipids & Minerals

Minerals that are essential to the body fall under one of two
categories, major and minor.
1. Major minerals are needed in amounts greater than 100 mg/day and include
calcium, phosphorus, magnesium, sodium, chloride, potassium, and sulfur. Sodium,
chloride and potassium are also known as body electrolytes. Sulfur is a part of the
essential amino acid, methionine so is easily obtained by eating protein rich foods.
2. Minor minerals are trace elements needed in amounts of less than a few mg/day
and include iron, zinc, iodine, fluoride, copper, selenium, chromium, cobalt,
manganese and molybdenum. Iron, zinc, selenium and iodine are the only minor
minerals that have been studied sufficiently to establish required dietary amounts
(RDA). For the remainder with the exception of cobalt, safe and adequate daily
ranges have been estimated by the Food and Nutrition Board of the National
Academy of Sciences. There are several minerals that may be essential for humans,
but research has not established their importance, including tin, nickel, silicon and
vanadium. There are also other minerals found in the body that are regarded as
contaminants including lead, mercury, arsenic, aluminum, silver, cadmium, barium,
strontium and others.

Major -Minerals
(1) Calcium
Calcium is a key nutrient in the human body. The primary emphasis on calcium
consumption during its initial scientific discovery was focused on early human life
primarily during growth periods of infancy and childhood.
The interest on calcium requirements during the last decade has been expanded to
apply to the entire life cycle from birth through elder years. Many commercial food
and nutrition supplement products contain calcium fortification today in response to a
wider audience.
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Lipids & Minerals

The role of calcium in human health

 Calcium as a key nutrient
Calcium is the most abundant stored nutrient in the human body. More than 99%
(1.2-1.4 kg) is stored in the bones and teeth. Less than 1% is found in extracellular
serum calcium.
When adults consume calcium as food or supplements, the average absorption rate is
approximately 30%. The rate can vary widely due to multiple factors. For example, in
pregnancy when more calcium is required for the growing fetus the calcium
absorption rate increases
 Calcium distribution in the body
Calcium is distributed among various tissue compartments
in the human body. The total serum pool of calcium, approximately 1,200-1,400 mg,
is very small. This extracellular pool maintains the plasma calcium level in tight
control at a constant serum level (typically 8.4-9.5 mg/dL) using a complex team of
hormones and other substances. An example of another tight metabolic control
mechanism system in the human body would be the maintenance of a normal serum
glucose range in non-diabetics.
Serum calcium does not fluctuate with changes in dietary intake. The smallest drop in
serum calcium below the normal level will trigger an immediate response. The body
is ready to transfer calcium from other sources to maintain normal serum calcium
levels and prevent hypocalcemia usually within minutes using one of three organ
systems. Thus, serum calcium is not an accurate indicator of calcium stores in the
body.
The three organ systems are the kidney, the intestines, and the bone. The kidney is
the primary mechanism for rapid release or absorption of calcium through the
filtration and urine excretion functions. Approximately 200 mg per day is typically
excreted by adults through the kidneys via urine but varies by diet and serum
parameters. The second organ system, the intestines, is slower in response. A daily
dietary intake of 1,000 mg of calcium would potentially result in 800 mg available for
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Lipids & Minerals

tissue nutrient requirements and 200 mg to maintain serum calcium levels. Extra
intestinal calcium can be processed through the kidneys and removed from the body
through urinary excretion. In the third system, calcium can move both into and from
bone matrix. The flexible bone pool, which varies by body size and bone density,
typically has available calcium of approximately 150-200 mg. If more is required,
actual bone calcium must be released (―borrowed‖) from the bone matrix and used to
maintain serum calcium. Replacement of ―borrowed‖ calcium does not always insure
similar bone composition.
 Function of calcium
Calcium is used throughout the body in small amounts. Research has confirmed that
calcium is involved in vascular contraction, vasodilation, muscle functions, nerve
transmission, intracellular signaling, and hormonal secretion. Each one of these
functions could comprise a separate review in itself but as a group illustrate how
essential calcium is in the human body. Any change in serum calcium affects one or
more of these functions. For example, hypocalcemia has been linked to higher risk of
seizures due to its relationship with nerve transmission and intracellular signaling.
 Metabolic aspects of calcium absorption
Calcium absorption occurs throughout the gastrointestinal tract but varies by region.
The majority of the calcium, approximately 65%, is absorbed where the pH is 6.5-
7.5. In the ileum, the primary mechanism is passive absorption as the food moves
slowly through this area of the gastrointestinal tract. It is important to note that
calcium is not absorbed in the stomach.
The total amount of calcium that is absorbed compared to what is available is
dependent on the quantity of calcium presented, the total and segmental transit time,
and the amount of calcium that is present in each unique pH environment. The
solubility of calcium supplements are directly affected by the pH level.

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Lipids & Minerals

 Homeostasis of calcium
Human body contains about 1,000 g of calcium. Vast majority (98 – 99 %) of this
amount is built in the hard tissues such as bones and teeth; the rest is located outside
bones, largely extracellularly.
Calcium is released from the hard tissues in response to body needs. Very small
amount of calcium is found in intracellular fluid. Inside the cell, 55 % of calcium is
located in the endoplasmic reticulum, the rest in other cell organelles. Concentration
of Ca2+ in the cytosol (10−7 mol/l) is four orders of magnitude lower than its
concentration in blood plasma (10−3 mol/l); and this steep gradient between extra-
and intracellular fluid is kept by many membrane transport mechanisms. Transient
elevations of Ca2+ in the cytosol represent important signals for the cell, mediating
the whole array of cellular functions and events (e.g. muscle contraction,
transmission of nerve excitation, secretion of hormones, cell division).
The dietary intake of calcium fluctuates around 1 g per day; in the periods of
increased demand (growth, pregnancy, lactation) it can be as much as 1.5 g. Under
physiological condition about 25- 40 % of ingested calcium is absorbed in the small
intestine. From the extracellular fluid the calcium passes mainly to bones where it
becomes a substantial component of bone mineral. Exchange between bone tissue
and extracellular fluid helps to regulate calcemia. Excretion of calcium takes place in
the intestine (80%) and kidney (20%).
The renal excretion critically affects calcium balance in the body. In an adult, intake
of calcium normally balances its excretion. Positive calcium balance is characteristic
for childhood and adolescence, while in women after menopause and advanced age in
general a negative calcium balance is found. Level of calcium in the blood is
regulated by parathyroid hormone, 1,25- dihydroxycholecalciferol (calcitriol) and
calcitonin.

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Lipids & Minerals

Fig. 2 Daily calcium balance

Fig. 3 Regulation of calcium homeostasis

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Lipids & Minerals

 Calcium in serum
Estimation of serum calcium represents a basic screening examination for assessment
of calcium homeostasis.
Calcium in serum exists in several forms:
• 60 % of total calcium is diffusible – filtered by renal glomeruli. From this fraction:
- 50 % of total calcium is in free (ionized) form (denoted as Ca2+). This is the
biologically active form of calcium.
- 10 % of total calcium occurs in low-molecular-weight complexes with citrate,
phosphate or hydrogen carbonate
• 40 % of total calcium is not diffusible (does not pass the glomerular membrane) as
it is bound to plasma proteins (albumin - 90%, globulins - 10 %). The protein-bound
calcium is not biologically active, but rather it represents a readily accessible reserve
from which calcium can be quickly released during hypocalcemia. In
hypoalbuminemia the calcium fraction bound to albumin decreases. Drop of
plasmatic albumin of 10 g/l makes the total serum calcium level 0.2 mmol/l lower
without any effect on the plasma concentration of ionized calcium. On the other hand,
hyperproteinemia (e.g. in malign myeloma) may lead to a high increase in total
calcemia, again without change in ionized calcium level.
Therefore, both parameters, i.e. serum calcium and albumin, should be considered
together. The amount of Ca2+ depends on pH: it decreases in alkalosis and increases
in acidosis, due to mutual competition of Ca2+ and H+ ions for the binding sites on
albumin.

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Lipids & Minerals

Fig. 4 Forms of calcium in serum

 Calcium in urine
The diffusible (ultrafiltrable) fraction of serum calcium in renal glomeruli passes into
primary urine; subsequently in the tubules 98-99 % of this amount is reabsorbed, and
the rest is excreted into urine.
Amount of calcium in the urine (calciuria) depends on:
• Dietary contents of calcium and its absorption in the intestine
• Degree of osteoresorption
• function of renal tubules

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 Lipids & Minerals

(2) Phosphorus
Phosphorus sources
Phosphorus (P) is abundant in many food sources, as foods can contain both natural
P and phosphate additives. Foods high in protein are also high in natural P. In
Finland, the main dietary sources of P are dairy, grain and meat products. The P
content of foodstuffs varies between 0 and 1570 mg/100 g of product (National
Institute for Health and Welfare 2009). In some countries, dietary supplements may
also contain P as phosphates. Protein bars and products used to build muscle mass
may have high P content.

Table 3: Phosphorus (P) content of selected foods.

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Lipids & Minerals

Phosphorus in the human body

After oxygen, hydrogen, carbon, nitrogen and Ca, P is the 6th most abundant element
in the human body. A 70-kg man has approximately 700 g of P in his body. Around
80-85% of the P is located in the skeleton as hydroxyapatite (Ca10(PO4)6(OH)2). The
remaining P is located in extracellular fluids and soft tissues, mainly as a component
of proteins, phospholipids, nucleotides and nucleic acids. Besides being an essential
nutrient in bone mineralization, P has many other vital functions in the human body;
it is involved in energy metabolism, cellular signalling through phosphorylation and
is a structural part of phospholipids, nucleotides and nucleic acids. Intracellular
phosphate is present in a variety of phosphorylated compounds, such as adenosine
triphosphate (ATP) and guanosine triphosphate (GTP), which are fundamental in
energy metabolism and enzyme activation. Phosphorus also serves as an extra- and
intracellular buffer through the interconversion of HPO4 2- and H2PO4 -, thus helping
to maintain normal pH.
In living tissues, P exists in the form of phosphate (PO4 3-). Most of the P in whole
blood is in the phospholipids of red blood cells and plasma lipoprotein, and only ~1
mmol/l is found as inorganic Pi, which can be in different forms, the most common
being HPO4 2-. Inorganic Pi is measurable by laboratory measurements from plasma
or serum samples. This fraction is an exchange pool between organs containing P
(intestine, bone, kidneys and cells), regulating P homeostasis.

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Lipids & Minerals

Figure 5. Distribution of phosphorus in the human body

Phosphorus homeostasis
The main P homeostasis regulation sites are the gastrointestinal tract (absorption
organ), kidneys (excretion organ) and bone (storage organ). The most important
regulation occurs in the kidneys, and homeostasis is achieved by excreting P in urine.
In healthy humans with normal dietary P intake, around 6-7 g of P is filtered daily by
the kidneys. More than 80% of P is reabsorbed in the proximal tubule and ~10% in
the distal tubule and ~10% is excreted in urine. The predominant regulators of renal
tubular Pi reabsorption are dietary P intake and S-PTH concentration.
Phosphorus in the human body is in balance when the output (loss of P in urine,
faeces and sweat) is equal to the absorbed amount of P (net intestinal absorption)

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Figure 6. Phosphorus homeostasis and balance in a normal adult

S-Pi concentration is kept within the normal range mainly by parathyroid
hormone (PTH) and 1,25(OH)2D (Berndt and Kumar 2008). When S-Pi decreases,
serum 1,25(OH)2D (S- 1,25(OH)2D) increases, which elevates P absorption in the
gut and release of P from bone. The elevated serum PTH (S-PTH) concentration
increases U-Pi excretion and release of P from bone (Fig. 3). The effect of

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1,25(OH)2D on U-Pi excretion is indirect; an increase in serum calcium (S-Ca)

concentration, which is mediated by 1,25(OH)2D, suppresses PTH secretion, which,
in turn, enhances Pi reabsorption, newly discovering signalling pathways involving P
regulation have been presented; a key role in P metabolism has been suggested for
Na-phosphate-cotransporters (NPTs), which are found in different tissues. Type 1 and
2 NPT proteins have been observed in the kidneys. A high-P diet decreases while a
low-P diet increases the number of NPT2a in the proximal tubule, the former
increasing U-Pi excretion.

Figure7. Regulation of phosphorus (P) metabolism in situations with high and

low dietary P intakes in healthy humans
Phosphorus in serum
The phosphorus exists in serum in two main forms:
• Organic phosphorus (about 70 %, mostly in phospholipids)
• Inorganic phosphorus (about 30 %, as phosphate1), most of which is free and only
to a small extent it binds to serum protein (unlike calcium) or to calcium and
magnesium. Only the inorganic phosphate is routinely estimated in clinical chemistry
laboratories. At the physiologic pH 7.4 the ratio between hydrogen phosphate
HPO42− and dihydrogen phosphate H2PO4− in serum is 4:1. Concentration of serum
phosphate depends on the function of parathyroid glands and the kidney (both
glomerular filtration and tubular reabsorption). Parathyroid hormone decreases renal
reabsorption of phosphate. Renal insufficiency in general results in elevation of
serum phosphate.

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Examples of Metabolic Bone Diseases

Metabolic bone diseases typically affect the bones as a whole. They are caused by
impairment in the organic component of bone tissue, the bone mineral, or both. The
most significant metabolic bone disease is osteoporosis, but osteomalacia is also
common.
Osteoporosis
Osteoporosis is characterized by a decay of bone mass (both organic and inorganic
bone components are decreased proportionally) and disorder of bone micro-
architecture, resulting in fragility and tendency to fractures. The decay of bone mass
is more severe than the one corresponding to the age, gender, and race of a given
individual.
The osteoporosis results from an imbalance between escalated bone resorption and
normal or decreased bone formation. Until the age of 50, contents and density of the
bone mass change little with age in both men and women. Later, however, in post-
menopausal women in connection to loss of ovarial activity, the bone resorption
prevails over bone formation, and this trend continues ever after. In men the bone
mass also decays with age, but with much slower rate, and therefore men are less
affected by osteoporosis and resulting fractures than women.
Markers of calcium and phosphate metabolism, together with bone
resorption/formation are examined. In post-menopausal women, endangered by
osteoporosis, typically increased markers of osteoresorption, unmatched by increased
bone formation, are found.
Osteomalacia and rachitis
Osteomalacia is characterized by a decrease in the mineral component of the bone,
due to a disorder in the mineralization process. High amount of osteoid (non-
mineralized organic matrix) that calcifies slowly or not at all is found. Rachitis
(rickets) is a specific term for an osteomalacia in children. Growth of bones is a
prerequisite for development of rachitis.

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Osteomalacia is most often caused by vitamin D deficiency, resulting from its lack in
the diet, or disorders of its digestion and absorption. Lack of sunshine, and diseases
of liver and kidney associated with impaired conversion of vitamin D to its active
metabolites, would also lead to osteomalacia.
Laboratory testing in osteomalacia typically shows:
• low calcemia, • low phosphatemia
• high catalytic concentration of alkaline phosphatase, especially its bone isoenzyme
Paget’s bone disease
The Paget’s disease typically affects only certain parts of the skeleton. It results from
local uncontrolled bone resorption, associated with excessive and disorganized bone
formation. The structure of produced bone is defective. Numbers of both osteoclasts
and osteoblasts are elevated.
The biochemical findings are dominated by an increased value of alkaline
phosphatase (bone isoenzyme). Estimation of bone resorption markers is also useful.
What happens to calcium and phosphate in chronic kidney disease?
As someone develops chronic kidney disease, the following sequence of events might
occur:
1. The kidneys can no longer convert vitamin D to its active form, so the body can no
longer absorb calcium from food in the gut, which means the level of calcium in the
blood falls.
2. At the same time, because the kidneys are not working as efficiently as normal,
they are unable to excrete excess phosphate into the urine. Thus the level of
phosphate in the blood rises, which can cause intense itching all over the body.
3. The low levels of calcium in the blood cause PTH to be produced in large
quantities. The PTH tries to restore the calcium level in the blood to normal by
increasing the amount of calcium absorbed from food. However, it also takes calcium
out of the bones, which in turn causes weakening of the bones, and renal bone
disease, or, as it is now called, metabolic bone disorder of chronic kidney disease.

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Chapter 1
What is the normal range for plasma Ca?
a) 19–30.4 mg/100ml b) 9–10.4 mg/100ml
c) 90–110 mg/1 d) >50mg/100ml e)
Which one of following statements best describes the metabolic function of
phosphorus?
a) Phosphorus occurs as hydroxyapatite in calcified tissues and as phosolipids, and
has no other roles in the body.
b) Phosphorus occurs as hydroxyapatite in calcified tissues and as phosolipids, and
also plays a role in the buffering of acid or alkali excesses, and the temporary storage
and transfer of energy derived from metabolic fuels.
c) Phosphorus is only involved in calcium homeostasis.
d) Phosphorus is toxic to the body and plays no key role.
e) None of the above.
Calcium is excreted by
(A) Kidney (B) Kidney and intestine
(C) Kidney and (D) Kidney and pancreas
A decrease in the ionized fraction of serum calcium causes
(A) Tetany (B) Rickets
(C) Osteomalacia (D) Osteoporosis
An inherited or acquired renal tubular defect in the reabsorption of phosphate
(Vit D resistant ricket) is characterized with
(A) Normal serum Phosphate
(B) High serum phosphate
(C) A low blood phosphorous with elevated alkaline Phosphate

(D) A high blood phosphorous with decreased alkaline phosphatase

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(3) Magnesium
A) Sources: Widespread in foods and water (except soft water); especially found in
grains, legumes, nuts, seeds, green vegetables

B) Absorption: Occurs in the upper small intestine.

Magnesium is absorbed in the intestines and then transported through the blood to
cells and tissues. Approximately one-third to one-half of dietary magnesium is
absorbed into the body.

C) Body magnesium:

1. Mostly (70%) in the skeleton (bones and teeth).

2. The remaining 30% is present in the other tissues and body fluids mostly
intracellular.

D) Blood magnesium;

1. Plasma magnesium: 2-3 mg/dl.

2. RBCs content of magnesium is 3 times greater than plasma content.

E) Functions:

Magnesium is an active component of several enzyme systems in which thymine

pyrophosphate is a cofactor. Oxidative phosphorylation is greatly reduced in the
absence of magnesium. Mg is also an essential activator for the phosphate-
transferring enzymes myokinase, diphophopyridinenucleotide kinase, and creatine
kinase. It also activates pyruvic acid carboxylase, pyruvic acid oxidase, and the
condensing enzyme for the reactions in the citric acid cycle. It is also a constituent of
bones, teeth, enzyme cofactor, (kinases, etc), The health status of the digestive system
and the kidneys significantly influence magnesium status.

 It enters in the structure of skeleton (bones and teeth).

 It activates many enzymes e.g. kinase enzymes.

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Lipids & Minerals

 It is required for the active transport of other cations (Ca++, Na+, K+) across
the cell membrane.
 It is important for muscle contraction, nerve impulse
transmission and it decreases neuromuscular excitability.

F) Excretion: Mostly (75 %) in feces.

G) Requirements: For adults: 400 mg/day.

Magnesium deficiency

Gastrointestinal disorders that impair absorption such as Crohn's disease can limit the
body's ability to absorb magnesium. These disorders can deplete the body's stores of
magnesium and in extreme cases may result in magnesium deficiency. When a
magnesium-deficient diet is fed to young chicks, it leads to poor growth and
feathering, decreased muscle tone, ataxia, progressive incoordination and convulsions
followed by death. Chronic or excessive vomiting and diarrhea may also result in
magnesium depletion. Deficiency diseases or symptoms is secondary to
malabsorption or diarrhoea, alcoholism. Acute magnesium deficiency results in
vasodilation, with erythemia and hyperaemia appearing a few days on the deficient
diet. Neuromuscular hyperirritability increases with the continuation of the
deficiency, and may be followed eventually by cardiac arrhythmia and generalized
tremours. A common form of magenesium-deficiency tetany in ruminants is called
grass tetany or wheat wheat-pasture poisoning. This condition occurs in ruminants
grazing on rapidly growing young grasses or cereal crops and develops very quickly.
The physiological deficiency of magnesium can be prevented by magnesium
supplementation of a salt or grain mixture and adequate consumption is also very
important. Toxicity disease or symptoms of magnesium deficiency in humans include
depressed deep tendon reflexes and respiration. Sources include leafy green vegetable
(containing chlorophyll).

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(4) Sodium:
A) Sources:
The difference between "sodium" and "salt" can be confusing.
• Sodium is a mineral found in various foods including table salt. (NaCl - sodium
chloride)
• Table salt is 40% sodium (sodium chloride).
• Also combined with other chemicals and added to manufactured foods.
B) Absorption: It occurs in small intestine (ileum). It is nearly completely absorbed.
Sodium is absorbed by sodium pump situated in basal and lateral plasma membrane
of intestinal and renal cells. Na-pump actively transports Na into extracellular fluid.
SODIUM PUMP
• This is also called as Na⁺ ₋ K⁺ ATPase.
• It requires ATP and Mg⁺ ⁺ .
•Na-pump is an enzyme, Na⁺ ₋ K⁺ ₋ ATPase.
• It is a glycoprotein composed of 2 α and 2 β chains.
• Its activity depends on presence of Na⁺ and K⁺ .

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C. Body sodium: It is regulated by aldosterone.

1. 2/3 of sodium is present in tissues and body fluids (sodium is the main
extracellular cation).

2. About 1/3 of sodium is present in skeleton.

D. Plasma sodium: 137-143 mmol/L.

Factors affecting plasma sodium:

1. Aldosterone and the rennin angiotensin system ( Plasm

sodium).

2. Changes in glomerular filtrate and renal blood flow.

3. Atrial natriuretic peptide.

E) Functions:

1. Maintenance of osmotic pressure and volume of plasma and extracellular fluid.

2. Transmission of nerve impulses.

3. Contraction of muscles.

4. Regulation of acid base balance.

5. Sodium acts as substrate for Na+/K+ ATPase enzyme (sodium potassium

pump).

F. Excretion: Mainly (95%) in urine and sweat.

G. Requirements: For adults: 5 g/day.

H. Alterations of plasma sodium:

1. Hypernatremia (excess plasma sodium): It is caused by:

a) Gushing syndrome: due to excessive glucocorticoids.

b) Conn's disease: due to excessive aldosterone secretion.

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c) Diabetes insipidus (4-ADH): due to rapid loss of water.

d) Drugs: as ACTH or cortisone.

2. Hyponatremia (decrease plasma sodium) : It is caused by:

a) Addison's disease: due to deficiency of aldosterone.

b) Renal failure: where renal reabsorption of sodium is

inhibited.

c) Hypotonic dehydration: where loss of water and sodium

(electrolytes) is treated by administration of water only.

d) Diuretics: e.g. thiazides, which block tubular reabsorption of sodium.

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(5) Potassium
A) Sources: Vegetables, fruits and nuts. Potassium is a mineral found in foods It is
also an electrolyte, which conducts electrical impulses throughout the body It is an
essential nutrient because it is not produced naturally by the body
Therefore it is important to consume the right balance of potassium-rich foods and
beverages

B) Absorption: Rapidly occurs in the small intestine.

C) Body potassium:

It is regulated by aldosterone.

1. 2/3 of potassium is present in tissues and body fluids

(potassium is the main intracellular cation).

2. About 1/3 is present in skeleton.

D. Plasma potassium: 3.5-5 mmol/L.

E. Functions:

 Body fluid is composed of water and electrolytes

 Water: dissolves and transport substances, account for blood volume, maintain
body temperature, protect and lubricate tissues
 Electrolytes (Potassium K+, Sodium Na+, Chloride Cl- & Phosphorus HPO42-
), form ions when dissolve in water and are capable of carrying an electrical
current. The electrical charge acts as a ―spark‖ that stimulates nerves and
causes muscles to contract. K+ and HPO42- are dominant in the intracellular
fluid and Na+ and Cl- in the extracellular. The occurrence of these electrolytes
on either side of the cell membrane creates a difference in electrical charge and
this is needed in order for the cell to perform its normal functions.
1. Maintenance of osmotic pressure and volume of intracellular fluid.

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Cells contain a relatively high concentrations of potassium ions but low

concentrations of sodium ions. Most of the sodium ions are in the extracellular fluid
compartment.
The sodium-potassium pump moves two ions in opposite directions across the plasma
membrane. The two sides of the membrane are interdependent The protein carrier
ATP-ase transports both ions. The pump pumps three sodium ions out of the cell for
every two potassium ions pumped into the cell.
The balance between sodium and potassium creates an electrical and chemical
gradient that functions to transport molecules in and out of the cell and transmit nerve
signals that induce muscle contraction and induce functions related to muscles.

Thirst: A desire to drink fluids in response to an increase in the concentration of Na+

in the blood or decrease in blood pressure and volume.
Increased salt concentration (Na+) in the blood. Water moves from the cell into the
ECF.
Reduction in blood volume and blood pressure (vomiting, sweating, blood loss,
diarrhoea and low fluid intake dryness in tissues of the mouth and throat
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2. Transmission of nerve impulses.

Repolarisation: Release of potassium to the exterior of the cell allows the first portion
of the membrane to return to the resting state until next stimulation In the absence of
potassium, this sequence of events will not take place and therefore no nervous
impulse transmission can occur.

3. Contraction of muscles.

The electrical impulse generated by potassium stimulates calcium ions to move

across the cell membrane to the fluid surrounding the cell. This movement of calcium
ions triggers the muscle cells to contract and aids in movement. A low potassium
level inhibits muscle relaxation, causing rigid muscles that lead to tension and
impaired function.
Common symptoms of potassium deficiency include muscle weakness and spasms.
4. Regulation of acid base balance.
5. Substrate for Na+/K+ ATPase.
6. Other functions
Glucose and insulin metabolism
• Potassium, (serum and extent dietary intake levels), has been associated with
incident of diabetes.
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• Lower levels of potassium have been found to be associated with a higher risk of
diabetes through interference on the
functioning of beta cells
• Hypokalemia lead to impaired glucose tolerance by reducing insulin secretion in
response to glucose loads as well as interruption on glucose transportation at the cell
membrane.
Hormone secretion
Renal concentrating ability
Mineral-corticoid action
Body Growth and Development
Activate enzymes
Metabolism of carbohydrates and proteins.

F. Excretion:; Mainly in urine.

G. Requirements: 4 g/day.

H. Alterations of plasma potassium:

1. Hyperkalemia (excess plasma potassium): it is caused by:

a) Addisonvs disease: due to deficiency of aldosterone.

b) Acidosis: (respiratory or metabolic): due to shift of K+ from

intra to extracellular in exchange with H + .

c) Tissue necrosis: e.g. major trauma and burns due to

leakage of tissue contents of potassium.

d) Acute renal failure and advanced chronic renal

failure, associated with oliguria.

e) Uncontrolled diabetes mellitus: the lack of insulin and

associated acidosis prevents K+ from entering cells.

 Acute hyperkalemia: if plasma K+ gets more than 6.5 mmol/L, cardiac

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arrhythmias and even cardiac arrest may result.

2. Hypokalemia: (decreased plasma potassium): it is caused by:

a) Alkalosis: (respiratory or metabolic).

b) Treatment of hyperglycemia: by insulin without giving

potassium because insulin helps K+ to enter cells.

c) Excessive vomiting and diarrhea.

d) Cushing syndrome: due to excessive glucocorticoids.

e) Primary and secondary hyper-aldosteronism.

f) Diuretic therapy.

(6) Chloride
A. Sources: Table salt.

B. Absorption: Occurs in small intestine. C. Plasma chloride; 96-106 mmol/L.

D. Functions:

1. Chloride is the main extracellular anion. Together with

sodium, it maintains the osmotic pressure and volume of plasma and
extracellular fluid.

2. Chloride ions are essential for formation of HC1 in the stomach.

3. Activation of enzymes: Cl~ activates salivary and pancreatic
amylase enzymes.
E. Excretion: Mainly in urine.

F. Requirements: For adults: 5 g/day.

G. Alterations of plasma chloride;

1. Hyperchloremia:
a) Hyperchloremic acidosis:

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Occurs when HCO3- is lost in exchange with chloride as in renal tubular

acidosis and hyperventilation.
b) Glomerulonephritis.
c) Eclampsia (toxicity of pregnancy).
2. Hypochloremia:
a) Hypochloremic alkalosis: decreased plasma chloride due to:
1) Intestinal obstruction  excessive vomiting.
2) This leads to decrease plasma chloride and increase plasma bicarbonate as
compensatory mechanism, causing alkalosis.
b) Addison's disease.
c) Diabetes insipidus.

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(B) Microminerals
(Trace Elements)

(1) Iron
A. Sources;

1. Liver, heart, kidney, spleen and fish.

2. Sugar cane syrup (molasses).

3. Dates and egg yolk.

4. Contrary to popular belief, spinach is a poor source of iron because it is bound

to phytate, which is difficult to absorb.

B. Absorption: Absorption of iron occurs in the duodenum and the proximal part of
the jejunum.

1. Diet contains about 10-20 mg iron/day. Usually 10-20% of this amount is

only absorbed.

2. Mechanism: Mucosal block theory:

a) According to this theory, iron is absorbed in the ferrous state (Fe + + ). Inside

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mucosal cells, it is oxidized to ferric state (Fe + ++) and combines with
apoferritin to form ferritin.

b) Ferritin liberates ferrous ions into the capillaries (plasma) and apoferritin is
regenerated again. The rate of this liberation depends on body needs.

c) The intestinal content of apoferritin is limited and when all apoferritin

molecules become saturated with iron, absorption is blocked.

3. Factors affecting iron absorption: most of dietary iron is

present in the ferric state (Fe+++) as ferric organic compounds.

a) Factors promoting iron absorption:

1) Cooking of food and gastric HC1 facilitates the

liberation of ferric ions (Fe+++) from organic
compounds.

2) Reducing substances: vitamin C and cysteine (-SH) of

dietary protein help the reduction of ferric ions (Fe+++) into the absorbable
ferrous (Fe++) state.

3) Body needs: absorption occurs only if the body is in

need to iron. More iron is absorbed when there is irOn
deficiency or when erythropoiesis is increased.

b) Factors inhibiting iron absorption:

1) High dietary phosphate and phytate: They form

insoluble, non-absorbable organic iron complexes.

2) Steatorrhea: Where fatty acids form non-absorbable

iron soaps.

3) Alkalies and tea.

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4. Recent theory for iron absorption:

a) On the brush borders of mucosal cells, iron binds

with specific carrier protein called metal transporter.

b) It passes inside intestinal mucosal cells.

c) Inside mucosal cells, iron either:

1) leave the intestinal cell and enter the plasma via the transporter known as
ferroportin.

2) Incorporated into ferritin formation i.e. ferritin acts as storage compound and
not as a carrier for iron absorption.

C. Body iron:

1. The total body iron of an adult male is 3-5 grams.

2. It is distributed as follows: RBCs iron (Hemoglobin): 66%, tissue iron (33%)

and plasma iron 1%.

3. RBCs iron: (hemoglobin): see hemoglobin metabolism.

4. Tissue iron: it includes:

a) Available iron forms (29 %): i.e. can be used by tissues when there is body
need,

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II) Ferritin:

i- It is the main storage form of iron.

ii- It is formed of a protein called apoferritin,

which can carry 3500-4000 atoms of iron to
form ferritin.

iii- It is present in iron stores: liver, spleen, bone

marrow and intestine.
II) Hemosedrin:
i- When body contains very high content of iron more than the capacity of apoferritin,
some of iron is found in granules called hemosedrin that deposited in tissues.

ii- These granules are composed of iron, protein, and polysaccharides.

iii- Hemosedrin may be a degraded ferritin.

b) Non-available iron forms (4%): cannot be used even if there is body needs.
All these forms are hemoproteins i.e. contain heme ring.
1) Myoglobin:
i- It is hemoprotein formed of a single heme ring attached to one long polypeptide
chain.
ii- It is present in muscles and heart.

iii- It acts as oxygen reservoir for quick utilization by contracting muscles.

2) Respiratory cytochromes (b, Cl, c, a, a3):

i- These are components of respiratory chain in mitochondria.

ii- They act as electron carriers.
3) Catalase and peroxidase:
i- These are two enzymes that act on the toxic hydrogen peroxide (H2O2)
converting it into H2O.
4) Tryptophan oxygenase (pyrrolase):
i- This enzyme is important for tryptophan metabolism.
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Lipids & Minerals

5) Cytochrome P450:
i- These are a specific group of enzymes that present in liver, lung, kidney, gut,
adrenal cortex, heart, and brain. They are used in xenobiotics metabolism.
5. Plasma iron:
a) Plasma iron: Ranges from 60 - 160 ug/dl.
b) Plasma transferrin:
1) This is a plasma glycoprotein that acts as carrier for
iron. It is synthesized in the liver.
2) Each molecule can carry 2 atoms of iron in ferric state
(Fe3+).
3) Transferrin may carry up to 180-450 ug iron/dl. This
is known as total iron binding capacity of transferrin
(TIBC). As the plasma iron is 60-160 ug/dl, thus only
30% of the TIBC of transferrin is saturated.
4) TIBC is therefore defined as maximum amount of
iron that can be carried by transferrin per
deciliter.
5) Abnormalities of plasma TIBC concentration:

i- In iron deficiency anemia: Plasma iron is decreased. Liver synthesizes more

transferrin with subsequent increase of TIBC.

ii- In liver diseases: Both plasma iron and transferrin synthesis tend to decrease (4
plasma iron and iTIBC).

iii- In iron overload: transferrin synthesis is inhibited. This leads to increased plasma
iron and decreased Total iron binding capacity.

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c) Plasma ferritin:

1) Ferritin is present mainly in iron stores: liver, spleen,

bone marrow and intestine.

2) Very low concentration of ferritin is present in

plasma.

3) Measurement of plasma ferritin gives a good idea about

body iron stores.

i- A low plasma ferritin indicates the presence of depleted iron stores e.g. in iron
deficiency anemia.

ii-A raised plasma ferritin is found in iron overload and also in many patients
with liver disease and cancer.

D. Functions of iron: Iron enters in the structure of the following compounds:

1. Hemoglobin: This carries oxygen.

2. Myoglobin: This stores oxygen.

3. Respiratory enzymes: that use oxygen.

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Lipids & Minerals

4. Cytochrome P45o: This detoxicates drugs and oxygen.

5. Other enzymes: catalase, peroxidase and tryptophan oxygenase.

E. Transport and storage of plasma iron:

1. Absorbed iron enters in the portal blood in ferrous state (Fe++).

2. In the plasma, it is rapidly oxidized to ferric state (Fe+++), A protein containing

copper called ceruloplasmin catalyzes this oxidation.

Fe++ Ceruloplasmin Fe+++

3. Then ferric ions are carried by a transferrin, which is taken mostly by bone
marrow to synthesize hemoglobin.

4. Iron, from iron stores (ferritin) can be released into plasma and carried by
transferrin to be utilized by bone marrow and other tissues.

F. Excretion;

1. Iron excreted in the feces is mainly exogenous i.e. dietary iron that has not
been absorbed.

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Lipids & Minerals

2. In males there is an average loss of endogenous iron of about 1 mg/day. It is

derived from desquamated cells from skin and the intestinal mucosa.

3. In females, there are additional sources of loss, due to

menstruation and pregnancy.
4. Urine contains negligible amount of iron.
G. Requirements;
1. Adults: 10 mg/day.
2. Pregnant and lactating women: 30 mg/day.
H. Alterations of plasma iron;
1. Iron deficiency anemia:
a) Causes:
1) Deficient intake.
2) Impaired absorption: e.g. steatorrhea, abdominal surgery.
3) Excessive loss e.g. menstrual loss, gastrointestinal bleeding due to some
parasites (anchylostoma).
b) Biochemical changes:
1) Plasma iron is decreased.
2) Plasma TIBC is increased.
3) Plasma ferritin is decreased.
4) RBCs show: hypochromic, microcytic cells.
2. Iron overload:

a) Causes:

1) Repeated blood transfusion.

2) Intravenous administration of iron.

3) Hemochromatosis (hemosiderosis, bronze diabetes):

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i- This is a rare hereditary disease characterized by abnormal increase of iron

absorption.

ii- Iron is deposited in the form of hemosedrin in:

 Liver: causing liver cirrhosis.

 Pancreas: causing fibrosis and diabetes mellitus.

 Skin: causing bronze discoloration of skin.

b) Biochemical changes:

1) Plasma iron is increased.

2) Plasma TIBC is decreased.

3) Plasma ferritin is increased.
(2) Copper
A. Sources: The copper content of soil determines the amount in foodstuff. Dairy
products are generally poor source of copper. Whole grain cereals, organ meats, shell
fish, nuts, dried legumes are good sources of copper. Human milk contains 200 – 600
μg/litre. Absorption from breast milk is high because of presence of ligands that
facilitate absorption. Cow’s milk contains 150 μg/litre. Infant formulae show a wide
variation world-wide.

B. Absorption: Mainly occurs in the upper small intestine. the proportion absorbed
depending upon the dietary form and other constituents of diet like calcium, iron, or
zinc which interfere with absorption.

C. Body copper:

1. The adult human body contains about 100-150 mg of copper.

2. 64 mg (50%) are found in muscles and the remaining present in other tissues
including liver and bones.

D. Blood copper:
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Lipids & Minerals

1. In the plasma: 90 ug/dl. It is present in association of 2

proteins:

a) Ceruloplasmin: (90%) A copper binding protein. Each

molecule can bind 6 atoms of copper. It acts as ferroxidase enzyme during
iron metabolism (Fe++  Fe+++).

b) Albumin: (10%) It is loosely bound form of copper. It acts as a carrier for

transport of copper in plasma.

2) In red cells: 100 ug/dl. It is present in association of the

enzyme superoxide dismutase (erythrocuprein), which deals
with the toxic free radical superoxide ion (O2~) generated during aerobic
metabolism.

E. Functions:

1. Copper is essential for:

a) Hemoglobin synthesis.

b) Bone formation.

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c) Maintenance of myelin of the nerves.

2. Copper is essential constituent of several metalo-enzymes:

a) Ceruloplasmin: which oxidizes Fe++ into Fe+ + + in the

plasma.

b) Superoxide dismutase: which eliminates the toxic effect

of superoxide ions (O2-).

 Superoxide dismutase is present in RBCs (erythrocuprein), liver (hepatocuprein)

and brain (cerebrocuprein).

c) Cytochrome oxidase

3. Copper activates many enzymes: e.g. tyrosinase, uricase and dopamine

hydroxylase.

F. Excretion:

1. Mainly with bile, the liver plays a prominent role in copper distribution to organs
and regulates overall system homeostasis. Bile, not urine, for eventual loss in the
stool, is the major excretory route for copper. Normal urine copper loss is 20–50
μg/day, whereas stool copper loss is in the order of 1.0 mg/day.

2. Urinary excretion is minimal due to large molecular weight of Ceruloplasmin.

G. Requirements: Adults: 2 - 3 mg/day.

H. Alterations of plasma copper:

1. Hypercupermia: (excess plasma copper and Ceruloplasmin): Ceruloplasmin is

considered as acute phase protein i.e. its plasma level is increased in infections and
malignancy.

2. Hypocupermia: (decreased plasma copper and ceruloplasmin):

a) Anemia: Hypochromic and microcytic anemia.

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b) Impaired bone mineralization.

c) Wilson's disease (hepatolenticular degeneration):

1) This disease is characterized by accumulation of large

amounts of copper in:

i- Liver causing hepatic cirrhosis.

ii- Lenticular nucleus of the brain causing lenticular degeneration with abnormal
movement.

iii- Cornea: Causing greenish-brown discoloration of the corneal margin, which is

called: Kayser -Fleisher rings,

iv-Kidney causing renal tubular damage which leads to:

 Increased excretion of copper and ceruloplasmin.

This results in low serum copper (hypocupremia)
and ceruloplasmin.

 Increased excretion of amino acids. This results in

aminoaciduria.

2) The cause of the disease is most probably due to either:

i- Excessive copper absorption from intestine,

ii- Inadequate excretion of copper in bile.

Copper deficiency

 Copper deficiency disease is rare except in specific groups such as very low birth
weight infant, in children treated for protein energy malnutrition with a milk based
diet low in copper for a long period, in children with protracted diarrhoea, and
during parenteral feeding.

 Copper deficiency leads to intracellular abnormality of iron metabolism because

of defective iron transport causing inefficient production of heme, and a

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hypochromic anaemia not responding to iron. In pre-term infants copper

deficiency may present as severe osteoporosis with cupping and flaring of the
bone ends, periosteal reaction and sub-metaphyseal fractures. Skin rash similar to
seborrhoeic dermatitis, failure to thrive, psychomotor retardation and
heptosplenomegaly are other signs of copper deficiency.
Two conditions due to abnormalities of copper metabolism have been described.
Wilson’s disease (hepatolenticular degeneration) is an autosomal recessive condition
in which excessive accumulation of copper occurs in tissues. Accumulation in
erythrocytes, liver, brain and kidneys accounts for most of the symptoms. In
erythrocytes it leads to acute haemolytic anaemia. Hepatic insufficiency is followed
by cirrhosis and liver failure. Accumulation of copper in nerve cells causes tremors,
choreo-athetoid movements and eventually dementia. Menke’s steely hair
syndrome is a severe and eventually fatal involvement of the central nervous system
due to disorders of copper metabolism in brain cells.

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Chapter 2

Daily requirement of iron for normal adult male is about

(A) 5 mg (B) 10 mg (C) 15 mg (D) 20 mg
The absorption of iron is increased 2–10 times of normal in
(A) Iron deficiency anemia (B) Pregnancy
(C) Spherocytosis (D) Sickle cell anemia
Molecular iron is
(A) Stored primarily in the spleen
(B) Exreted in the urine as Fe2+
(C) Stored in the body in combination with ferritin
(D) Absorbed in the ferric form
Menke’s disease is due to an abnormality in the metabolism of
(A) Iron (B) Manganese
(C) Magnesium (D) Copper
The cytosolic superoxide dismutase enzyme contains
(A) Cu2+ (B) Cu2+ and Zn2+
(C) Zn2+ (D) Mn2+

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(3) Zinc
The requirement for zinc is 1 mg/day in infancy; 10 mg/day between 1 and 10 years
of age, and 15 mg/day in adults. It is not generally appreciated that as much zinc as
iron is required in the diet. There is no body store for zinc unlike iron.

All the zinc is locked in bone or protein which explains the rapidity of onset of
symptoms on a deficient diet. In this respect zinc resembles essential amino acids.
This similarity as well as the non-specific nature of zinc deficiency signs suggests
that zinc deficiency causes a block in protein and nucleic acid synthesis. The immune
system, the skin and the gastro-intestinal tract are the tissues of the body with the
highest rate of protein synthesis, and they are the main targets for deficiency signs to
appear.

Absorption of zinc occurs by a saturable mechanism that is carrier mediated. A

number of ligands facilitate uptake by the mucosal cells. Zinc attached to transferrin
travels from the mucosal enterocytes to the liver in the portal circulation. In the
systemic circulation approximately two-thirds of plasma zinc is loosely bound to
albumin and the remainder to globulin. In the tissues highest known concentrations of
zinc occur in the eye, bone and hair, and to a lesser extent in muscle and kidney.

The primary route of excretion is by way of the gastro-intestinal tract with

desquamation of mucosal cells.
C. Body zinc;
1. The adult male body contains about 2 g of zinc.

2. About 20 % of total body zinc is present in the skin.

3. The remaining is present in skeleton (bones and teeth),

spermatozoa, prostate, epididymis and pancreas.
D. Plasma zinc: Adults: 70-150 ug/dl.
E. Functions of zinc;

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Zinc is involved in nucleic acid synthesis, protein metabolism, carbohydrate

metabolism, bone metabolism, oxygen transport and protection against free radical
damage. Such a large variety of functions is possible because zinc is a constituent of
several hundred metallo-enzymes. In some of these enzymes zinc is present at the
active site; in others and in some non-enzyme proteins the function of zinc is
structural.

Zinc helps to stabilise the structures of DNA, RNA, and ribosomes. It is involved in
normal chromatin restructuring, and in gene expression.

Zinc also seems to have an important role in the structure and function of membranes.
It also plays an important role in the immune system especially T-cell function.

A meta analysis of 33 prospective intervention studies of zinc supplementation and

its effects on children’s growth in many countries showed that zinc supplementation
alone had a significant effect on linear growth and gain in weight.

Zinc supplementation has been shown to reduce the incidence and duration of acute
and persistent diarrhoea as well as acute respiratory infection in children.

F. Requirements: An adult male: 10-20 mg/day.

G. Excretion: Mainly in feces (mostly unabsorbed dietary zinc).

H. Zinc deficiency
Decrease in growth velocity or total arrest of growth is a consistent and early result of
zinc deficiency in infants, children and adolescents. In acute zinc deficiency states
e.g. acrodermatitis enteropathica there is an abrupt cessation of weight gain and
appearance of skin rash. It presents a few weeks following birth after foetal stores are
exhausted.

Acrodermatitis enteropathica is an autosomal recessively inherited disorder in which

there is a partial block in the intestinal absorption of zinc. It used to be a severe,
progressive and even fatal condition before the benefits of zinc therapy were realised.

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Factor or factors in human milk help to ameliorate the clinical and biochemical
abnormalities. Catch-up growth occurs when zinc supplements
are administered. The skin lesions have a characteristic
distribution, primarily on the extremities and adjacent to body
orifices. Secondary infection of the vesicles is common and
difficult to heal. Frequent bacterial and monilial infections due
to abnormalities of the immune system are common.

Many of the features of zinc deficiency like, for example, growth retardation, poor
wound healing, abnormalities in the immune system, are attributable to disturbance in
nucleic acid metabolism and protein synthesis. Sodium transport across cell
membrane is affected by zinc deficiency which explains the diarrhoea characteristic
of zinc deficiency.

Etiological factors in zinc deficiency. Dietary zinc deficiency is rare and occurs only
in exceptional circumstances in the case of subjects on synthetic diets, or because of
factors in the diet that interfere with bioavailability like high levels of phytate and
fibre together with low levels of animal protein.
(4) Iodine
A. Sources;

1. Iodinized table salt will provide daily body needs.

2. Fish, seafoods, weeds, and vegetables grown near seaboard.

B. Absorption: Occurs mainly from small intestine.

C. Body iodine:
1. The adult male body contains about 25-50 mg iodine.
2. It is present in:
a) Thyroid gland: (50%): as thyroglobulin.
b) Other tissues and body fluids (50%): as T3 and T4.

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D. Plasma iodine:
1. Organic iodine: 4-8 ug/dl.
2. Inorganic iodine: 1-2 ug/dl.
E. Functions;
The only known function of iodine is the formation of thyroid hormones (T3 - T4).
F. Excretion: Mainly (70%) in urine.
G. Requirements:
For adult: 100 - 150 ug/day.
H. Deficiency:
Hypothyroidism (myxodema in adults and cretinism in children).

(5) Selenium
(A) Food Sources
Dietary requirements and the food sources. Human milk contains 15 – 20 μg/litre.
Thus the intake in a young breast fed infant is about 3 μg/kg body weight per day.
The concentration in foods varies with geographical region and soil content. Sea food
(0.5 μg/g), kidney, liver, meat (approximately 0.2 μg/g), and whole grains are good
sources. Vegetables and fruits provide little selenium.
Absorption of selenium depends on the chemical form, the organic form being better
absorbed than the inorganic. Intestinal absorption can be as much as 80 per cent.
Principal route of excretion is by way of the kidney. Highest tissue concentrations are
found in the liver, tooth enamel, and nails.
(B) Selenium function
Selenium has an important role as an essential component of glutathione peroxidase
in which it provides the active site. This enzyme utilizes two molecules of reduced
glutathione to reduce hydrogen peroxide and convert it to two molecules of water. It
also catalyzes the reduction of fatty acid hydro peroxides to hydroxy acids in the
tissues and thus helps to protect the lipids of cell membranes fro peroxidation.
Selenium is thus important for maintaining membrane stability and for controlling

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free radical damage. Glutathione peroxidase is present in a wide variety of tissues and
accounts for 90 per cent of the selenium in erythrocytes.
Selenium is an antioxidant. It is an essential component of the enzyme glutathione
peroxidase (GSH-Px) which catalyzes the reaction:
2 GSH + H2O2 GSH-Px GSSG + 2H2O
(C) This reaction acts as protective mechanism against the oxidative damage of
hydrogen peroxide (H2O2) and fatty acid hydroperoxide by destroying them:
1. In RBCs, it protects hemoglobin and red cell membranes.
2. In liver, it is important for detoxifying lipid hydroperoxides.
3. In lens of the eye, it prevents its oxidative damage.
(D) Deficiency of selenium (GSH-Px): It causes:
1. Hemolytic anemia.
2. Liver cirrhosis.
3. Cataract.
(E) Selenium and Cancer Prevention
• Epidemiologic evidence indicates low intakes of Se are associated with higher risk
of prostate cancer
• Prospective study of Se supplementation demonstrated 42% reduction in cancer
incidence.
• Small sample size and other confounding factors have diminished enthusiasm for
the results of these studies.

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(6) Manganese
A. Manganese is essential for:

1. Normal bone structure.

2. Reproduction (spermatogenesis and ovulation).

3. Normal function of the central nervous system.

B. Manganese is a component of;

1. Pyruvate carboxylase enzyme.

2. Superoxide dismutase enzyme.

C. Manganese activates: the arginase enzyme.

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(7) Cobalt
(A) Absorption and Excretion

-shared with Fe

-absorption is increased in pts with deficient Fe intake, portal cirrhosis with Fe

overload, and hemochromatosis.

-excretion is mainly thru the urine small amts in feces, hair, sweat

(B) Functions:

1. Cobalt is a component of vitamin Bi2, which is necessary for normal blood cell
formation. Cobalt gives vitamin B12 its red color.

2. Enzymes requiring vitamin B12 for their activities are:

a) Methylmalonyl CoA mutase.

b) Methyltetrahydrofolate oxidoreductase.

c) Homocysteine methyltransferase.

d) Ribonucleotide reductase.

B. Deficiency of cobalt lead to decrease vitamin Bt2 causes pernicious anemia.

(8) Chromium
 It acts only together with insulin to promote glucose utilization.

 Its deficiency leads to impairment of glucose utilization by tissues.

Absorption and Excretion of Chromium

 10-25% absorption in its trivalent form

 Amount absorbed remains constant at dietary intakes >40g (micrograms) at

which point excretion in urine is proportional to intake

 Increased intake of simple sugar, strenuous exercise, or physical trauma also

increase urinary excretion

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 both chromium and Fe are carried by Tf, however albumin can also assume.

Food Sources
 Cereals, meats, poultry, fish, beer
Deficiency
 Altered CHO metabolism, impaired glucose tolerance, glycosuria, fasting
hyperglycemia, increased insulin levels and decreased insulin binding.
 Impaired growth, peripheral neuropathy, negative nitrogen balance.
 Increased chromium losses in stress.
 Hyperglycemia and wt loss reverse with IV supplementation in TPN.
Toxicity
 Chronic renal failure

(9) Molybedenum
 It is a component of oxidase enzymes e.g. xanthine oxidase.

(10) Flouride
 It increases the hardness of bones and teeth.
 Its deficiency causes dental carries and osteoporosis.
 It is supplied in drinking water to support bones and teeth.
 Excess flouride leads to flourosis: mottling and discoloration of the enamel of
teeth and changes in bones.

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(C) WATER METABOLISM

Introduction
Water is the major constituent of the human body. The latter cannot produce enough
water by metabolism or obtain enough water by food ingestion to fulfil its needs. As
a consequence, we need to pay attention to what we drink throughout the day to
ensure that we are meeting our daily water needs, as not doing so may have negative
health effects. Water is the main constituent of cells, tissues and organs and is vital
for life. Despite its well-established importance, water is often forgotten in dietary
recommendations, and the importance of adequate hydration is not mentioned. As a
consequence, health professionals and nutritionists are sometimes confused and
question the necessity of drinking water regularly: how much should we drink, and
how to know whether patients are well hydrated or not. The purpose of this paper is
to review the main functions of water and the mechanisms of daily water balance
regulation, which constitute a clear evidence of how much water we really need.
Water as a vital nutrient: a multifunctional constituent of the human body Water as a
building material Water, present in each cell of our body and in the various tissues
and compartments, acts first as a building material. This primary function leads to
nutritional recommendations, as water needs are higher during the growth period of
the body.
Water as a solvent, a reaction medium, a reactant and a reaction product
Water has unique properties: it is an excellent solvent for ionic compounds and for
solutes such as glucose and amino acids. It is a highly interactive molecule and acts
by weakening electrostatic forces and hydrogen bonding between other polar
molecules. It has a high dielectric constant and it forms oriented solvent shells around
ions, thus enabling them to move freely. Water as a macronutrient is involved in all
hydrolytic reactions, for instance, in the hydrolysis of other macronutrients (proteins,
carbohydrates, lipids and so on). Water is also produced by the oxidative metabolism
of hydrogen-containing substrates in the body. Theoretically, for 1 g of glucose,
palmitic acid and protein (albumin), 0.6, 1.12 and 0.37 ml water, respectively, is
endogenously produced, or for 100 kcal of energy, 15, 13 and 9 ml water is produced.
Water as a carrier Water is essential for cellular homeostasis because it transports
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nutrients to cells and removes wastes from cells. It is the medium in which all
transport systems function, allowing exchanges between cells, interstitial fluid and
capillaries. Water maintains the vascular volume and allows blood circulation, which
is essential for the function of all organs and tissues of the body. Thus, the
cardiovascular and respiratory systems, the digestive tract, the reproductive system,
the kidney and liver, the brain and the peripheral nervous system, all depend on
adequate hydration to function effectively. Severe dehydration therefore affects the
function of many systems and is a life-threatening condition. Water and
thermoregulation Water has a large heat capacity, which contributes to limiting
changes in body temperature in a warm or cold environment. Water has a large
capacity for vaporization of heat, which allows a loss of heat from the body even
when ambient temperature is higher than body temperature. When sweating is
elicited, evaporation of water from the skin surface is a very efficient way to lose
heat. Water as a lubricant and shock absorber Water, in combination with viscous
molecules, forms lubricating fluids for joints; for saliva, gastric and intestinal mucus
secretion in the digestive tract; for mucus in airways secretion in the respiratory
system and for mucus secretion in the genito-urinary tract. By maintaining the
cellular shape, water also acts as a shock absorber during walking or running. This
function is important for the brain and spinal cord, and is particularly important for
the fetus, who is protected by a water cushion. Distribution of body water Water is
the main constituent of our body, as about 60% of our body weight is made of water.
This water content varies with body composition (lean and fat mass). In infants and
children, water as a percentage of body weight is higher than in adults. This is mainly
due to higher water content in the extracellular compartment, whereas the water
content in the intracellular compartment is lower in infants than in older children and
adults. Body composition changes rapidly during the first year of life, with a decrease
in the water content of the fat free mass and an increase in the content of protein and
minerals. In adults, about two-thirds of total water is in the intracellular space,
whereas one-third is extracellular water. A 70-kg human has about 42 l of total body
water, of which 28 l is intracellular water and 14 l is extracellular fluid (ECF). Of the
latter, 3 l is in blood plasma, 1 l is the transcellular fluid (cerebrospinal fluid, ocular,
pleural, peritoneal and synovial fluids) and 10 l is the interstitial fluid, including

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lymph, which provides an aqueous medium surrounding cells. The constancy of the
amount and composition of ECF is a necessity for the function of cells. This
constancy is due to the homeostatic mechanisms that monitor and regulate its
composition, osmotic pressure, pH and temperature. These mechanisms rely on the
function of the main systems of the body, such as the circulatory, respiratory, renal
and alimentary systems. The monitoring and regulation of these systems are
coordinated by the nervous and endocrine systems. The composition of the
intracellular fluid is maintained by solute movement across the cell membrane by
passive or active transports. Water balance: water inputs and outputs. Under usual
conditions of moderate ambient temperature (18–20 1C) and with a moderate activity
level, body water remains relatively constant. This implies a precise regulation of
water balance: over a 24-h period, intake and loss of water must be equal. It has been
estimated that water balance is regulated within 0.2% of body weight over a 24-h
period. Water inputs Water inputs are composed of three major sources the water we
drink, the water we eat and the water we produce. The water we drink is essentially
composed of water and other liquids with a high water content (85 to 490%). The
water we eat comes from various foods with a wide range of water content (40 to
480%). The water we produce results from the oxidation of macronutrients
(endogenous or metabolic water). It is normally assumed that the contribution of food
to total water intake is 20–30%, whereas 70–80% is provided by beverages. This
relationship is not fixed and depends on the type of beverages and on the choice of
foods. For an individual at rest under temperate conditions, the volume that might be
drunk in a day is on an average 1.5 l. This has to be adapted according to age, gender,
climate and physical activity. The water content of food can vary within a wide
range, and consequently the amount of water contributed by foods can vary between
500 ml and 1 l a day. Endogenous or metabolic water represents about 250–350 ml a
day in sedentary people. The adequate total water intakes for sedentary adults are on
an average between 2 and 2.5 l per day (women and men, respectively). In
conclusion, the total water inputs for sedentary adults are on an average between 2
and 3 l. Water outputs. The main routes of water loss from the body are kidneys, skin
and the respiratory tract and, at a very low level, the digestive system. Over a 24-h
period, a sedentary adult produces 1–2 l of urine. Water is lost by evaporation

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through the skin; this is called insensible perspiration because it is an invisible water
loss and it represents about 450 ml of water per day in a temperate environment.
Water is also lost by evaporation through the respiratory tract (250–350 ml per day).
Finally, a sedentary adult loses about 200 ml of water a day through faeces. On an
average, a sedentary adult loses 2–3 l of water per day. These water losses through
the skin and lungs depend on the climate, air temperature and relative humidity.
When the internal body temperature rises, the only mechanism for increasing heat
losses is the activation of sweat glands. Evaporation of water by way of sweat on the
skin surface is a very efficient mechanism for removing heat from the body: 2.2 kJ is
lost by the evaporation of 1 g of water. When exercising in a hot environment, the
sweating rate can reach as much as 1–2 l of water loss per hour. This can lead to
dehydration and hyperosmolarity of ECF. It is important to note that sweat is always
hypotonic when compared with plasma or ECF. Sweat contains 20–50mmol/l of Naþ
, whereas the extracellular Naþ concentration is 150mmol/l. Intense sweating
therefore leads to greater water than electrolyte losses. The consequence is an
increased extracellular osmolarity that draws water from cells into the ECF. Thus, the
loss of water through sweating concerns both intracellular fluid and ECF, a situation
that characterizes hypertonic dehydration. The need to drink hypotonic drinks during
endurance exercise is well established. A person losing 4 l of sweat with no fluid
replacement loses about 10% of body water, but only 4% of extracellular sodium.
This indicates that during exercise, fluid replacement is more important than salt
replacement. Dehydration and hyperosmolarity of ECF can affect consciousness and
are involved in the occurrence of eat stroke when internal temperature rises above
critical thresholds. The latter can occur when exercising in a warm and humid
environment.

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Chapter 3

Metallic constituent of “Glucose tolerance factor” is

(A) Sulphur (B) Cobalt (C) Chromium (D) Selenium
Intestinal absorption of chromium is shared with
(A) Mn (B) Mg (C) Ca (D) Zn
Serum level of chromium in healthy adult is about
(A) 2-5 µg/100 ml (B) 6-20 µg/100 ml
(C) 30-60 µg/100 ml (D) 50-100 µg/100 ml
Chromium is potentiator of
(A) Insulin (B) Glucagon
(C) Thyroxine (D) Parathrom
Recommended daily dietary allowance of selenium for adult human in µg is
(A) 20 (B) 40 (C) 50 (D) 70
Sulphur is made available to the body by the amino acids:
(A) Cystine and methionine (B) Taurine and alanine
(C) Proline and hydroxyproline (D) Arginine and lysine
Iodine is stored in
(A) Thyroid gland as thyroglobulin (B) Liver
(C) Intestine (D) Skin
Fluorosis occurs due to
(A) Drinking water containing less than 0.2 ppm of fluorine
(B) Drinking water containing high calcium
(C) Drinking water containing greater than 1.2 ppm of fluorine
(D) Drinking water containing heavy metals

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Lipids
 The lipids are a large and diverse group of naturally occurring organic compounds
that are related by their solubility in nonpolar organic solvents (e.g. ether,
chloroform, acetone & benzene) and general insolubility in water.
 Lipids contain carbon, hydrogen and oxygen but have far less oxygen
proportionally than carbohydrates. Lipids are an important part of living cells.
Together with carbohydrates and proteins, lipids are the main constituents of plant
and animal cells.
There are different functions for lipids in our bodies:
 Structuring cell membranes. The cell membrane constitutes a barrier for the cell
and controls the flow of material in and out of the cell.
 Energy storage. Triglycerides are an efficient form of energy storage that can be
mobilized when fuel is needed.
 Transmission of information in cells (signal transduction). Lipid hormones, like
steroids and eicosanoids, also mediate communication between cells.
 Cellular metabolism. The fat-soluble vitamins A, D, E, and K are required for
metabolism, usually as coenzymes.
Classification of lipids:
1- Simple lipids:
Simple lipids are esters of fatty acids with certain alcolhols. They classified according
to the the nature of alcohol into the following:
c) Fats and Oils:
 Fats: glycerol esters, solid at room temperature, fatty acids are saturated.
 Oil: glycerol esters, liquid at room temperature, fatty acids are unsaturated.
Fatty Acids:
The carboxylic acid products found in the saponifiable lipids are referred to as fatty
acids. The fatty acids are long, unbranched monocarboxylic acids containing 10 to 22

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carbon atoms. The Fatty acids can be classified into families based on chain length
and on the number of C=C double bonds present. Saturated fatty acids contain no
C=C double bonds. (Saturated = bonded to the maximum number of hydrogens;
Unsaturated fatty acids contain C=C double bonds.

Common Saturated and Unsaturated Fatty Acids

SATURATED FATTY ACIDS

Common IUPAC Name MP RCOOH Condensed

o
Name C Formula Formula

Capric Decanoic 32 C9H19COOH CH3(CH2)8COOH

Lauric Dodecanoic 44 C11H23COOH CH3(CH2)10COOH

Myristic Tetradecanoic 54 C13H27COOH CH3(CH2)12COOH

Palmitic Hexadecanoic 63 C15H31COOH CH3(CH2)14COOH

Stearic Octadecanoic 70 C17H35COOH CH3(CH2)16COOH

Arachidic Eicosanoic 77 C19H39COOH CH3(CH2)18COOH

Common Unsaturated Fatty Acids:

Common I.U.P.A.C MP RCOOH # of Double Bond
o
Names Name C Formula Double Position
Bonds

Palmitoleic cis-9-Hexadecenoic 0 C15H29COOH 1 9

Oleic cis-9-Octadecnoic 16 C17H33COOH 1 9

Linoleic cis,cis-9,12- 5 C17H33COOH 2 9, 12

Octadecadienoic

Linolenic All cis-9,12,15- -11 C17H31COOH 3 9, 12, 15

Octadecatrienoic

Arachidonic All cis-5,8,11,14- -50 C19H31COOH 4 5, 8, 11, 14

Octadecatrienoic

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Condensed Formulas

Palmitoleic CH3(CH2)5CH=CH(CH2)7COOH

Oleic CH3(CH2)7CH=CH(CH2)7COOH

Linoleic CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH

Linolenic CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH

Arachidonic
CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH

d) Waxes:

 Waxes are mixtures comprising chiefly esters of long chain monohydroxy

alcohols and long chain fatty acids. [Paraffin wax is a mixture of solid hydrocarbons
(normally straight-chain).] Waxes differ from fats in that fats contain chiefly esters of
glycerol. Waxes are generally harder and less greasy than fats, but like fats they are
less dense than water and are soluble in alcohol and ether but not in water.
 Due to their high molecular weights, waxes are generally solids at room
temperature. Waxes are found naturally as coating on fruits, leaves, insect
exoskeleton (water retaining). Birds have glands producing wax for feathers (water
repelling).

1- Compound Lipids:

Complex lipids are bonded to other types of

molecules. This group includes the
following important members:

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Phospholipids: Most phospholipids contain a diglyceride, a phosphate group, and a

simple organic molecule. A phospholipid molecule consists of a hydrophilic polar
head group and a hydrophobic tail. The polar head group contains one or more
phosphate groups. The hydrophobic tail is made up of two fatty acyl chains. They
are a major component of all cell membranes as they can form lipid bilayers.

Phospholipids are the principal components of the myelin sheaths of neurons.

Examples of phospholipids include lecithin, cephalins, phosphoinositides (in the
brain), and cardiolipin (in the heart).

a) Glycolipids: are lipids with a carbohydrate attached. Their role is to provide

energy and also serve as markers for cellular recognition. Glycolipids include the
cerebrosides, the sulfatides, and the gangliosides. The cerebrosides are characterized
by a single monosaccharide head group. Sulfatides are a sulfate group containing
derivative of the cerebroside galactocerebroside. Gangliosides are glycolipids
possessing oligosaccharide groups, including one or more molecules of N-
acetylneuroaminic acid (sialic acid).
b) Sulfolipids: are classes of lipids which possess a sulfur-containing functional
group. One of the most common consituents of sulfolipids is sulfoquinovose, which
is acylated to form sulfoquinovosyl diacylglycerols. In plants, sulfolipids are
important intermediates in the sulfur cycle.
c) Lipoproteins: lipoprotein is a biochemical assembly that contains both proteins
and lipids whose function is to transport water-insoluble lipids in the water-based
bloodstream. The lipids or their derivatives may be covalently or non-covalently
bound to the proteins.
The function of lipoprotein particles is to transport lipids (fats) and cholesterol
around the body in the blood.

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There are 4 major classes of plasma lipoproteins: VLDL ―Very Low Density
Lipoprotein‖, LDL ―very Low Density Lipoprotein‖, HDL ―High Density
Lipoprotein‖
2- Derived Lipids: lipids are obtained on hydrolysis of simple and complex lipids.
These lipids contain glycerol and other alcohols. This class of lipids includes steroid
hormones, ketone bodies, hydrocarbons, fatty acids, fatty alcohols, mono and
diglycerides, terpenes and carotenoids. These are sometimes present as waste
products of metabolism.

Miscellaneous lipids
These include compounds, which contain characteristics of lipids. They include
squalene, terpenes, hydrocarbons, carotenoids, etc.
Functions in Biosystem:
 Phospholipids are the constituents of cell membrane and regulate membrane
permeability.
 Phospholipids are also used as detergents to emulsify fat for transport within the
body.
 They act as cellular metabolic regulators.
 They protect internal organs, serve as insulating materials and give shape and
smoothness to the body.
 They serve as a source of fat soluble vitamins.

 Essential fatty acids are useful for transport of cholesterol, formation of lipoproteins,
etc.

 Triacyl glycerols are the concentrated fuel reserves of the body.

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 Phospholipids in mitochondria are responsible for confirmation of electron transport

chain components.

 Phospholipids help in removal of cholesterol from the body by participating in

reverse cholesterol transport.

 Cholesterol is a constituent of membrane structure and it synthesizes bile acids,

hormones and vitamin D. It is the principal sterol of higher animals, abundant in nerve
tissues and gallstones.

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General Tests for Lipids

1) Grease Spot Test:
 Grease Spot Test is general test for all lipid molecules, where all lipids leave
translucent spots (grease spots) on unglazed brown paper bags.
This test also, indicates the solubility of lipids in organic solvents not in water.

2) Cupper acetate test:

 This test differentiates between the saturated and unsaturated fatty acids.

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3) Iodine Test:

 This test detects the degree of saturation of fats and fatty acids.
 As unsaturated fatty acids contain double bonds that have the characteristic
property of adding the iodine or bromine.
 The degree of saturation of a fatty acid or fat is determined by amount of iodine or
bromine absorbed by the fatty acid or fat.

4) Detection of Rancidity in neutral fats and Oils:

 Rancidity leads to the production of free fatty acids by the action of either
bacteria or exposure to atmosphere and sunlight.

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Special Experiments for individual Lipids

Tests for Glycerin: Glycerol or glycerin is tri-hydroxy alcohol
Oxidation Test:
Glycerin ―glycerol‖ may be oxidized into CO2 and H2O.

Dunstan`s Test:

Tests for Cholesterol: It is Specific for cholesterol only.

Lieberman-Burchard Test:
 The Lieberman-Burchard or acetic anhydride test is used for the detection of
cholesterol. The formation of a green or green-blue color after a few minutes is
positive.
 This color begins as a purplish, pink color and progresses through to a light
green then very dark green color. The color is due to the hydroxyl group (-OH) of

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cholesterol reacting with the reagents and increasing the conjugation of the un-
saturation in the adjacent fused ring.

Salkowski`s Test:
Salkowski's test is a test for cholesterol; when concentrated sulfuric acid is added to a
chloroform solution of cholesterol, the chloroform layer shows a red to blue color and
the acid layer shows a green fluorescence.

3) Microscopic Appearance of crystals:

- Put a drop of cholesterol solution on a glass slide and allow it to dry.
- Examine the crystals under microscope.
Cholesterol crystals are flat, rectangular plates with notched corners and are colorless.
They are found in lipiduria or with other forms of urinary fat.

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Guide for identification of unknown Lipid:

Physical properties:
1- Color:
2- Shape:
3- Solubility:
Chemical properties:

No. Experiment Observation Result

1- Grease spot test
2- Cupper acetate test
3- Iodine Test
4- Detection of Rancidity in
neutral fats and Oils
5- Lieberman-Burchard Test
6- Salkowski`s Test
7- Microscopic Appearance of
crystals

So, the unknown Lipid is......................

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Rancidity Test For Lipids

Rancidity is a process which is accompanied by the formation of unpleasant
odor, taste, as a result of the action of moisture, air (O 2) and enzymes. There are
two types of rancidity Hydrolytic rancidity (or lipolytic rancidity) and Oxidative
rancidity.

Test:

i. Dissolve 1 ml of oil in about 2 ml of petroleum ether, ii. Add about 5 ml of

alcohol, and add 2 drops of ph.ph.
iii. Titrate the solution with (0.1 N) NaOH, till faint pink color.
Rancid oil takes 0.4 – 0.5 ml, while unranked oil takes 0.2 ml of alkali.

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Determination of acid value

The acid value IA is the number that expresses, in milligrams the quantity of
potassium hydroxide required to neutralize the free acids present in 1 g of the
substance.
.

gives an indication about edibility of the lipid.

Test:
i. Dissolve 1 g oil in 5 ml of neutralized alcohol on boiling water bath for 5 minutes.
ii. Add 2 drops of ph.ph, and then titrate against (0.1 N) KOH till pink color.

Calculations:
Acid Value" IA" = (5.61 × volume of titration) / weight of sample

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Determination of saponification value

saponifcation value is the number of mg of potassium hydroxide required to
neutralize the free acids and to saponify the esters in 1 g of the substance.
ation value is inversely proportional to the mean molecular weight of
fatty acids (or chain length). S.V. of butter fat and vegetable fats = 220 – 250 ,while
S.V. of fixed oils (vegetable oils) = 195
Test:
i. Weigh 2 g of oil in a clean flask, and boiled it with (0.5N) alcoholic KOH for 1
hour.
ii. At the end of time, the solution is cooled, and adds 2 drops of ph.ph.
iii. Then titrate the solution against (0.5N) HCL till end point and take the volume
"VT."
iv. A blank experiment is also done and takes the volume "VB."
Calculations:
Saponification value = [(VB - VT) × 28.05] / weight of sample
Notes:
The ester value IE is the number that expresses in milligrams the quantity of
potassium hydroxide required to saponify the esters present in 1 g of the substance. It
is calculated from the saponification value IS and the acid value IA:
IE = IS - IA
Saponification equivalent: It is the number of g of lipid saponified by 56.1 g KOH.

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Determination of Total Cholesterol

* Introduction:
- Cholesterol is a steroid with secondary hydroxyl group in the C3 position, and
found in blood, liver, bile and brain tissue.
- Cholesterol serves as a precursor to bile acids, steroids and vitamin D.
-Cholesterol is synthesized in many types of tissue but particularly in liver and
intestinal wall. Approximately, 75 % of cholesterol is newly synthesized and a
25% originates from dietary intake ( egg yolk , brain and liver )

* Principle:
- Tissue homogenate is added to an ethanol ether mixture, which participate proteins
and extracts the cholesterol. The supernatant fluid obtained on centrifuging is
evaporated; the cholesterol is taken up in chloroform then determined
calorimetrically by the Liebermann-Burchard reaction.
* Reagents:
1- Ethanol-ether mixture.
2- Acetic anhydride-sulphuric acid mixture.
3- Chloroform.
4- Standard solution of cholesterol.
* Procedures:
1- Place 10 ml ethanol-ether mixture on a 200 µl of serum sample in a test tube.
2- Transfer the mixture into a centrifuge tube, cork the tube tightly and
shake vigorously for about 1 minute.

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3- Allow the tube to lie horizontally so that the precipitate is distributed along
the tube. Stand for 30 minutes.
4- Centrifuge for a few minutes to get a firm deposit and decant the supernatant
fluid into a test tube.
5- Evaporate to dryness in a water bath.
6- Dissolve the residue, after evaporation, in 5 ml chloroform.
7- Prepare three test tubes: Test, Standard and blank (where the test one containing
the residue).
Contents Test tube Standard tube Blank tube

Chloroform 5 ml 5 ml
Standard 5 ml
Acetic anhydride- 2 ml 2 ml 2 ml

Sulphuric acid
mixture.

8- Mix and stand in dark at 25 c° for 15 minutes.

9- Read the absorbance against chloroform blank at 680 nm.
* Calculation:
mg Cholesterol \ 100 ml blood =
(Absorbance of test \ absorbance of standard) × 0.4 × (100/0.2)

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Determination of total lipids

* Introduction:

- Lipids are important not only for its high energy but because it contains the
fat soluble vitamins A ,D ,E and K and certain essential fatty acids and linoleic acid.
- Lipids are also necessary for nerve sheaths, cholesteolin the bile and to support
and protect certain organs in the body, e.g the kidneys and eyes.
* Principle:
- Total lipids were determined in the liver digests according to the method described
by Knight et al., (1972).
- This method is based on the formation of pink colored complex with
phosphvaniline reagent in acidic medium. The intensity of the color is proportional to
the amount of lipid. The resultant pink color solution was read
spectrophotometrically at 520 nm.
* Reagents:
1- Ethanol- ether mixture.
2- Concentrated sulphuric acid.
3- Phosphovanilline reagent.
4- Cholesterol standard solution
* Procedures:
1- Place 2 ml of ethanol-ether mixture + 200 µl of serum in a test tube.
2- The lipid extract was placed in a test tube and evaporated at 70-80 c° until
dryness.
3- For the pellet 5 ml of conc.H2SO4 were added and heated in a boiling water bath
for 20 minutes with periodical shaking to produce the lipid digest.
4- Prepare three clean test tubes: the test, standard and blank.

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Contents Test tube Standard tube Blank tube

Lipid digest 0.1 ml

Standard solution 0.1 ml

Conc.H2SO4 0.1 ml
Phospho vanilin reagent 3 ml 3 ml 3 ml
5- Left the three tubes in dark for 45 minutes, then read the absorbance against
the blank at 520 nm.
*Calculation:
Total lipid = (Absorbance of Test / Absorbance of Standard) × Concentration of
Standard × (100÷ 0.2) = mg \dl.

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Estimation of Fat in milk

Principle:
 The nature of any fat to be surrounded by protein forming fat globules.

 For estimation of fat content in milk, de-proteinzation of milk, extraction of fat

from protein free filtrate, and then calculate the weigh of fat in milk sample.

 HCL is added to milk and the solution is boiled to denturate the protein
surrounding the fat, then the fat is extracted by ether, the ethereal layer is removed
and ether is evaporated and the fat is weighed.

Procedures:
1- Place 10 ml of milk + 10 ml conc. HCL, boil in a flask with a reflux condenser, for
30 min., till the color becomes dark brown.

2- Cool the solution rapidly under tap water.

3- Transfer the liquid in a cylinder and complete to 50 ml with ether.

4- Shake the liquid for 2 min. to extract fat.

5- Weigh a clean and dry flask "X1".

6- Separate the ethereal layer to the weighed flask using separating funnel.

7- Evaporate the ether layer on a hot plate.

8- Weigh the flask containing fat "X2".

Calculations:
Weight of fat = X2 - X1 = X g
% fat = X / 10.38 × 100 g fat / 100 ml milk

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 Lipids & Minerals

CALCIUM
You have more calcium in your body than any other mineral. Calcium represents
1.5% of total body weight. The body stores more than 99 percent of its calcium in the
bones and teeth to help make and keep them strong. The rest is throughout the body
in blood, muscle and the fluid between cells.
Food sources: Foods rich in calcium include diary products such as milk, cheese
and yogurt, and leafy, green vegetables. The exact amount of calcium you need
depends on your age and other factors. Growing children and teenagers need more
calcium than young adults. Older women need plenty of calcium to prevent
osteoporosis. People who do not eat enough high-calcium foods should take a
calcium supplement.
Functions: Calcium has many important functions Calcium is required for muscle
contraction, blood vessel expansion and contraction, secretion of hormones and
enzymes, and transmitting impulses throughout the nervous system, helps in iron
absorption, blood clotting cascade, activating many enzymes as lipase.
Occurrence & Storage:
The body strives to maintain constant concentrations of calcium in blood, muscle,
and intercellular fluids (1%) of total body calcium to support these functions.
The remaining 99% of the body's calcium supply is stored in the bones and teeth
where it supports their structure. Bone itself undergoes continuous remodeling, with
constant resorption and deposition of calcium into new bone. The balance between
bone resorption and deposition changes with age.
Bone formation exceeds resorption in growing children, whereas in early and middle
adulthood both processes are relatively equal.
In aging adults, particularly among postmenopausal women, bone breakdown
exceeds formation, resulting in bone loss that increases the risk of osteoporosis over
time.

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The percentage of calcium absorbed depends on the total amount of elemental

calcium consumed at one time; as the amount increases, the percentage absorption
decreases. Absorption is highest in doses ≤500 mg.
Side effects of calcium supplement: some individuals who take calcium supplements
might experience gas, bloating, constipation, or a combination of these symptoms.
Such symptoms can often be resolved by spreading out the calcium dose throughout
the day, taking the supplement with meals, or changing the brand of supplement used.
Not all calcium consumed is actually absorbed in the gut. Among the factors that
affect its absorption are the following:
1- Amount consumed: the efficiency of absorption decreases as the amount of

calcium consumed at a meal increases.

2- Age: net calcium absorption is as high as 60% in infants and young children, who
need substantial amounts of the mineral to build bone. Absorption decreases to 15%-
20% in adulthood and continues to decrease as people age; this explains the higher
recommended calcium intakes for age's ≥51 years
3- Vitamin D intake: this nutrient, obtained from food and produced by skin when

exposed to sunlight of sufficient intensity, improves calcium absorption

4- Other components in food: phytic acid and oxalic acid, found naturally in some
plants, bind to calcium and can inhibit its absorption. Foods with high levels of oxalic
acid include spinach, collard greens, sweet potatoes, rhubarb, and beans. Among the
foods high in phytic acid are fiber-containing whole-grain products and wheat bran,
beans, seeds, nuts, and soy isolates. Cellulose and hemicellulose's plants decrease
calcium absorption
Some absorbed calcium is eliminated from the body in urine, feces, and sweat.
This amount is affected by such factors as the following:
1- Sodium, potassium, and protein intakes: high intakes of sodium and protein

increase calcium excretion. Adding more potassium to a high-sodium diet might help
decrease calcium excretion, particularly in postmenopausal women.

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2- Caffeine intake: this stimulant in coffee and tea can modestly increase calcium
excretion and reduce absorption.
3- Alcohol intake: alcohol intake can affect calcium status by reducing its absorption
and by inhibiting enzymes in the liver that help convert vitamin D to its active form.
4- Phosphorus intake: Several observational studies suggest that consumption of
carbonated soft drinks with high levels of phosphate is associated with reduced bone
mass and increased fracture risk. Because the body try to keep the Ca : Ph ratio in
blood is 1:1 and so in case of high phosphorous intake the body try to keep the
proper ratio by bone resorption .
5- Fruit and vegetable intakes: these foods, when metabolized, shift the acid/base
balance of the body towards the alkaline by producing bicarbonate, which reduces
calcium loss.
6- Unabsorbed fats: they interfere with calcium absorption by forming a fatty acid–
calcium soap complex, which is subsequently excreted.
Calcium Deficiency:
Hypocalcemia: results primarily from medical problems or treatments, including
renal failure, surgical removal of the stomach, and use of certain medications (such as
diuretics).
Symptoms of hypocalcemia: include numbness and tingling in the fingers, muscle
cramps, convulsions, lethargy, poor appetite, and abnormal heart rhythms. If left
untreated, calcium deficiency leads to death. A diet deficient in calcium may
increase the risk of rickets, hypertension, osteoporosis, and scurvy.
Health Risks from Excessive Calcium
Hypercalcemia: Excessively high levels of calcium in the blood impair kidney
function, and lead to reduced absorption of other essential minerals, such as iron,
zinc, magnesium, and phosphorus. However, hypercalcemia rarely results from
dietary or supplemental calcium intake and is most commonly associated with

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hyperparathyroidism, advanced cases of cancer or excessive intakes of vitamin D

from supplements at doses of 50,000 IU/day or higher.
Normal value: Normal values range from 8.5 to 10.2 mg/dL.

1- Estimation of Calcium
1- Prepare 3 tubes as following:

2- Mix well and incubate for 1 minute at room temperature

3- Read absorbance at 612 nm
Calculation
Calcium concentration= (Atest/Ast) *conc of st.
Conc of st. =

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PHOSPHOROUS
Next to calcium, phosphorus is the most abundant mineral in the body. Makes up
about 1 percent of our total body weight... About 85% of phosphorus in the body can
be found in bones and teeth (This form of phosphorus, is termed inorganic
phosphorus.), and roughly 10% circulates in the bloodstream. The remaining
phosphorus can be found in cells and tissues throughout the body. This form of
phosphorous is termed Organic phosphorus which occurs primarily in the form of
phospholipids.

Dietary Sources:
Protein-rich foods, such as meat, poultry, fish, eggs, dairy products, nuts, and
legumes are particularly good sources of phosphorus. Other sources include whole
grains, hard potatoes, dried fruit, garlic cloves, and carbonated beverages.
Functions:
1- Phosphorus helps in kidney function as it helps kidney to filter out waste 2- it
contributes to energy production in the body by participating in the breakdown of
carbohydrates, protein, and fats.
3- Phosphorus aids muscle contraction, including the regularity of the heartbeat, and
is also supportive of proper nerve conduction. It also helps reduce muscle pain after a
hard workout.
4- Phosphorus is needed for the growth, maintenance, and repair of all tissues and
cells, and for the production of the genetic building blocks, DNA and RNA.
5- Phosphorus is also a component of the phospholipids, fat molecules essential to
cell membranes; lecithin is the best-known phospholipids. It helps in fat
emulsification and in other body functions. Phosphorus is combined with the B
vitamins to assist their functions in the body; furthermore, phosphoproteins are
contained in many enzyme systems.

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6- Phosphorus is also needed to help balance and metabolize other vitamins and
minerals, including vitamin D, iodine, magnesium, and zinc.
7- It acts as a buffer for acid-base balance in the body by maintaining the pH of body
fluids, the cellular osmotic pressure,
8- This important mineral supports the conversion of niacin and riboflavin to their
active coenzyme forms.
Phosphorous absorption

Phosphorus absorption in the human body is proportional to the dietary intake, unlike
calcium, where absorption is inversely related to the logarithm of intake.

Phosphorus is absorbed more efficiently than calcium. Nearly 70 % of phosphorus is

absorbed from the intestines, although the rate depends somewhat on the levels of
calcium and vitamin D and the activity of parathyroid hormone (PTH), which
regulates the metabolism of phosphorus and calcium.
Taking large amounts of calcium from supplements can interfere with phosphorus
absorption
Phosphorus absorption may be decreased by antacids, iron, aluminum, or magnesium,
which may all form insoluble phosphates and be eliminated in the feces. Caffeine
causes increased phosphorus excretion by the kidneys.
Phosphorus deficiencies:
Phosphorus deficiencies are rare. Symptoms of phosphorus deficiency include loss of
appetite, anxiety, bone pain, bone fragility, stiffness in the joints, fatigue (excessive
tiredness), irregular breathing, irritability, numbness, weakness, and weight change.
In children, decreased growth and poor bone and tooth development may occur.
Excessive phosphorus:
Having too much phosphorus in the body is actually more common and more
worrisome than having too little of this mineral. Excessive phosphorus is generally
caused by kidney disease or by consuming too much dietary phosphorus relative to
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 Lipids & Minerals

dietary calcium. As dietary phosphorus increases, the need for additional calcium
rises as well. The delicate balance between calcium and phosphorus is necessary for
proper bone density and prevention of osteoporosis.
Too much phosphate can lead to diarrhea and calcification (hardening) of organs and
soft tissue, and can interfere with the body's ability to use iron, calcium, magnesium,
and zinc. Athletes and others taking supplements that contain phosphate, should only
do so very occasionally and with the guidance and direction of a health care provider.
Normal value: 2.4 - 4.1 mg/dl

Estimation of Phosphorous
1- Prepare 3 tubes as following:

Blank Standard Test

1ml reagent 1ml reagent + 10 µl st 1ml reagent +10 µl serum

2- Mix well and incubate for 10 minute at room temperature

3- Read absorbance at 400 nm
Calculation:
Phosphorous concentration = (Atest/Ast) × conc of st.
Conc of st. = 5 mg/dl

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Chloride
Chloride is one of the most important minerals in the blood, along with sodium,
potassium, and calcium. Chloride constitutes approximately 0.15% of human body
weight. It is primarily found in cerebrospinal fluid and gastrointestinal secretions.
Chloride is present in small amounts within bone.
Sources:
Most of the chloride in the body comes from table salt (sodium chloride) in the diet.
It is also found in many vegetables. Foods with higher amounts of chloride include
seaweed, rye, tomatoes, lettuce, celery, and olives. Potassium chloride is found in
most foods and is usually the main ingredient of salt substitutes
Functions:
 Chloride helps keep the amount of fluid inside and outside of cells in balance. It
also helps maintain proper blood volume, blood pressure, and pH of body fluids.
 Chloride is the major extra-cellular anion and contributes to many body functions
including the maintenance of osmotic pressure, acid-base balance, muscular activity,
and the movement of water between fluid compartments. It is associated with sodium
in the blood and was the first electrolyte to be routinely measured in the blood.
 Chloride ions are secreted in the gastric juice as hydrochloric acid, which is
essential for the digestion of food.
 With sodium and potassium, chloride works in the nervous system to aid in the
transport of electrical impulses throughout the body, as movement of negatively
charged chloride into the cell propagates the nervous electrical potential.
Absorption:
Chloride is absorbed primarily in the intestine and secreted through urine, sweat,
vomit, and diarrhea.
Chloride is absorbed by the intestine during food digestion. Any excess chloride is
passed out of the body through the urine. Chloride levels in the blood generally rise
and fall along with sodium levels in the blood.
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 Lipids & Minerals

The amount of chloride in the blood is indirectly regulated by the hormone

aldosterone, which also regulates the amount of sodium in the blood.
The amount of chloride decreases when the amount of sodium in the blood decreases,
and vice versa. The level of chloride in the blood is also related to the level of
bicarbonate. When the amount of bicarbonate decreases, the amount of chloride
normally increases, and vice versa.
Deficiency of Chloride (hypochloremia):
Deficiency of chloride is rare. Alkalosis may occur as a result of excessive loss of
sodium, such as heavy sweating during endurance exercise, and in cases of prolonged
vomiting and diarrhea. Symptoms include muscle weakness, loss of appetite,
irritability, dehydration, and profound lethargy.
Hypochloremia may result from water overload, wasting conditions, and extensive
bodily burns with sequestration of extra-cellular fluids. In a situation in which infants
were inadvertently fed chloride-deficient formula, many experienced failure to thrive,
anorexia, and weakness in their first year of life.
Excess Intake (hyperchloremia):
Excessive intakes of dietary chloride only occur with the ingestion of large amounts
of salt and potassium chloride. The toxic effects of such diets, such as fluid retention
and high blood pressure, are attributed to the high sodium and potassium levels.
Chloride toxicity has not been observed in humans except in the special case of
impaired sodium chloride metabolism, e.g. in congestive heart failure.
Normal value
Typical normal range is 96 - 106 mEq/L.

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Estimation of Chloride
1- Prepare 3 tubes as following:

Blank Standard Test

1ml reagent 1ml reagent Hg(SCN)2 1ml reagent Hg(SCN)2 +10 µl
Hg(SCN)2 +10 µl st serum

2- Mix well and incubate for 5 minute at 37 C

3- Read absorbance at 480 nm
Calculation:
Chloride concentration = (Atest/Ast) × conc. of standard.
Conc. of standard = 125 m mol/L

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 Lipids & Minerals

Magnesium
Magnesium is the fourth most abundant mineral in the body and is essential to good
health. Approximately 60-65% of total body magnesium is found in bone. The rest is
found predominantly inside cells of body tissues and organs. Only 1% of magnesium
is found in blood, but the body works very hard to keep blood levels of magnesium
constant.
Sources:
Green vegetables such as spinach are good sources of magnesium because the center
of the chlorophyll molecule (which gives green vegetables their color) contains
magnesium. Some legumes (beans and peas), nuts and seeds, and whole, unrefined
grains are also good sources of magnesium. Tap water can be a source of magnesium,
but the amount varies according to the water supply.
Functions:
1- Magnesium is needed for more than 300 biochemical reactions in the body. It
helps maintain normal muscle and nerve function, keeps heart rhythm steady,
supports a healthy immune system, and keeps bones strong. Magnesium also helps
regulate blood sugar levels, promotes normal blood pressure, and is known to be
involved in energy metabolism and protein synthesis. There is an increased interest
in the role of magnesium in preventing and managing disorders such as hypertension,
cardiovascular disease, and diabetes. Dietary magnesium is absorbed in the small
intestines. Magnesium is excreted through the kidneys.
2- Magnesium is an essential element in biological systems. Magnesium occurs
typically as the Mg2+ ion. It is an essential mineral nutrient for life, and is present in
every cell type in every organism. For example, ATP (adenosine triphosphate), the
main source of energy in cells, magnesium plays a role in the stability of all
polyphosphate compounds in the cells, including those associated with DNA and
RNA synthesis.

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3- Magnesium can affect muscle relaxation through direct action on the cell
membrane. Mg++ ions close certain types of calcium channels, which conduct a
positively charged calcium ion into the neuron. With an excess of magnesium, more
channels will be blocked and the nerve will have less activity.
4- In photosynthetic organisms Mg2+ has the additional vital role of being the
coordinating ion in the chlorophyll molecule.
5- Both Mg2+ and Ca2+ regularly stabilize membranes by the cross-linking of
carboxylated and phosphorylated head groups of lipids.
Absorption:
 Approximately one-third to one-half of dietary magnesium is absorbed into the
body. Gastrointestinal disorders that impair absorption such as Crohn's disease can
limit the body's ability to absorb magnesium. These disorders can deplete the body's
stores of magnesium and in extreme cases may result in magnesium deficiency.
Chronic or excessive vomiting and diarrhea may also result in magnesium depletion.
 Problems in the digestive tract are the most common cause of magnesium
deficiency. These digestive tract problems include mal-absorption, diarrhea, and
ulcerative colitis.
 Absorption is hindered by the presence of calcium, alcohol, protein, phosphates,
and fats. Vitamin D and lactose intake enhance magnesium absorption. Urinary
excretion of magnesium is carefully regulated by the kidneys.
 Antimicrobial or anti-infective agents such as neomycin, sulfonamides,
tetracycline, penicillin, tend to inhibit magnesium absorption.
Magnesium deficiency (hypomagnesaemia):
Because magnesium plays such a wide variety of roles in the body, the symptoms of
magnesium deficiency can also vary widely. Many symptoms involve changes in
nerve and muscle function. These changes include muscle weakness, tremor, and
spasm. In the heart muscle, magnesium deficiency can result in arrhythmia, irregular
contraction, and increased heart rate.

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 Lipids & Minerals

Because of its role in bone structure, the softening and weakening of bone can also be
a symptom of magnesium deficiency. Other symptoms can include: imbalanced blood
sugar levels; headaches; elevated blood pressure; elevated fats in the bloodstream;
depression; seizures; nausea; vomiting; and lack of appetite.
Inadequate magnesium intake frequently causes muscle spasms, and has been
associated with cardiovascular disease, diabetes, high blood pressure, anxiety
disorders, migraines, osteoporosis and cerebral infarction.
Early signs of magnesium deficiency: include loss of appetite, nausea, vomiting,
fatigue, and weakness. As magnesium deficiency worsens, numbness, tingling,
muscle contractions and cramps, seizures (sudden changes in behaviors caused by
excessive electrical activity in the brain), personality changes, abnormal heart
rhythms, and coronary spasms can occur.
Severe magnesium deficiency can result in low levels of calcium in the blood
(hypocalcemia). Magnesium deficiency is also associated with low levels of
potassium in the blood (hypokalemia).
Some medicines may result in magnesium deficiency, including certain diuretics,
antibiotics, and medications used to treat cancer (anti-neoplastic medication)
Excessive magnesium (hypermagnesemia):
The most common toxicity symptom associated with high levels of magnesium intake
is diarrhea. Magnesium toxicity can also be associated with very generalized
symptoms like increased drowsiness or sense of weakness.
Very large doses of magnesium-containing laxatives and antacids also have been
associated with magnesium toxicity.
Signs of excess magnesium can be similar to magnesium deficiency and include
changes in mental status, nausea, diarrhea, appetite loss, muscle weakness, difficulty
breathing, extremely low blood pressure, and irregular heartbeat.
Normal level: 1.7 to 2.2 mg/dL

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 Lipids & Minerals

Estimation of Magnesium
1- Prepare 3 tubes as following:

Blank Standard Test

1ml working 1ml working reagent + 1ml working reagent +10
reagent 10 µl st µl serum

2- Mix well and incubate for 5 minute at room temperature

3- Read absorbance at 520 nm

Calculation
Magnesium concentration= (Atest/Ast) × conc. of standard

Conc. of st. =

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 Lipids & Minerals

Iron

o Iron is an essential mineral and an important component of proteins involved in

oxygen transport and metabolism. Almost two-thirds of the iron in your body is
found in hemoglobin, the protein in red blood cells that carries oxygen to your body’s
tissues. Smaller amounts of iron are found in myoglobin, a protein that helps supply
oxygen to muscle, and in enzymes that assist biochemical reactions in cells.
o About 15 % of your body’s iron is stored for future needs and mobilized when
dietary intake is inadequate.
o The remainder is in your body’s tissues as part of proteins that help your body
function. Adult men and post-menopausal women lose very little iron except through
bleeding. Women with heavy monthly periods can lose a significant amount of iron.
Your body usually maintains normal iron status by controlling the amount of iron
absorbed from food
There are two forms of dietary iron: heme and non-heme. Iron in meat, fish, and
poultry is found in a chemical structure known as heme. Heme iron is absorbed very
efficiently by your body. Non-heme iron is not as well absorbed as heme iron. Flours,
cereals, and grain products that are enriched or fortified with iron are good dietary
sources of non-heme iron.
Absorption:
 Healthy adults absorb about 15% of the iron in their diet, but your actual
absorption is influenced by your body’s iron stores, the type of iron in the diet, and
by other dietary factors that either help or hinder iron absorption.
 The greatest influence on iron absorption is the amount stored in your body.
Iron absorption significantly increases when body stores are low.
 Absorption of heme iron is very efficient and not significantly affected by the
composition of your diet.

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Iron deficiency anemia: may result from a low dietary intake, inadequate intestinal
absorption, excessive blood loss, and/or increased needs. Women of childbearing age,
pregnant women, older infants and toddlers, and teenage girls are at greatest risk of
developing iron deficiency anemia because they have the greatest needs.
Iron and erythropoietin can also be lost with blood during dialysis, which can result
in an iron deficiency. Extra iron and erythropoietin are usually needed to help prevent
iron deficiency in these individuals.
Iron deficiency could also be caused by low vitamin A status. Vitamin A helps to
mobilize iron from its storage sites, so a deficiency of vitamin A limits the body’s
ability to use stored iron. This results in an ―apparent‖ iron deficiency because
hemoglobin levels are low, even though the body can maintain normal amounts of
stored iron.
Excessive iron: Iron has a moderate to high potential for toxicity because very little
iron is excreted from the body. Thus, iron can accumulate in body tissues and organs
when normal storage sites are full.
In children, acute toxicity can occur from overdoses of medicinal iron. It is
important to keep iron supplements tightly capped and away from children’s
reach. In adults high intakes of iron supplements are associated with constipation,
nausea, vomiting, and diarrhea, especially when the supplements are taken on an
empty stomach.
Normal value: 60-170 µg/dL

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