INTRODUCTION TO BIOCHEMISTRY

 His experience and contribution to the field of

BIOCHEMISTRY biochemistry paved way to a better understanding of
 The study of molecular basis of life metabolic pathways
 The study of BIOMOLECULES & the different
processes they undergo inside the human body Identification of Nucleic Acid as information molecules
 Concerned in PHYSICOCHEMICAL PROCESSES Oswald Avery, Colin Macleod and Maclyn McCarty (1944)
underlying digestion, absorption, circulation,  They extracted DNA from a toxic strain of
respiration, metabolism, growth & reproduction Streptococcus pneumonia and mixed the DNA with a
Freidrich Wohler (1828) non-toxic strain
 His experiment laid the foundation for modern James D. Watson and Francis H.C. Crick (1953)
biochemistry  They deduced the 3D structure of DNA
 He heated ammonium cyanate (inorganic  They discovered DNA replication process, which then
compound) to form urea (organic compound found transmits biological information to succeeding
in urine and blood) generation
 Demonstrated that organic compounds need not The central Dogma
necessarily be formed in living organisms  States that the information encoded in DNA is
transcribed to RNA and then translated to protein
TWO MAJOR BREAKTHROUGHS IN THE HISTORY OF BIOCHEM  DNA Transcription RNA translation CHON
 This is significant in understanding protein synthesis
Enzymes
and interrelated to cell function.
 catalysts of biological reactions amylase
BRANCHES OF BIOCHEMISTRY
Starch  glucose Molecular Anatomy
 different structures and properties of the different
biomolecules.
 Amylase from the example is the enzyme necessary
Biomolecules:
to degrade starch into its simplest form which is
 are any organic or inorganic matter which when
monosaccharide.
introduced into the body (eaten, injected or inhaled)
 This shows how significant enzyme is in any
will either positively or negatively affect vital life
biological reactions. With its discovery, better
processes.
understanding of metabolic processes was achieved
 E.g. food, medicine, chemicals, poisons.
Berzelius
 They also pertain to carbon-containing compounds
 formulated the general principles of catalysts that make up the various parts of the living cell and
 Lead to the recognition that ptyalin in saliva, pepsin carry out the chemical reactions that enable it to
of gastric juice and amylase of sprouted malt were grow, maintain and reproduce itself, and use and
biological catalysts store and energy.
 Biomolecules are also known as biopolymers.
Emil Fisher  They are macromolecules created by joining many
 studied the catalytic effect of yeast enzymes on a smaller organic molecules, or monomers via
simple reaction, the hydrolysis of sucrose condensation.
 Substrate + enzyme = intermediate compound Molecular Physiology
- Proposed the lock-and-key theory of enzyme  Concerned about the functions of the different
action (enzyme – lock; substrate – key). biological molecules
 This includes the idea that a particular substrate is Carbohydrates
acted upon by a specific enzyme.  organic compounds containing carbon, hydrogen and
- Almost all reactions that occur in living cells are oxygen, with a hydrogen-oxygen ratio of 2:1.
catalyzed by enzymes and thus proceed at very  These include simple sugars (monosaccharides) and
high rates their polymers (polysaccharides) and contain several
Carl Neuberg hydroxyl groups (polyalcohols).
 introduced the term Biochemistry in 1903 and thus Proteins
was named as the father of biochemistry.  biomolecules that contain an amino group and a
 His notable contribution to science includes the carboxylate group as well as a side chain.
discovery of the enzyme carboxylase. This is  These are made up of different amino acids joined by
necessary in the decarboxylation of pyruvic acid. an amide bond or a peptide bond and its shape is
 determined by the sequence of its amino acid  Allows pathways to be directed (under different
residues which is encoded by a gene. circumstances) to different end products
 The protein function depends on its 3D structure or 2 TYPES OF METABOLIC PATHWAYS
conformation 1. Linear metabolic pathway
Lipids  series of reactions generates a final product
 generally, water-insoluble organic compounds that  Each reaction is catalyzed by an enzyme
form the biological membrane.  A->B->C->D
 The simplest lipids are the fatty acids, long chain 2. Cyclic
hydrocarbons with a carbohydrate group at one end  Series of reactions regenerates the first reactant
Nucleic Acid
 are polymers composed of monomers called
nucleotides.

 Nucleotides contain a 5-carbon sugar, a heterocyclic
nitrogeneous base and at least one phosphate group.
PROCESSESS UNDERGONE BY BIOMOLECULES
A. DIGESTION
NUCLEOTIDES
- it refers to the breakdown of large foodstuffs into smaller
1. Ribonucleotides
particles
Sugar is ribose
- 2 forms
2. Deoxyribonucleotides
➢ Physical digestion – the mechanical conversion of big food
Sugar is deoxyribose
into smaller observable particles
WORK WITHIN CELLS ➢ Chemical Digestion – the conversion of big food particles
1. Mechanical Work into smaller absorbable forms with the participation of
 a change of location or posture of an organism, cell enzymes, hormones and digestive juices
or cellular structure
2. Osmotic or electrical work
B. ABSORPTION
 compounds or ions are often moved against a
- it refers to the diffusion or movement or nutrients and other
concentration gradient
ingested materials from the small intestines (jejunum) into
3. Synthetic Work
the blood stream
 a change in chemical bonds required to generate
- the process is facilitated by microvilli which are mobile,
complex molecules from simple precursors
fingerlike projections that increases the absorptive area of the
 The energy required to carry out this work can only
GIT
come from chemical bond energy. This is achieved by
coupling energetically favorable reactions to those
C. ASSIMILATION
that require a net energy input
- it refers to the selective uptake of specific nutrients by an
organ in the body
METABOLIC PATHWAYS
- in other words, the absorbed nutrients are not uniformly
Metabolic Pathways
distributed in the body
 are referred to as organized sequence of chemical
- For example:
reactions that are needed to extract the chemical
➢ Bones and teeth would take up more of the calcium and
bond energy from energy supplying compounds and
phosphorus
to synthesize different biological molecules.
 Enzymes ➢ Thyroid gland would take up most of iodine
o controls the metabolic pathways by ➢ Hair would take up zinc
catalyzing each of the steps in a pathway ➢ Bone marrow take most of the iron and copper to make
 Hormones RBC
o intercellular messengers that helps regulate ➢ Adipose tissues would take up most of the fat
the amount of substrate and enzymes ➢ Liver would take up most of the sugars
Importance:
 It permits control of the rate and direction of the
cellular activity D. UTILIZATION
 It prevents very large chemical bond energy releases - the process by which the absorbed nutrients are used by the
which would be damaging to cells different cells for a specific purpose or function
 It permits branch points
- e.g. ATP (adenosine triphosphate) – energy used by all cells  The eukaryotic cell’s genetic instructions are housed
in the body in the nucleus and carried out by the ribosomes
Prokaryotic cell
 does not include a nucleus or specialized organelles
E. INTEGRATION INTO TISSUES Based on Function:
- the process by which the absorbed nutrients are included or SOMATIC CELLS: make up the living structures of the
incorporated into the structural framework of the body like in body (body cell or autosomes)
the bones, muscles, teeth, hair, skin, joints, and ligaments SEX CELLS: germs cells ; involved in sexual reproduction
(sperm cells ovum)
F. BIOTRANSFORMATION AND METABOLIC DEGRADATION
- the process by which all harmful and potentially toxic Cell Structures
materials introduced into the body (like food, preservatives, Nucleus
food coloring, and chemicals like formalin) are inactivated or  Double membrane-bound control center of the cell.
detoxified by the liver into something non-toxic or even less  contains chromosomes, each of which consists of a
toxic thus, no significant harm is done on the body single molecule of DNA
- 2 forms  a chromosome contains thousands of hereditary
➢ Metabolic degradation – breakdown of complex units called genes
substances into simpler ones that act as active metabolites or  Spherical or oval shaped structure; Usually most
end products for energy production prominent feature of a cell
➢ Biosynthesis – combination of simpler substances to build Nuclear structures:
complex substances for cell repair, growth and reproduction Nuclear envelope - a double membrane that separates the
nucleus from the cytoplasm; Separates the genetic material
from the rest of the cell
G. EXCRETION Nuclear pores - numerous openings in the nuclear envelope,
- process by which metabolic wastes are finally expelled or control movement of substances between nucleus and
removed from the body cytoplasm
- these wastes when allowed to accumulate inside will destroy Nucleolus - spherical body that produces ribosomes (the
cells and tissues so these must be dispensed off fast MORE nucleoli, the FASTER in multiplying and dividing)
- Organs of excretion: ➢ Kidneys – urine - Small, discrete, spherical, densely staining
➢ Lungs – volatile acids in the form of CO2 structures made up of RNA; produces
➢ Skin – sweat (hypotonic NaCl) ribosomes
➢ GIT – stool or feces or undigested residue of food (excreted Genes - are the cell’s hereditary units, control activities and
through defecation structure of the cell
Chromosomes - long molecules of DNA combined with
protein molecules
THE CELL - long, linear chromatin materials combined with
THE CELL protein molecules
Cellular Diversity - contain the genes that represent all the traits of
an individual
 The average adult has nearly 100 trillion cells
- the genes are composed of segmented DNA
 There are about 200 different types of cells
Centrosome
 Cells come in a variety of shapes and sizes
- very small rounded bodies found on both ends
 Cellular diversity permits organization of cells into
of the nucleus
more complex tissues and organs
- regulates the rate of cell division and
GEN RULES:
multiplication
 There is only 1 nucleus in one cell EXCEPT RBC and
- Contains centriole
Plts (non-nucleated)
(centriole-containing) –adjacent to the nucleus and function
 Muscle cells are multinucleated
in the formation of the spindle apparatus during cell division,
 All organisms are composed of one or more cells
consists of a cylinder with 9 microtubules arranged
 All living cells came from other living cells
peripherally in a circle.
 Cells are the basic units of structure and function of
an organism Plasma Membrane
Types of Cells 1. Plasma membrane
Eukaryotic cells
 Protective layer
 contains a nucleus and organelles (more developed)
  separates the cell’s internal environment from the Membrane Permeability
outside environment  The cell is either permeable or impermeable to
 selective barrier certain substances
 Gives the size and shape of the cell  The lipid bilayer is permeable to oxygen, carbon
 plays a role in cellular communication dioxide, water and steroids, but impermeable to
 Flexible yet sturdy barrier glucose
 The fluid mosaic model - the arrangement of  Transmembrane proteins act as channels and
molecules within the membrane resembles a sea of transporters to assist the entrance of certain
lipids containing many types of proteins substances, for example, glucose and ions
 The lipids act as a barrier to certain substances
 The proteins act as “gatekeepers” to certain Factors Affecting Passage of Substances
molecules and ions  Degree of ionization- non-ionized form- are more
Layers and Composition diffusable
Carbohydrate- Mucopolysaccharide- strongest layer of the  Lipid solubility
cell membrane  Water solubility
Proteins (peripheral & integral) – gate keeper  Size of substance

Outer protein layer Peripheral protein 2 types of movements in the cell membrane
o attached to the inner or outer surface of the
membrane, do not extend through it Passive (transport) processes
Double layered lipid coat or lipid bilayer - substances move across cell membranes without the
o made up of phospholipids, cholesterol and input of any energy; use the kinetic energy of
glycolipids. individual molecules or ions
o This is the most important layer for selective - No need for carrier CHONS (proteins) as well as
permeability. energy or ATP
o The lipid bilayer is permeable to oxygen, - Osmosis
carbon dioxide, water and steroids, but Active (transport) processes
impermeable to glucose - cell uses energy, primarily from the breakdown of
Inner protein layer ATP, to move a substance across the membrane
o extend into or through the lipid bilayer - Requires specific carrier CHONS
Transmembrane proteins - Even against a concentration gradient
o span the entire lipid bilayer. Facultative or Facilitated Transport
o These act as channels and transporters to - Does not require energy
assist the entrance of certain substances, - Needs specific carrier proteins
for example, glucose and ions - Cannot move substances against concentration
 Lipids – selective permeability gradient
Active Transport
Structure of the Cell Membrane - cell uses energy
lipid bilayer - made up of phospholipids, - Requires specific carrier CHONS
cholesterol and glycolipids - Even against a concentration gradient
Integral proteins - extend into or through the lipid bilayer Passive vs. Active Processes
 Transmembrane proteins - span the entire Passive processes
lipid bilayer  substances move across cell membranes without
Peripheral proteins - attached to the inner or outer surface of the input of any energy; use the kinetic energy of
the membrane, do not extend through it individual molecules or ions
Glycoproteins - membrane proteins with a  No need for carrier CHONS
carbohydrate group attached that protrudes into  Osmosis
the extracellular fluid  No need for energy (ATP), no need for carrier
Glycocalyx - the “sugary coating” made up proteins
of the carbohydrate portions of the glycolipids and Active processes
glycoproteins  cell uses energy,
 Requires specific carrier CHONS
 Even against a concentration gradient
  cell uses energy, primarily from the breakdown of  Cytosol: mostly water
ATP, to move a substance across the membrane  Water: most abundant,
Facultative vs. Active Transport  Cytoplasm: all the cellular contents between the
Facultative or Facilitated Transport plasma membrane and the nucleus
 Does not require energy  Cytosol - intracellular fluid, surrounds the organelles;
 Needs specific carrier proteins marker is LDH
 Cannot move substances against concentration  - the site of many chemical reactions
gradient  - energy is usually released by these
Active processes reactions
 cell uses energy  - reactions provide the building blocks for
 Requires specific carrier CHONS cell maintenance, structure, function and growth
 Even against a concentration gradient CHEMICAL COMPOSITION:
Water
 Fixed and free state
Osmosis (M: 55-65% of the total body weight)
- Movement of solvent or water from a region of ( F: 45-55% of TBW)
lower to higher solute ( Infants: 70-80% of TBW)
Diffusion Fixed: integral part of the cell (for cell shape and size)
- Movement of solvent or water from a region of Free: freely passes from one cell to another for homeostasis
higher to lower solute Solutions and their Effects to the cell
ISOTONIC SOLUTION:
Types of gradient  has the same tonicity & osmolality as the blood
 Concentration gradient  Does not affect the amount of water in cells
 Eg. Isotonic saline
 inequalities in the solute concentration of 2
HYPOTONIC SOLUTION:
solutions separated be a semi-permeable
 has lower tonicity & osmolality than the blood
membrane
 drives water into the cell
 Electrical charge gradient
HYPERTONIC SOLUTION:
 differences in the net charge of the solute
 has greater tonicity & osmolality than the blood
Transport in Vesicles
 drives water out of the cell into the environment
 Vesicle - a small spherical sac formed by budding
CHO
off from a membrane
- primary source of energy (1gm = 4calories)
 Endocytosis - materials move into a cell in a vesicle
- Stored in the form of glycogen or starch
formed from the plasma membrane
FATS or LIPIDS
o three types: receptor-mediated endocytosis
- Serves as heat insulator & provides tissue elasticity
phagocytosis bulk-phase endocytosis
- Stored in the form of Triglyceride
(pinocytosis)
- Secondary source of energy
CHONS
 Exocytosis - vesicles fuse with the plasma
- Tissue-building ( 1gm = 4 calories)
membrane, releasing their contents into the - No storage form
extracellular fluid - most impt biomolecule, for structure
 Transcytosis - a combination of endocytosis and ELECTROLYTES
exocytosis - charged ions
K+, PO4-, - Intracellular fluid
Cytoplasm o potassium- cation
o PHOSPHATE ION - anion
1. Cytosol Na+, Cl-, - Extracellular fluid
 intracellular fluid, surrounds the organelles o Sodium – cation
 the site of many chemical reactions
o Chlorine- anion
 reactions provide the building blocks for cell
maintenance, structure, function and growth
Cytoskeleton
 Cytoplasm: all cellular components between the
 network of fibers extending throughout the
plasma membrane and nucleus
cytoplasm
 Water: we become susceptible to the effects of
 Also forms the major component of cilia and flagella
severe dehydration
  Microfilaments and microtubules transport to different
 network of protein filaments throughout the destinations
cytosol; three types according to increasing size: • Temporary storage depots for cellular secretions
microfilaments, intermediate filaments, and • Site of synthesis of large CHO
microtubules
 -provides structural support for the cell; Lysosome
 Cytosol - intracellular fluid, surrounds the organelles;  Single membrane bound structure.
the site of many chemical reactions; energy is usually  Contains digestive (proteolytic) enzymes that break
released by these reactions; reactions provide the down cellular waste and debris and nutrients for use
building blocks for cell maintenance, structure, by the cell.
function and growth  For intracellular defense mechanism
 Autophagy and heterophagy
Microtubules are often used by cells to hold their shape.  For intracellular defense mechanism (Digest
Microtubules are also the major component of cilia and substances ingested by phagocytosis; destruction of
flagella. The microfiliaments that are one third the size of microorganisms & of old cells
microtubles, help the cell to change or maintain its shape  Primary- have not yet engaged in any digestive
activity
 Secondary: sites of current or past digestive activity
2. Organelles
 Specialized & metabolically active Peroxisomes
structures/little organs within the cell;  Spherical or oblong structures
 smaller than lysosomes
Ribosomes  Production and degradation of H2O2
 Translate the genetic code into polypeptide chains.
 Degradation of certain fatty acids and amino acids
 Found attached to the Rough endoplasmic reticulum
 Detoxify several toxic substances
or free in the cytoplasm.
 60% RNA and 40% protein.
Mitochondrion
 where amino acids are joined together by PEPTIDE  Ultrastructure:
bonds to form polypeptide chains = new protein.  Outer layer continuous
Translate the genetic code into proteins
 Inner layer:
(polypeptide chains).
 Cristae - series of folds
Endoplasmic Reticulum
 Matrix - the large central fluid-filled cavity
- Transport of materails within the cell
 Site of cellular respiration
Rough Endoplasmic Reticulum  More prevalent in physiologically active cells:
 Network of continuous sacs, studded with muscles, liver and kidneys
ribosomes.  Self-replicate during times of increased cellular
 Manufactures, pro-cesses, and transports proteins demand or before cell division
for export from cell.  Site of ATP production
 Continuous with nuclear envelope.  The only organelle w/c contains DNA- used for self-
Smooth Endoplasmic Reticulum replication
 Involved in the synthesis of lipids, carbohydrate
metabolism, and detoxification of drugs and poisons. Vacuoles
 Metabolizes calcium. - Temporary dumping site for cellular wastes
- Storage of glycogen and fats
 Similar in appearance to rough ER, but without the
- spaces within
ribosomes.
- Inclusions are inert bodies that have no effect on
cellular activities
Golgi Complex
Inclusions
• Specialized portion of ER consists of 3-20 flattened,
membranous sacs called cisternae
Pigments
• modify, sort, and package
Exogenous origin
proteins and lipids
- picked-up from the outside of the body
made by the ER for
- e.g. Dust in the lung, Minerals in bones, lipochromes
 - and carotenoids form food  Values below 7 are acid in reaction
- H ions exceed OH ions
 The determination of H ion concentration of different
solutions may be done either by electrometric
Endogenous in origin method or by the use of standard buffers &
Hemoglobin- gives the red pigmentation of blood as has indicators (colorimetric).
several metabolites that could give rise to endogenous  Electrometric method – the use of pH meter
pigments seen in cellS  Colorimetric – standard buffers
Hemosiderin – metabolite of hemoglobin - golden brown - Methyl red
pigment seen in phagosomes in the liver and the spleen - Phenoptheline
Bilirubin – metabolite of hemoglobin - a yellowish pigment HYDROGEN & HYDROXYL
that is non-iron containing found in the liver cells  H & OH determines the acidity or alkalinity of a
Melanin – a brown-black pigment found in the skin and eye particular substance.
Lipofuchsin – a brownish pigment seen in the heart, liver, CNS  Hydroxyl – alkalinity
as the animal ages  Hydrogen - acidity
- may be found in the nucleus and the cytoplasm  Acids & bases w/c dissociate more readily are
- the origin and function of lipofuchsin is unknown capable of
Fat Droplets  liberating greater no. of H or OH ions thus called
- found as small globules within many cells strong acids or base
- most prominent in adipose tissues - Strong acid: hydrochloric acid
- they are stored as triglycerides (liquid at body - Strong base: sodium hydroxide
temperature  Those w/c ionize only slightly liberate comparatively
CRYSTALS less H or OH ions and are terms weak acids or bases
- usually found along steroid-secreting cells  Water is neutral since there is eual no. of H & OH
- found in the nucleus and cytoplasm liberated
- origin and function is also unknown  H2O H+ + OH-
GLYCOGEN Henderson-Hasselbach Equation
- found in the liver and skeletal muscles ● This fundamental equation relates the hydrogen
- found in small clusters called rosettes concentration in a solution of an acid or a base to its
- an individual glycogen measures 15-30 nm in dissociation constant and to the relative
diameter concentration of the dissociated and undissociated
- it is associated with the smooth endoplasmic forms of the acid or base.
reticulum within lysosomal particles

PH ANDCHEMISTRY
PH AND CHEMISTRYOFOF RESPIRATION
RESPIRATION

Buffer Substances
 are those w/c prevent the change of the reaction of a
Brownsted-Lowry soln. upon additional of small amounts of acids or
 The weak acid HA is an acid because it can donate a bases
proton  Buffer solutions consists of mixtures of weak acids &
 H ion concentration of solution is measured in terms their salts or weak bases & their salts
of pH value w/c is the logarithm of the no. of liters of  When an alkali is added to a buffer solution, the
a solution containing 1 grm of H ions excess solution to form water. Thus;
- NaOH + NaH2PO4 NA2HPO4 + H2O
Definition of terms  Upon the additional of acid however, the excess H
 All neutral solutions have the same pH value as ions combine w/ the negative ions to form weak
water acid. Thus,
 Values above 7 are alkaline o HCL = NaCl + H2CO3 (weak acid)
- OH ions exceed the H ion
  Prevent changes of reaction due to the power of  When 4 O2’s are bound to hemoglobin, it is 100%
minimizating the ionization of strong acid and bases saturated, w fewer O2’s it is partially saturated
by transforming them into weaker one  Hemoglobin’s affinity for O2 increases as its
 Strong acid or bases = water or weaker version of saturation increases
that particular substances.  Oxygen binding occurs in response to the P02 in the
 All body fluid except gastric juice, urine and milk are lungs
slightly alkaline, this is maintain by buffer substances.
Oxyhemoglobin Formation
 Blood pH – 7.4 – 7.45
 Acidosis – reduction  Oxygen molecule reversibly attaches to the heme
 Alkalosis – increased portion of hemoglobin
Chemistry of Respiration  Heme unit contains iron ( Fe+² ) which provides the
● Respiration is referred to as the exchange of gasses attractive force
between the outside air and the body.  O₂ + Hb ⇆HbO₂
● External respiration is the exchange occurring
between the outside air and the venous blood Maximum amount of 0, that can combine with HEMOGLOBIN
through the lungs. of blood
● Internal respiration is the exchange between the ● Normal Hb - 15 gms/100 ml of blood
blood and the tissues. ● Each gm of Hb can bind 1.34 ml of 02 (Hufner factor)
Physical Theory of Respiration ● The oxygen saturation of the RBC leaving the lungs is
● The exchange of gasses between the outside air, the around 96% while that of the venous Hgb is around
blood and the different tissues of the body, is 64%. This implies that 32% of the oxygen has been
governed by the physical law of diffusion. delivered to the tissues.
● Gas will flow from a higher to a lower tension. ● Total O₂ , bound with Hb :
● Tension is the pressure exerted by gas in solution. 15x1.34 x .32=6.4 ml O2 is supplied to tissues per 100ml of
blood passing through the capillaries
● Chemical control of respiration is exerted directly
upon the respiratory centers in the medulla and
upon the chemical receptors located at the
bifurcation of the common carotid arteries and the Factors affecting the dissociation of oxyhemoglobin
arch of the aorta. 1. Low oxygen pressure
● Chemical Control of Respiration  Whenever the pressure of O2 is low, the
- CO, is the main factor regulating the rate oxyhemoglobin rapidly dissociates into Hgb and Oz.
and depth of respiration.  НbO₂ →Hb + O₂
- Increasing the CO2 content of the blood - 2. High CO2 pressure
>increased rate and depth of respiration->  Increasing pCO2 - O, affinity of Hgb decreases +
increased pulmonary ventilation oxyhemoglobin dissociates (Bohr effect)
- Diminution of the pCO2 -> slow and shallow 3. Low pH
respiration - diminished respiration and  Acids (other than carbonic and lactic acid) increases
decreased CO2 elimination -> restoration of dissociation of oxyhemoglobin
pCO2 4. Rise of temperature
Oxygen Transport  Increases dissociation
 The blood plasma when exposed to oxygen pressure 5. Presence of electrolytes
 At low oxygen tension, Hgb gives up 0, more readily
present in the alveoli air can take oxygen only to the
in the presence of electrolytes than it does in pure
amount of 0.2 to 0.3 volume percent.
solution.
 Hemoglobin
 Hem – ion part Carbon Dioxide Transport
 Globin - protein  CO, is carried by the blood both in the cells and in
- Protein made up of 4 subunits the plasma.
- Every subunit contains a heme moiety COz is carried in the blood in 3 forms:
attached to a polypetide chain 1. in very small amount as dissolved H2CO;
 Hemoglobin molecules can transport up to four O2’s  the amount is not large but is important because any
change in its concentration will cause marked
alteration in the blood
2. as carbamino bound CO₂(R-NH₂ + CO₂ -> R-NH-СООН)  Takes place to during fasting & starvation where
 Formed with proteins (Hgb) there is increased mobilization of fat to provide the
3. as bicarbonate combined with cations, Na and K necessary energy reqt ->formation of ketone bodies
 At equilibrium, formation of carbonic acid is favored:  Occurs in severe diarrhea where there is loss of large
 At normal pH of blood, most of H,CO, is present in amount if Na
the form of bicarbonate: Metabolic Alkalosis
 Carbonic anhydrase is found in the muscles, parietal  Occurs when the alkali reserve is increased although
cells of the stomach participating in HCI production total base may remain unchanged
and in the kidney tubules catalyzing hydrogen  X’s vomiting & loss of large amount of Cl  increased
excretion. Na to bind w HCO3
 X’s use of diuretics & administration of large doses of
NaHCO3
Chemical Theory of Respiration Respiratory Acidosis (Hyperventilation)
1. The wall of the RBC is a membrane permeable to  Occurs in any condition in w/c there is interference w
water, CO2, carbonic acid, chlorine and hydrogen the exchange of gases w/in the lungs so that CO2 is
ions, but not to hemoglobin and plasma proteins and not adequately blown off.
only slightly to Na and K ions.  May happen in marked narcosis from drugs, CNS
2. Most of the Na ions in the plasma, while those of K depression from any cause, emphysema &
are in the cells. bronchiectasis
3. Most of the proteins in the RBC are combined with K, Respiratory Alkalosis (Hyperventilation)
the amount varying in the different stages of the  Produced in any condition causing hyperventilation,
cycle. when this is not the result of interference with the
4. In the RBC (not in the plasma) there is an enzyme, gaseous exchange in the lungs
the carbonic anhydrase, which hastens the  Occurs among nervous Px who are breathing rapidly
transformation of carbon dioxide and water into due to some frightening symptom or situation
carbonic acid and vice versa.  Can be seen in high fevers, CNS lessons & anoxia of
the cardiac type or due to high altitudes
Acid – Base Balance  The increased ventilation blows off large amounts of
 The acid-base balance depends upon the ration of CO2 so that the plasma carbonic acid concentration
H2CO3 to BHCO3 (1:20) is decreased
 Normal metabolic activities of the body  production
of relatively large amounts of acids Buffer system of the blood
 including carbonic, sulfuric, phosphoric & organic A. Buffer action of hemoglobin
acids, like lactic and hydroxybutyric acids  The buffering effect is due to the imidazole group of
 Sulfur & phosphorus containing proteins  (oxidized) histidine
give rise to H2SO2 and H3PO4  Exerts is buffering effect on H2CO3
 Fruits & vegatbales (rich in positive radicals like Na, H2CO3 →H+ + HCO3-
K, Ca) liberate potentially basic substances  H+ is buffered by Hgb and HCO3- diffuses out in the
 The maintenance of this normal pH is ;brought about plasma in exchange for chloride
by several factors
i. The buffer systems of the blood B. Buffer action of bicarbonate
ii. CO2 elimination through the lungs  Bicarbonate is the major buffer of the extracellular
iii. Renal excretaion of acids and bases fluid
 Under normal condition, urinary pH is about  Exerts buffering effects on fixed acids
6.0  There is more bicarbonate found in the extracellular
 Under certain conditions the pH of the urine fluid than other buffer component
may vary from 4.5 to 8.2  There is limitless supply of CO2
iv. Renal formation of ammonia – base convertion  There are physiological mechanisms which maintain
the extracellular pH function by controlling the
Abnormalities of Acid-Base Balance bicarbonate or CO2 concentration
Metabolic Acidosis  The HCO3-/H2CO3 buffer operates in conjunction
 Produced whenever available base is decreased with Hgb
although the total base may remain unchanged  As long as adequate amount of bicarbonate is
present, it can dispose of the fixed acids efficiently
 - Alkali reserve – the amount of bicarbonate  Failure of formation of NH3 may be the cause of
that serves as a measure of the alkali acidosis and dehydration in the lower nephron
available for neutralization of fixed acids nephrosis
 True plasma  Alterations of the carbonic acid factor calls for
- as pCO2 is increased there is an appreciable compensation by the kidneys
increase HCO3- so that the pH does not fall  Alterations of the bicarbonate factor calls for
so rapidly compensation by the lungs
- As the pCO2 decreases, the HCO3-also
decreases thus preventing the expected rise
in pH
Nucleic acids
NUCLEIC ACIDand heredity
AND HEREDITY
Carbon dioxide elimination through the lungs
Factors: Nucleoprotein
1. The sensitivity of the respiratory center to slight changes of - Conjugated proteins
CO2 pressure and the H+ concentration - Proteins + nucleic acids
 If CO2 in increased by 1-5 mmHg it will increase 1. Protein conjugated with nucleic acid
pulmonary ventilation eliminating the excess CO2; 2. Principal constituent of hereditary material in
same for H+ chromosomes
 Low pCO2 and H+ leads to hypoventilation, CO2 is 3. Found in ribosomes
retained until it comes back to normal.
Functions:
2. The diffusibility of CO2 from the blood thru the pulmonary ● duplication
epithelium into the alveoli air ● Storage, expression and transmission of genetic
information
Renal excretion of acids and bases ● Undergo mutation
 If the fixed acids that have been temporarily
neutralized by the HCO3-, are not eliminated, it will TYPES OF TRAITS
be taken cared of by the kidneys.
 Urinary pH is about 6.0 and the pH of blood is 7.45 – 1. DOMINANT TRAIT
the difference in pH represents the amount of acid -majority of the offspring
the kidneys remove from the blood -e.g. black hair is dominant over blond hair
 Urinary pH may vary from 4.5 – 8.2 – our kidneys can
excrete excess acids and bases making it the most 2. RECESSIVE TRAIT
important regulator of acid base balance -minority of offspring’s
 Uses HPO4/H2PO4 -disappear and reappear
Renal formation of ammonia
 Urinary ammonia is formed in the distal portion of TYPES OF EXPRESSION
the uriniferous tubules: the site of acidification of
urine 1. PHENOTYPES
 Ammonia is derived from the amide grp of glutamine -physical observable
(60%) and from amino acids (40%) -e.g. color of eyes, bridge of the nose, dimples
 Factors that stimulate the formation of ammonia 2. GENOTYPE
- Diminished bicarbonate of the blood and -non-observable, non-physical -e.g. IQ, talent, allergy
glomerular filtrate
- Increased hydrogen ion concentration NUCLEOPROTEINS
 This prevents the accumulation of H+ and allows -protein combined with nucleic acid
continued exchange of H+ with Na+ -found in cytoplasm
 The amount of Na+ reabsorbed in the distal tubule -present in all living cell
reflects the amount of both H+ and NH4+ ions in the -constituent of heredity
urine -duplication
 Thus the fixed alkali (Na+) of the blood is conserved. -tissues with closely packed cells and big nuclei
 Renal secretion of ammonia is more significant than -associated with chromosomes
acidification
PROPERTIES OF NUCLEOPROTEINS
-Acidic
-Soluble in alkalies with which they form salts Functions of Nucleoproteins and Nucleic acids
A. To reproduce their own kind (duplication)
HYDROLYSIS OF NUCLEOPROTEINS B. To store, express and transmit genetic information
C. The undergo mutation

4 MAJOR DIFFERENCES BETWEEN

RNA AND DNA
● Ribose is the sugar unit in RNA
● Thymine is replaced by uracil in RNA. Uracil pairs
with adenine
● RNA.is single stranded, thus it does not contain equal
amounts of specific bases
● The RNA is much smaller than the DNA (from 75
NUCLEIC ACIDS nucleotides to a few thousand nucleotides)
-Macromolecules
-first discovered in the nuclei of cells Deoxyribonucleic Acid (DNA)
-direct the activities of a cell and its reproduction Structure:
● Hydrogen bond, Phosphate group Deoxyribose sugar
Components ● Agiant molecule consists of repeating units of
- Elementary components: 15 - 16% N; 9 – 10% P nucleotides
● Double stranded: coiled together around a common
axis
NITROGENOUS BASE ● Spiral Staircase: double helix
1. Pyrimidine 2. Purine ● The 2 strands are antiparallel
● Sugar-PO4:side of ladder
PYRIMIDINE ● N bases connected by H bonds: Rungs/steps
- 6-membered ring structure - Include: DNA: Mechanics of formation
A. cytosine – 2 – oxy-4-aminopyridine ● Complementary base pairing The 2
B. uracil – 2,4 – dioxypyrimidine ● strands are held together by complementary base
C. Thymine – 5 – methyl – 2,4 - dioxypyrimidine pairing.
● A=T:G=C
PURINE BASE ● There are always the same number of A bases as T
-Includes pyrimidine and imidazole ring bases, and G as C.
-Include Putting it all together
Adenine – 6 – aminopurie ● Phosphate group attaches to the 5' carbon of the
Guanine – 2-amino-6-oxypurine deoxy-pentose sugar
II. SUGARS III. PHOSPHORIC ACID ● The nitrogenous base attaches at the 1' position of
- Ribose -H3PO4 the deoxy-pentose sugar
- Deoxyribose -H2O3POH ● Two or more nucleotides can be joined (together
through phosphodiester bonds
NUCLEOSIDE - Uses β – glycosidic linkage ● Phosphodiester bonds link the 5 c a r b o n atom fo
-SUGAR +BASE = NUCLEOSIDE the 2-deoxy-pentose from one nucleotide with the 3'
carbon atom the 2-deoxy-pentose bf another atom
Purine nucleosides -C1 of sugar to N9 of purine ● The resulting chain forms the sugar
Pyrimidine nucleosides -C1 of sugar to N1 of pyrimidine ● phosphate backbone of the DNA molecule
● Adenine (A) pairs with thymine(T)by2 hydrogen
NUCLEOTIDE bonds
-fundamental sub-unit ● Guanine (G) pairs with cytosine© by3 hydrogen
-Basic structural unit of nucleic acids bonds
-It is the monomer for nucleic acids - ● Adenine: thymine and Guanine: cytosine (base pairs
SUGAR+BASE+PHOSPHATE have identical width, creating the uniform with found
Includes: in the DNA helix
o Adenylic acid o Guanylic acid o Thymidylic acid o
Cytidylic acid o Uridylic acid
 ● The base pairs lie 3.4 A apart and the helical turns ● RNA molecules are classified according to their
repeat every 34 A. therefore there are 10 structure & function
complementary sets of base pairs to every helical
turn RNA: Roles
● The two strands of DNA are complementary rather ● Serves as the carrier of genetic information to the
than identical and run antiparallel to each other in a site of protein synthesis (mRNA)
double helix ● Essential component of the ribosomes
● Serves as the genetic material for some viruses
DNA: CHARGAFF'S Rule
● The base composition of the DNA of all organisms is RNA: Types
CONSTANT
● The amount of purine bases is always EQUAL to the
amount of pyrimidine bases A=T : G=C

DNA: FUNCTION
● Stores all the information about the proteins that
make-up the organism (genetic material).
Chromosome: densely packed DNA during mitosis mRNA:
Chromatin: less densely packed DNA (accessible to the -carries the genetic code the cytoplasm for the formation of
transcription and replication of enzymes) protein
Heterochromatin / Nuclear chromatin: consists of densely
packed DNA: darkly stained areas of the nucleus tRNA:
Euchromatin / Parachromatin: not tightly packed DNA; lightly - transfers amino acid molecules to the ribosomes during
or poorly stained areas in the nucleus protein synthesis
- smaller
The genomic structure
● Each DNA molecule is organized into discrete units rRNA:
called chromosomes.The total genetic information - constitute 40-50% of the ribosomes (attached to the ER for
stored in chromosomes are referred to as the protein synthesis)
genome of the organism - Function si structural and may also be catalytic for some
● The human genome contains 3x10⁹ nucleotide base translation reactions
pairs approximately packages into 23 pairs of
chromosome The Central Dogma (by Francis Crick in 1957)
● 22 pairs of chromosomes are independent of sex, ● Explains the flow of genetic information within a cell
they are called autosomes ● Also known as “one gene-one protein hypothesis”
● The remaining chromosomes determine sec and may ● The genetic information contained in one gene of a
be X or Y DNA molecule is used to make one molecule of
● The total chromosomes count in a human is 44 mRNA by a process known as transcription
autosomes and two sex chromosomes , XX for ● The genetic information in that mRNA molecule is
femaleand XY f o r males then used to make one protein by a process known
as translation

Ribonucleic Acid (RNA) Protein Synthesis

Structure: I. Transcription
● Single-stranded/helix ● The process by which a segment of the DNA is cut off
● Ribose-POn: backbone or nicked from the molecule by the enzyme - RNA
● Bases are variable and stick out from the backbone; polymerase
Ratio is NOT always 1:1 ● The detached portion together with its
accompanying nitrogenous base will serve as a
template for the formation of a complementary
● Can have a 2° structure: step-loops strand finally resulting to the formation of a mRNA
● Can have a 3° structure: pseudoknot, cloverleaf (occurs in the nucleus)
 ● To reconstruct the DNA molecule: OKAZAKI ● Universal- All plants, animals and bacterial cell have
fragments are put together by ligase the same codon to specify each amino acid
● mRNA leaves the nucleus and goes to the ribosomes, ● Degenerate-More than one triplet can code for a
it carries with it the codon particular amino acid
● Continuous
II. Translation Non-overlapping
● the process by which tRNA accepts the codon carried Adjacent codons do not overlap
by the mRNA, reacts, translates and decodes the
message Three Processes involved in the Biosynthesis of Proteins
● pertains to the production of the 20 amino acids 1. Initiation
a. The codon AUG or GUG (AUG is more
III. Formation of polypeptide Chain common)signals the start of protein
● amino acids in the cytoplasm are activated by synthesis
combining with ATP b. Once the correct starting point has been
● Amino Acid + ATP Amino acyl tRNA synthetase identified, a special initiator tRNA binds to
Amino acyl Adenylate the ribosome
● the tRNA will transport individual amino acids to the 2. Elongation – after the initiator tRNA attaches to the mRNA
ribosomes based on the arrangement which follows codon, the elongation of the polypeptide chain starts
strictly the dictates of the codon a. The formation of the peptide chain which assembles
one amino acid at a time
The Genetic Code b. Translocation – the shift of a ribosome along mRNA
● Genetic information from DNA in encoded in the from one codon (three bases) to the next codon
mRNA as a sequence of nucleotides during translation
● The genetic code is the sequence of three bases (or c. The process of elongation continues as the ribosome
triplet), called a codon, that specifies the amino acid moves along (translocates) the mRNA, one codon at
order for the synthesis of proteins a time
● Example 3. Termination
Codons (base sequence) in mRNA a. Protein synthesis stops when a ribosome encounters
Translation the codon UGA, UAA or UAG
Amino Acid sequence
● Thus, a protein with 200 AA = 200 codons
o 200 x 3 = 600 nucleotides
Some Genetic Diseases
Codon – a sequence of three bases in mRNA that specified a A. Down’s syndrome – is the leading cause of mental
certain amino acid to retardation, occurring in about 1 of every 800 live births.
be placed in a protein. A few codons signal the start or stop of Mental and physical problem including heart and eye defects
transcription are the result of the formation of three chromosomes, usually
chromosome 21, instead of a
Anticodon – the triplet of bases in the center loop of tRNA pair
that is complementary to a codon on mRNA
B. Sickle-cell anemia – a defective hemoglobin from a
mutation in a gene on chromosome 11 decreases the oxygen-
carrying capacity of red blood cells that take on a sickle-
shape, causing anemia and plugged capillaries from red blood
cell aggregation

C. Galactosemia – absence of the transferase enzyme

TC – Termination codon or nonsense codon required for the metabolism of galactose-1-phosphate,
- They do not encode any amino acids leading to cataracts
- Act as signals to indicate where the synthesis of a protein and mental retardation
molecule is to end
D. Cystic fibrosis – the most common inherited disease, thick
mucus secretions make breathing difficult and block
Characteristics of the codon pancreatic functions
  Non protein biochemical
E. Familial hypercholesterolenemia – a mutation of a gene on  Enzyme reaction
chromosome 19 characterized by high cholesterol levels  Catalytic as a co-substrate
leading to early coronary heart disease in 30-40 year-old  Organic molecule is smaller than protein
persons Metaloenzymes
 Same with activators
F. Muscular Dystrophy (Duchenne) – one of 10 forms of MD  Inorganic activators as part of enzyme molecules
caused by a mutation in the X chromosome occurring in about Substrate
1 of 10,000 males due to the low or abnormal production of  Acted upon by enzyme and converted into new
dystrophin by the x gene, a muscle-destroying disease substance
beginning at about age 5 with death by age 20 Products
 Substance derived form transformed substance
G. Hemophilia – one or more defective blood clotting factors Activators
leading to poor coagulation, excessive bleeding and internal  Metabolic regulators of a given reactions of series
hemorrhages  Inorganic molecules cofactors
Prosthetic group
H. Tay-Sach’s disease – a defective hexosaminidase A, causing  Coenzyme cannot be removed
an accumulation of gangliosides resulting in mental Holoenzyme
retardation, loss of motor control and early death  True enzyme
 Coenzyme + enzyme
I. Huntington’s disease – a genetic disease appearing in
Apoenzyme
middle age affecting the nervous system that leads to total
 Without cofactos
physical impairment, result of a mutation in a gene on
 Apoenzyme + coenzyme = haloenzyme
chromosome 4, which can now be mapped to test people in
families with HD
4 Existing Structures
1. Primary structure – refers to the sequence of amino acids
joined by peptide bonds (lining)
ENZYMOLOGY
2. Secondary structure – conformation of the steric
arrangement or conformation of the segments of polypeptide
ENZYMOLOGY
chain
- It refers to the science of enzymes to the diagnosis
- if it is disrupted the enzyme will not function
and treatment of diseases
En – in ; zyme - yeast
3. Tertiary structure – arises from the interactions among side
ENZYMES
chains/groups of the polymer chain; folded structure of an
 Substance that catalyzes a given chemical reaction,
enzyme
cellular catalyst
 They are biologic catalysts that causes reactions in
the body to take place
4. Quaternary Structure – refers to the relationship between
 There are over 1,500 enzymes and many of which subunits
catalyzes the same reactions - Subunits perform specific functions
o The secondary and tertiary structures are the most
CHARACTERISTICS OF AN ENZYME important configurations of the enzyme because these
 One of the most complicated type of proteins in structures are responsible for the characteristics such as
terms of both structure and functions coiling and folding resulting to conformational structure
 Proteins in nature; easily denatured with varying
molecular weight and masses Active Site
 Enzymes are amphoteric – base and acid  Refers to the area or portion of an enzyme in which
 Enzymes operate in high rates the substrate is attached with the enzyme molecule
 Catalyzed are frequently reversible  It is where the transformation of the substrate takes
 Operate with assistance of non-protein cofactor place

Coenzyme Classification of Enzymes

 Vitamin by nature - Based on catalytic activity of an enzyme
 Lipase – catalyze Galactosidase
o Oxidoreductases - oxidase the hydrolysis of
o Transferases - transfer lipid
o Hydrolases - hydrolysis
o Lyases - breakdown LYASES
o Isomerases - conversion  Enzymes responsible for splitting molecules (lysis)
o Ligases – combination  Bonds broken are
 No water involved
OXIDOREDUCTASES o C-C bond
 Enzymes catalyzing oxidation and reduction  Assayed in disorders of skeletal muscles
reactions Examples
o Reduction – addition of hydrogen to a o Aldolase – necessary for spitting aldol
double bond o Glutamate decarboxylase – catalyze the removal
o Oxidation – removal of hydrogen to cleave a of carbon dioxide from glutamate to another
double bond substance
 Older names are dehydrogenases and oxidases ISOMERASES
 Assayed for investigation of gives information  Enzymes responsible for the conversion of one
regarding heart attacks and liver problems isomer to another
Examples of oxidoreductases  It involves the transformation from
Oxidases – oxidation o Cis-trans
 Glucose oxidase - catalyze the oxidation of glucose o L-D forms
 Cytochrome oxidase- catalyzed the oxidation of o Aldehyde to ketone
cytochrome  All reactions are reversible
 No clinical importance
Dehydrogenase - removal - Examples
 LDH - catalyze the removal of hydrogen from lactase o Glucose PO4 isomerase
ion o Ribose PO4 isomerase

TRANSFERASES LIGASES
 Enzymes that move and interact group of atoms from  Enzymes causing bond formation between two
one molecule to another (amine or PO4 group) molecules to form a longer molecule
 Gives important information about liver damage o o Ligase enzyme
Examples of transferases o Amino-acyl-tRNA synthetase – activates amino
Aspartic aminotransferase (AST) – catalyzed the transfer of acids before incorporation to the polypeptide
amino acid from aspartic chain
(Serum glutamate oxaloacetate transaminase (SGOT) )
Alanine aminotransferase (ALT)
( Serum glutamate pyruvate transaminase (SGPT) ) ENZYME NOMENCLATURE
1. Each enzyme was designated according to the
Subtype reaction it catalyzes
transaminase – transfer amino group from one another Example: oxidation of glucose – glucose oxidase
Kinase – transfer phosphate group from ATP to given ADP 2. It is customary to identify enzymes by adding the
suffix “ase” to the group upon which the enzyme acts
HYDROLASES Example: Urea – urease
 Enzymes involved in the splitting of molecules with Uric – uricase
water as a part of the reaction process Phosphate esters – phosphatase
 3 groups of hydrolases Lipid – lipid esters
Esterases (lipid) Peptidases Glycosidases Lactose – lactase
(protein) (carbohydrate) Starch – amylase
ACP Leucine Amylases 3. Naming of enzymes by the use of their empirical names
aminopeptidase Example: trypsin, pepsin
ALP Trypsin Amylo-6- 4. Standard system of identifying enzymes
glucosidase - Formulated by IUB and IUPAC
Cholinesterase pepsin Glucoside
 Systematic name o Relative substrate specificity
 Describe the nature of the reactions catalyzed
 Unique numerical code designation (consists of 4
members separated by periods) B. HETEROENZYMES
 Prefixed with letter E.C. (Enzyme Commission) • Same enzymatic activity, which are specie specific for
 E.g. E.C. 3.1.3.1. – ALP different biological species
E.C. 3.1.3.2 – ACP e.g. LDH of rabbits and humans
o 1st digit – denotes the class of the enzyme C. ALLOENZYMES
(hydrolase) • Genetically transmitted enzymes
o 2nd digit – denotes the sub-class of the enzyme • Important in defining the biochemical characteristics
o 3rd digit – denotes the sub sub-class of individuals
o 4th digit – specific serial number given to each • Present only in some selected individuals of the
enzyme within its sub sub-class same species
▪ This approach removes all ambiguity about the • Practical value in forensic medicine and genetics
enzyme’s identity
Trivial names ORIGIN OF PLASMA ENZYMES: CLASSIFICATION OF ENZYMES
 A.K.A. non-specific , practical name, working name IN THE BLOOD
 Identical to systematic name and often a
simplification of it A. Plasma Specific Enzymes
 Suitable for everyday use • Generally secreted by liver into the plasma
 Uses acronyms and abbreviations • Enzymes exert function in plasma
• Orthophosphoric monoester phosphorylase - ALP • Examples
o Blood clotting mechanisms
o Complement system and those connected with
ENZYME VARIANT fibrinolysis
- These are the several distinct forms of enzymes o Thrombin, factor XII (Hageman factor), Factor X
- Important in the diagnosis of specificity (Stuart factor)
o Precursors (plasminogen activators)
A. ISOENZYMES
 The multichained enzymes
 Enzymes of similar activity typically appearing in B. Non-plasma specific enzymes
specific tissue, organs and cell organelles of • Enzymes that do not have specific function in plasma
organisms and the same species • The plasma lacks activators or coenzymes which are
 Specifically located in tissues necessary for enzyme activity
 The site of a specific isoenzyme is found and • 2 classes
restricted to only one tissue o Enzyme of secretion
 Example: Lactate dehydrogenase: A and M ▪ These are normally secreted enzymes like
o Contains H and M subunits (polypeptide chains) AMS
o The subunits interact together for a reaction to ▪ Enzymes secreted in plasma at a very high
occur rate but are rapidly disposed off to normal
o H4 – LD1 – heart, RBC, and renal tissues excretory channels thus concentration in
o H3M – LD2 – heart, RBC and renal tissues plasma is maintained at low and constant
o H2M2 – LD3 – lungs, lymphocytes, spleen, level
o Enzymes associated with cellular
pancreas
o HM3 – LD4 – liver, skeletal muscle metabolism
▪ Enzymes that carry out their functions
o M4 – LD5 – liver, skeletal muscle
within the cells in which they are formed
 Characteristics
E.g. CK in heart and ACP in prostate gland
o Charged molecules – shown in electrophoresis
o Mobility in Ion Exchange Resin
Enzymes based on distribution
o Response to activation and inactivation process
A. Unilocular Enzymes
 E.g. ACP (RBC) – not inhibited by 2%
• These are enzymes found only in the cell sap
formaldehyde ACP (prostate) – inhibited by • Found only in one location
2% formaldehyde
B. Bilocular enzyme
 • These are enzymes that are found in the • The rate of reaction dependent on substrate
mitochondria and cell sap concentration and on enzyme concentration
Where:
E = enzyme that represents a true catalyst B. Zero Order Kinetics
= not changed in the reaction • The rate depends on the enzyme
S = substrate upon which the enzyme acts concentration and independent of substrate
P = the reacted substrate concentration
= product that represents a changed molecular
species of substrate C. Enzyme Concentration
ES = the postulated enzyme – substrate complex a. Direct relationship
b. An increase in the enzyme concentration result to an
increase in the catalytic activity of the enzyme
I. Factors Affecting the Binding
D. Temperature
A. Energy – this refers to the activation energy a. Optimum temperature – the point at which the enzyme
B. Molecular compatibility – E + S = commonness and molecule is capable of catalyzing the substrate with regards to
sameness between enzyme and substrate temperature requirement
C. Space availability – refers to the number of enzymes or i. An increase of 10C in temperature results in
substrates that can be reacted doubling the rate of enzyme activity
D. Specificity – refers to the particular enzyme catalyzing a ii. 30-37C or 37-40C – optimum temperature
specific substrate iii. 60-70C – enzyme undergoes inactivation and
denaturation
II. Factors Affecting E and S Combination iv. Further increase in temperature leads not to
further increase in the rate but loss of enzymatic
A. Lock and Key – refers to the active site being assay
complementary in shape and size of the substrate v. Some are stored at refrigeration temperature (2-
B. Induced Fit model – refers to the enzyme changing in 8C)
shape during binding with substrate. After binding, the shape
of the enzyme complements with the binding site b. Increased rate in
i. Increasing movement of molecule
III. Factors influencing Enzymatic Reaction ii. Increasing rate at which internal cellular collision

A. Substrate concentration a. direct relationship c. Q10 value – refers to the increased reaxtion rate for every
b. An increase in the concentration of substrate results to an 10C increase (rate of reaction is doubled)
increase in the rate of enzyme activity
c. No free binding site E. pH – Hydrogen ion concentration a. optimum pH – the
point at which the reaction rate is greatest
B. Time i. at pH 7-8, many enzymes show maximum activity
• This refers to the condition when the enzymatic reaction ii. pepsin is active at 1.5 and ALP at 10.5
is allowed to take place
• If the catalytic activity of an enzyme on the substrate is
fast, it results to a shorter enzymatic reaction time F. Activators
thereby the enzyme is freed and can act again on the a. Required for full enzyme activity
remaining substrate b. These metal activators or inorganic entities help bind the
substrate tp the active site by forming ionic bridges
2 Phases of Enzyme Reaction c. These help substrate in orientation so it is attached to the
protein at the proper point nd in the correct configuration
A. First Order Kinetics
• Enzyme concentration is fixed and the substrate G. Inhibitors
concentration is varied a. Substances that decrease the rate of enzyme reaction if
• The rate of reaction is almost directly proportional to these are present in the reaction system
substrate concentration at low values (lower b. Functions
substrate concentration than enzyme) i. Binds to the active site, blocking the access of the
substrate to the enzyme (competitive inhibition)
 ii. Binds elsewhere on the enzyme causing change in 5. Enzyme activities are also regulated by isoenzymes
shape that interferes with substrate binding (non- (isozymes), enzymes that catalyze the same reactions but
competitive) vary slightly in structure.
iii. Uncompetitive – inhibitors bind with the ES
completely; no product formed The water- soluble vitamins
Vitamin Coenzyme Enzyme Deficiency Metabolism
function of
Enzyme Denaturation
Thiamine thiamine Reductase Beriberi, fatigue, carbohydrat
• It refers to the disruption of the structure of enzyme (B1) pyrophosphat depression e
molecule (3-dimensional structure) that leads to the e TPP
Riboflavi flavin adenine Reductase Cracked lips, scaly Carbohydrat
loss of enzyme activity skin, sore tongue
n (B2) dinucleotide e and lipid
• Denaturation may be reversed if the reaction process (FAD) and
has not gone too far and if the denaturing agent is flavin
mononucleoti
removed de FNM
• Denaturing Conditions Niacin nicotinamide Reductase Pellagra, Carbohydrat
o Elevated temperature (nicotinic adenine Dermatitis; e, lipid and
acid B3) dinucleotide glossitis; cataracts protein
▪ Weakens the stabilizing bonds (NADH)
▪ Above 60C Pyridoxin pyridoxal Aminotran Skin lesion- protein
sferase serobic/ grisy
o Extremes of pH e (B6) phosphate
dermatitis
PPT
▪Causes unfolding of enzyme molecule Cobalami nicotinamide Isomerase Megaloblastic Krebs cycle
o Radiation n (B12) adenine anemia,
-from dinucleotide neurodegeneratio
o Frothing animal and n
(NADH)
animal
product
Types of Enzyme Specificity Ascorbic Vitamin C Hydroxylas Scurvy – bleeding
acid e gums, slow-
healing wounds,
1. Absolute specificity – when an enzyme act and mental disorders
catalyze 1 unique reaction Biotin biocytin Carboxylas Not common Krebs cycle
e deficiency
2. Group Specificity – when some enzyme act on because of wide
different substrate that belongs to the group spread in
nutritious food
3. Stereoisomeric – when an enzyme acts only on Folic acid tetrahydrofoli Methyltra Megaloblastic protein
specific isomer (cysts, trans, L ,D isomers) (vitamin c acid THF nsferase anemia
M)
Pantothe coenzyme A acyltransfe Not common Krebs cycle
Units of Measurements – proposed by the IUPAC and IUB nic acid rase deficiency
(B5) because of wide
spread in
A. International Unit (IU) nutritious food.
• Defined as the amount of enzyme which catalyzes the Weight loss

conversion of 1umol of substrate in 1 minute

• Reported in IU/liter of sample
B. Katal – most commonly used * B1, B6, B12 – usual vitamins present in B complex
• A unit of enzyme activity which converts 1 mol of supplement
substrate per second - function for the nerve
• Has not yet received universal acceptance * Folic Acid, B6, B12 – Deficiency would possibly lead to
anemia
Enzyme Regulation - functions for RBC
1. Feedback control – the concentration of the product
influences the rate of reaction.
2. Allosterism – an interaction takes place at a position other Most Common Disturbances
than the active site but affects the active site, either positively
or negatively. 1. Kwashiorkor – disease resulting from a deficiency of dietary
3. Some enzymes (proenzymes or zymogens) must be protein relative to caloric intake (protein-energy
activated by removing a small portion of the polypeptide malnutrition).
chains.
4. Zymogens are enzymes produced as inactive proteins. a. The disorder occurs most commonly in young
children in developing countries when mothers’
breast milk no longer provides enough protein, and
 other protein-rich foods are no given in sufficient • is referred to as the disintegration of the naturally
quantity. occurring foodstuff into absorbable forms.
b. The number of calories in the diet of corn meal is • It includes the hydrolysis of starch into
sufficient, but corn is deficient in lysine and monosaccharides, proteins to amino acids, and fats
tryptophan. As a result, a child fails to grow, becomes into fatty acids and glycerol
lethargic, and has an enlarged abdomen from
hypoprotein edema due to the inability to properly TWO FACTORS IN DIGESTION
build proteins.
Primary factor
2. Marasmus – results from slow starvation caused by • includes the different enzymes found in the juices of
deficiency not only of protein but also of calories and other the different portions of the digestive tract
nutrients. • These are necessary in the conversion of complex
molecules to simple and absorbable forms
3. Anemia – blood condition involving an abnormal reduction
in the number of RBCs or in their hemoglobin content. Secondary factors
• Cooking
4. Gout – caused by faulty metabolism of uric acid produced • Mastication breaks down the food and increases
in the body by breakdown of proteins. surface area for enzymes to act.
▪ Factors: diet rich in malt liquors, wines, and certain types of • movements of the stomach and intestines or what is
protein and about 95% are men. known as peristalsis.
• absorption from the intestines,
5. Phenylketonuria (PKU) – this is due to the absence of the • autodigestion such as in the ripening of fruits.
enzyme phenylalanine hydrolase which converts
phenylalanine to tyrosine. Chyme – partially digested food with gastric juices
• Phenylalanine is instead converted to phenylpyruvic
acid which impairs normal development of the CHEMICAL BREAKDOWN OF FOOD
child’s brain leading to mental retardation.
A. MOUTH -carbohydrate
6. Albinism – this is due to the absence of tyrosinase, which is Mechanical digestion in the mouth
necessary for the formation of melanin. • Chewing or mastication
• Food manipulated by tongue, ground by teeth, and
7. Alkaptonuria – this is due to the absence of the mixed with saliva
homogentisic acid oxygenase (homogentisic acid → acetate • Forms bolus – masticated food with saliva
and fumarate). Chemical digestion in the mouth
▪ A disturbance of metabolism in which the skin of the face, • hydrolysis of starch by salivary amylase (ptyalin)
the whites of the eyes, and other tissues such as muscle and • takes place in the buccal cavity and to a certain
cartilage become discolored brown. (The urine is also a dark, extent in the fundic end of the stomach
brownish color.) • Starch & glycogen → maltose

8. Tyrosinosis – this is due to the absence of Saliva - lubrication

hydroxyphenylpyruvic acid oxygenase which converts • Colorless slightly viscid, opalescent fluid which is a
hyroxyphenylpyuvic acid to homogentisic acid. mixture of secretions of the three pairs of salivary
a. Infants exhibit diarrhea, vomiting, and a “cabbage-like” glands
odor and fail to thrive. ▪ Parotid gland – section is watery and rich in ptyalin
b. Without treatment, death from liver failure ensues 6-8 ▪ Sublingual gland – secretion is more viscid containing mucin
months. and poorer in ptyalin
c. Treatment: diet low in tyrosine, phenylalanine, and • Average secretion per day is 1,500 ml
methionine. • 99.42 % water
• 0.58 % solid
• 2/3 = org. matter (mucin, ptyalin, urea, glucose, lactic
BIOCHEMISTRY OF DIGESTION
acid…)
• 1/3 = inorg. Salts (Cl-, HCO3- of Na, K, Ca, SO4- and
DIGESTION PO4- )
• pH: 7.0 – 7.3 (active stimulation)
 • 6.4 – 6.9 (resting saliva)
• Function: moisten and reduce the foods into a Composition
consistency suitable for swallowing • 99.4 % water
• 0.6 % solid
Factors influencing the secretion of saliva • organic constituents: mucin, pepsin, & small amount
1. Psychic – thought, smell, sight of lipase
2. Chemical - condiments chemical present with food; food • Inorganic Constituents: HCl, KCl & PO4-
contact with the mouth
3. Mechanical – movement Pepsin
• principal digestive constituent of the gastric juice
Salivary amylase • pepsinogen – activated by HCl; Inactivated at neutral
• ptyalin pH or alkaline pH
• Endoamylase which acts only on the alpha 1,4- • Peptide bonds pepsin di or tripeptide/shorter)
glycosidic linkages • autocatalytic
• Splits starch into the disaccharide maltose • Optimum activity: pH 1.5 – 2.5
• activators: Cl- (most active) & Br -; I- & NO3 • An Endopeptidase that acts on peptide bonds
• Unstable below pH 4 – 5
• Inactivated by pepsin Mucin
• not digested by pepsin
B. STOMACH - protein • Protects the mucous membrane of the stomach
Gastric Digestion • Buffers the HCl
• Mainly concerned with the digestion of proteins thru • Promotes absorption of Vit. B12
the action of the enzyme pepsin and HCl
• Pepsin – initiates protein digestion producing Rennin – milk –curdling enzyme found in the gastric juice of
proteoses, peptones and polypeptides newborn infants
- The gastric juice on infants contain little or no pepsin but
3 Phases in Gastric Digestions high concentration of HCl

1. Psychic phase Inhibitors of Gastric Secretion

a. Stimulation of gastric secretion due to the smell, sight, taste
and thought of food Enterogastrone – produced from the presence of fats in the
b. Gastrin – secreted by G cells in the pyloric region of the intestines which inhibits gastric secretion and motility
stomach, it stimulates the secretion of an acid rich gastric Urogastrone – found in urine: similar to entrogastrone
juice Acids inhibitors
• 0.03 N HCl – slows secretion
2. Gastric Phase • 0.1 N HCl – inhibits parietal cells
a. Initiated by food in the stomach
b. Secretagogue – present in certain food which stimulates Functions of HCl
the secretion of gastrin (hormone from the pyloric mucosa) • Provide suitable pH for protein digestion by pepsin
• Exerts preliminary swelling, denaturing and
3. Intestinal phase hydrolyzing effect on proteins
a. Initiated by digestive products in the upper small intestine • Activates pepsinogen
b. Secretin – a hormone released by the duodenum acting on • Facilitates absorption of iron
the stomach, it stimulates the secretion of gastric juice, • Causes hydrolysis of disaccharides
pancreatic juice, intestinal juice and bile • Stimulates secretion of secretin
• Exerts germicidal action

Gastric Juice Pathological Variation of HCl

• Average secretion per day is 2-3 liters ▪ Achloridia:
• Contributed by three types of cells from the gastric - absence of free HCl
glands - seen in Pernicious anemia
o Parietal cells – secrete HCl (0.17N), pH 0.87 ▪ Achylia gastrica
o Chief cells – secrete pepsin - partial or complete absence of gastric juice
o Mucosal cells – secrete mucin - indicates degeneration of the gastric glands
▪ Hypochloridia: • Endopeptidase acting on peptide linkage involving
- suggestive of chronic gastritis or gastric carcinoma carboxyl group, arginine and lysine
▪ Hyperchloridia: • Protein splitting enzyme and an endopeptidase
- suggestive of peptic ulcer, cholecystitis. • Secreted as trypsinogen - activated trypsin by
enterokinase
Intestinal Digestion • Acts upon peptide linkages
• Splits proteins and products of pepsin digestion into
C. INTESTINES peptides
2. Chymotrypsin
• Endopeptidase acting on peptide bonds involving
Hepatopancreatic ampulla – it phenylalanine, tyrosine and tryptophan
is the connection of bile duct • Activated by trypsin
and pancreatic duct • Powerful milk-curdling effect
o Peptidases
▪ All intestinal enzymes except two
▪ Split peptides into amino acids
3. Carboxypeptidase
• Zinc-containing enzyme
• Exopeptidase attacking the peptide linkage nearest
the free hydroxyl group
4. Pancreatic amylase
• Also known as diastase and amylopepsin
Pancreatic Juice – most alkaline • Rapid hydrolysis of starch
• Secreted by the acinar cells of the pancreas • Converts starch and glycogen into maltose
(500ml/day) 5. Pancreatic Lipase
• Clear, watery solution made up of 98.7% water and • Also known as steapsin
1.3% solids • It exhibits weak lipolytic effect
• It is the most alkaline of the normal body fluids (pH • Action is potentiated by bile acids, calcium and
7.5 – 8.2) due to its bicarbonate content certain amino acids
o Organic constituents (1/3) • It splits fats into monoglycerides, fatty acids and
• Trypsin, chymotrypsin (proteolytic enzymes) - protein glycerol
• Steapsin (lipolytic) – lipid 6. Nucleodepolymerase
• Diastase (amylolytic) - carbohydrate • Ribonucleases and deoxyribonucleases
• Nucleolytic enzymes
• They hydrolyze the corresponding nucleic acid into
o Inorganic constituents (2/3)
mononucleotides
• Sodium
Intestinal Juice (Succus Intericus)
• Potassium
• Calcium • Combined secretion of the intestinal glands at
• Bicarbonate – most dominant different portions: duodenum, jejunum, ileum
• Chlorides • Viscous and turbid fluid due to mucin and
• Phosphates desquamated epithelial cells
• Enterocrinin – hormone secreted by the intestinal
Regulation of Pancreatic Secretion mucosa and stimulates the mucosal glands to
1. Vagal Stimulation increase volume of fluid and the content of enzyme
a. Secretion is rich in enzymes but less volume
b. Occurs during cephalic and gastric secretion Enzymes in Intestinal Juice
1. Carbohydrases
2. Hormonal stimulation a. Maltase
a. Secretin – stimulates secretion of a fluid of high volume b. Lactase
and bicarbonate content c. Sucrose (invertase)
b. Pancreozymin – stimulates enzyme secretion 2. Peptidases
a. Aminopeptidase – exopeptidase, attacks the peptide
Enzymes in the Pancreatic Juice linkage of the N-terminal amino acid containing free amine
1. Trypsin group which requires Mg++ or Mn++
* C -terminal - carboxypeptidase
b. Tripeptidases and Dipeptidases – split tripeptides and
dipeptides into their constituent amino acids which require Bile Pigments
Co++ and Mn++ ▪ From the degradation of hemoglobin
➢ Biliverdin – cause green color of bile
3. Nucleotidases (Nucleophosphatases) – split the ➢ Bilirubin (formed from the reduction of biliverdin) – cause
nucleotides into phosphoric acid nucleosides yellow color of bile

4. Nucleosidases – purine nucleosidase; pyrimidine Chemical Changes in the Large Intestine

nucleosidase
D. LARGE INTESTINES
Bile (fel) While its true that the large intestines produce no digestive enzymes, it is still
• Clear, golden yellow, slightly viscid fluid a part of the digestive system. It functions primarily on the absorption of
water and electrolytes and the elimination of feces. Note however, that there
• secreted by the liver cells
are chemical changes that occur in the large intestines.
• Average secretion of 500 – 700 ml/day
• Stored in the gall bladder where it undergoes Chemical Changes in the large Intestines
concentration • The semi-liquid residue which has escaped digestion
• Gall bladder bile is more concentrated, more viscous and absorption are passed into the large intestines.
and dark yellow-green in color • The presence of intestinal microorganisms
• Cholecystokinin – hormone which stimulates the disintegrates these organic residues into simpler
discharge of bile into the bowel (relaxation of the fragments
sphincter Oddi and Contraction of the gall bladder)
• Cholagogue – substance that stimulates the flow of 1. Fermentation (carbohydrate)
bile • Bacterial degradation of carbohydrates under
• Solid content (1 - 4%) anaerobic conditions
Organic components (3/4) Inorganic
▪ Bile acids ▪ HCO3-
• Products are
▪ Bile pigments ▪ Cl – Chlorine - dominant Organic acids Gases
▪ Bilirubin ▪ Na ▪ Lactic acid ▪ Methane
▪ Cholesterol ▪K ▪ Formic acid ▪ Carbon dioxide
▪ Small amount of ▪ Propionic acid ▪ Hydrogen gas
▪ phospholipid (Lecithin)
▪ Succinic acid
▪ Mucin, Urea, ALP

Liver Bile Gall Bladder Bile 2. Putrefaction (protien)

▪1-4% ▪ Solids: 4 - 17% - Bacterial decomposition of protein under anaerobic
▪ Less viscous ▪ more viscous
▪ Golden yellow ▪ dark yellow-green conditions
▪ pH 7 - 8.5 ▪ pH 5.5 Tryptophan -> Indole + skatole

 Fiber + bile = eliminated 3. Deamination

 Body will form bile using cholesterol - Removal of amine group from simple amino acids to form
short-chain organic acids
Bile acids
1. Cholic acid – 26 – 60% of the total 4. Decarboxylation
2. Chenodeoxycholic acid – 30 – 50% - Removal of carboxyl group forming amines
3. Deoxycholic acid – 5 – 25%
o These bile acids are conjugated with glycine or taurine to Detoxification
form bile salts - Includes all processes by which noxious substances are
rendered less harmful or more easily excreted
Functions of bile
1. Activate steapsin Reactions Involved
2. Aid in absorption of fat and fat-soluble substances by 1. Oxidation
forming water-soluble complex (hydrotropic effect) - One of the most important means of detoxification
3. Enhance digestion of fat (emulsification) - Example:
- lowers surface tension, and disperse in an emulsion which Ethyl alcohol + Oxygen = carbon dioxide + water
enhances digestion of fat
4. Choleretics (stimulate secretion of bile) 2. Reduction – has minor role in detoxification
5. Maintain cholesterol in solution
3. Hydrolysis – some drugs used for therapy are hydrolyzed in
the body
Acetylsalicylic acid = salicylic acid + acetic acid

4. Conjugation
• Process called upon whenever oxidation becomes
ineffective
• Brought about by the combination of the toxic
substances or one of its metabolites with a
compound occurring normally in the kidney
• Occurs chiefly in the liver
• Conjugating agents
o Acetic acid
o Cysteine
o Glucoronic acid
o Glutamine
o Glycine
o Methyl group
o Sulfuric acid
o Thiosulfate
 1. Energy Yielding Nutrients – they serve as primary
source of metabolic fuel needed by a living body and
as means to store and reserve energy in the form of
glycogen
2. Serve as structural components of the living cells -
as carbohydrates combine with proteins, they from
glycoproteins and proteoglycans that are very
important components of the cell membrane
3. Serve as structural framework – for DNA and RNA as
part of nucleotides
4. Mediate Interaction between cells – blood types are
determined by specific membrane bound CHO
5. Building materials – cellulose is found in wood,
cotton, paper
6. Serve as a backbone or precursor substance of some
important molecules mucopolysaccharide

FINALS GENERAL CLASSIFICATION

sdfsdf CARBOHYDRATES Monosaccharides

➢ The simplest carbohydrate – has only one saccharide unit
 Commonly known as sugars
➢ Cannot be broken into smaller CHO molecules by
 They are defined as polyhydroxy aldehydes or
hydrolysis
polyhydroxy ketones or substances that yield these
➢according to location of carboxyl group
compounds when hydrolyzed
Disaccharides
 Aldehyde and ketone derivative of polyhydric alcohol
➢ Contains two monosaccharide units
 Saccharide (Greek word) sugar simple CH2O
(monosaccharide and disaccharide) ➢ It can be hydrolyzed to give two monosaccharide units
 The simplest structural unit of carbohydrate is known
as saccharide Oligosaccharide
 In Latin, Saccharine means sugar ➢ Polymers made up of two to 10 (2-10) monosaccharide
 Excess consumption: obesity, diabetic, tooth decay units

CHARACTERISTICS OF CARBOHYDRATES Polysaccharides

 Hydrates of carbon – so called because the ratio of ➢ Giant polymers made of many monosaccharide units
hydrogen to oxygen is the same as that of water (2:1) ➢ The most complex CHO because they contain more than 10
 The cheapest source of cellular fuel – in the form of saccharide units
ATP
 These are chemically defined as aldehyde and ketone
derivatives of polyhydric alcohols (presence of ACCORDING TO NUMBER OF CARBON ATOMS
several -OH groups) ❖ Trioses – with three carbon atoms
 1 gram of CHO = 4 calories ❖ Tetroses – with four carbon atoms
 Starch is the most abundant plant CHO ❖ Pentoses – with five carbon atoms
 Glycogen is the most abundant storage of animal ❖ Hexoses – with six carbon atoms
CHO ❖ Heptoses – with seven carbon atoms

IMPORTANCE AND FUNCTIONS ACCORDING TO ITS FUNCTIONAL GROUP

❖ The functional group of carbohydrates is the carbonyl ASYMMETRIC CARBON
group (-C=O) ➢ refers to the C atom in the structure of a sugar to which 4
❖ Aldose - polyhydroxy aldehyde different radicals are attached
and the carbonyl group is found at
one of the terminal sides of the
hydrocarbon chain
❖Ketose - polyhydroxy ketone and
the carbonyl group is found in
between 2 hydrocarbon groups ;
R1(CO)R2 OPTICAL ACTIVITY/ MUTAROTATION
➢ the ability of a sugar solution to bend or deflect the plane
of polarized light.
➢ (d or +) DEXTROROTATORY (to the right) clockwise
➢ (l or -) LEVOROTATORY (to the left) counter clockwise
➢ Example • + glucose • - fructose

ENANTIOMERS (MIRROR-IMAGE ISOMERS)

➢ Stereoisomerism/ enantiomerism
➢ Depends on the spatial orientation of the –H and –OH
group attached to the carbon atom adjacent to the terminal
primary alcohol group
➢ the ability to form two sugars which are mirror images to
each other (D- isomer or L-isomer).
➢ The configuration is based on the location of the –OH
linked to the C atom which is the next to the terminal.
➢ D-isomer: -OH is on the RIGHT of the C atom adjacent to
EPIMERS:
the terminal primary alcohol group
➢ two sugars which
➢ L-isomer: -OH is on the LEFT of the C atom adjacent to the
differ only in the
terminal primary alcohol group.
configuration
around a single C ➢carbohydrates are in the D-isomer
atom
MONOSACCHARIDES

➢ Simplest carbohydrates which cannot be broken down into

smaller carbohydrate molecules
1. Trioses (C3H6O3) – glyceraldehyde,
dihydroxyacetone
2. Tetroses (C4H8O4) – erthyrose, erythrulose
3. Pentoses (C5H10O5) – xylose, ribose, deoxyribose,
arabinose, rhamnose
4. Hexoses (C6H12O6) – glucose, galactose, mannose,
fructose
5. Heptoses (C7H14O7) – mannoheptose,
mannoheptulose
NOMENCLATURE OF MONOSACCAHRIDES
1. To give the number of carbon atoms in a monosaccharide
formula, numerical prefixes are used
 -Prefix + ose
o Diose, Triose, Tetrose
2. To denote the functional group of a monosaccharide, the
prefix
 Aldo = for hydroxyaldehydes
 o Glyceraldehyde – aldehydetriose or o Blood concn: 80 – 100 mg/dL
aldotriose
 Keto = for hydroxyketones
o Dihydroxyacetone – ketonetriose or
ketotriose

IMPORTANT MONOSACCHARIDES ➢ D-Galactose

• brain sugar – D-glucose is found in the brain and
1. Diose – a monosaccharide with 2 carbon sugars nervous tissue in the form of glycolipids
 They are the simplest carbohydrates • An aldohexose; Less than half as sweet as glucose
 Example: Glycoaldehyde • Not a natural sugar
2. Triose – a monosaccharide with three carbon atoms • Has the fastest rate of absorption in the intestines
 Glyceraldehyde ➢ D-Fructose (levulose/fruit sugar)
o Produced from the breakdown of larger • Sweetest sugar
monosaccharides • A natural ketohexose; occurs in honey
o D-glyceraldehyde with D-glyceraldehyde – 3 • Serves as a source of energy for the sperm cells
– phosphate is an intermediate in the • Liver can convert fructose to glucose
metabolic pathway of glycolysis (conversion
of glucose to lactic acid)
3. Tetroses – carbohydrates containing 4 carbon atoms
Examples
• Erythrose – aldehyde tetrose/aldotetrose ➢ Mannose
• Erythrulose – ketone tetrose/ketotetrose • Bitter taste
• Threose – aldehyde tetrose/aldotetrose • Not found free in nature but is widely distributed in
4. Pentose – monosaccharides with 5 carbon atoms, the most the form of polysaccharide.
widely distributed sugars in the living systems • D-Mannose is the 2-epimer of glucose
➢ Ribose
• Component of ribonucleic acid (RNA), RNA sugar
• RNA – is a polymeric compound that plays a major DISACCHARIDES
role in the synthesis of protein molecules • Composed of two saccharide groups
➢ Deoxyribose • Formed when two monosaccharide molecules
• DNA sugar combine by splitting out a molecule of water
• DNA – is a compound which transmits genetic • The glycosidic linkage that joins the two sugars
information from parent to offspring by directing the always involves the hemiacetal –OH group of one
synthesis of protein molecules sugar and one of the OH groups of the other
➢ Xylose monosaccharide
• Found in nuts
• Also known as sugar alcohol IMPORTANT DISACCHARIDES
• It is a sugar that is not normally metabolized
• It is used to detect CHO malabsorption 1. Maltose
• Xylose excretion test • Malt sugar
➢ Arabinose • Found in starch and glycogen
• Found in nuts • The malt produced includes malt starch and enzymes
• Known as gum sugar that are able to convert malt starch into maltose,
5. Hexoses – monosaccharide with 6 carbon atoms which is then fermented to produce alcohol
➢ The aldohexoses, ketohexoses and aldopentoses will • Linkage: alpha - 1,4
receive special attention since they include the most • Found in combined form as starch and is one of the
important monosaccharides in living systems intermediate products in the digestion of starch
➢ Glucose (grape sugar/blood sugar/plasma • Derived from “malting” (soaking, germinating and
sugar/dextrose) drying of grains such as barley)
• Common ; circulating CHO 3. Lactose
• Most common source of cellular ATP and from which • Also known as milk sugar
most complex carbohydrates are made form • Least soluble and least sweet disaccharide
• Natural sugar mostly in the D form • Made by combining B-D-Galactose and D-glucose
 • Linkage: Beta-1,4 • Upon hydrolysis, yield simple sugars and sugar
• In the body, it is broken down by the action of the derivatives
enzyme known as LACTASE • Polysaccharides with large MW are antigenic
• Deficiency of the enzyme leads to inability to absorb
lactose and the condition called LACTASE CLASSIFICATION
DEFFICIENCY SYNDROME or LACTOSE INTOLERANCE 1. Storage polysaccharide: Starch and Glycogen
o This condition is controlled by eliminating all 2. Structural polysaccharide: Cellulose and Chitin
3. Acidic polysaccharide: Heparin and Hyaluronic Acid
dietary sources of lactose (e.g. dairy
products, some medications)
TYPES:
• Normal lactose metabolism (small intestine) HOMOPOLYSACCHARIDES - carbohydrates with similar,
• absence of lactase (happens in colon) repeating units
o enzyme lactase will be replace by bacteria  Glucosans - upon hydrolysis, yield only glucose units
w/c will be present causing bloating or (Eg. starch, glycogen, cellulose)
diarrhea  Fructosans - polymerized fructose units
Example: Inulin
4. Sucrose
• Also known as table sugar (raffinose, invertose, 1. Starch
invert sugar, saccharide)  It is a glucosan and can be hydrolyzed into several
• Non reducing in nature glucose units by dilute inorganic acids or by mixing a
• Made by combining alpha-D-glucose and beta-D- solution of diastase
fructose  AMYLOSE (98%) - linear structure; a-1,4 linkages
 AMYLOPECTIN (2%) - highly branched chain; a-1,6
• Linkage: alpha,beta - linkage
linkage
• Considered as a non-reducing sugar, a sugar which
• Starch hydrolysis
does not react with Tollen’s or Benedict’s reagent
 Hydrolysis of starch either by the action of amylolytic
• Main sources: sugar and sugar beets enzyme or by acid gives rise to split fragments with
• When sucrose undergoes hydrolysis, it produces an simultaneous production of maltose
equimolar mixture of glucose and fructose (sweeter)  In the presence of maltase, maltose is converted to
called INVERT SUGAR through the action of the glucose. In acid, however, the final product is glucose
enzyme SUCRASE or INVERTASE
Starch amylase maltose glucose
Artificial sweetener – substance that is sweeter than sugar
but without calories Starch acid glucose
• Aspartame – commonly used
• Acesulfame K 2. Glycogen
• Saccharin – soft drinks  Storage form of carbohydrates in animals
o Oldest and it is banned from the market  Glucose polymer stored in the liver
 A-1,6 linkage occurs about 8-12 glucose units (24-30
because if causes gallbladder
units for amylopectin
• Sucralose
 Glycogenolysis -> glucose

2. Cellobiose 3. Cellulose
• Composed of 2 glucose molecules ; Linkage: beta –  Most abundant organic substance found in nature
1,4  Insoluble carbohydrate which is the chief structural
• Produced from the breakdown of the polysaccharide component of plants and wood.
cellulose Fiber consumption
• Mammalian digestive tracts do not secrete enzymes  Necessary to lower blood cholesterol
that can break the beta – 1,4 linkages between 2  Prevent constipation
glucose molecules  Provide bulk
POLYSACCHARIDES 5. Dextrin
 Intermediary products of starch hydrolysis
Important properties of polysaccharides  Amorphous, white powder
• White, tasteless, amorphous compounds  Dextrin amylase -> maltose
• X-ray analysis: crystalline  Dextrin acid -> glucose
• No reducing property; do not form osazone crystals
• High MW; mostly are insoluble TYPES:
• Non-fermentable by yeast
HETEROPOLYSACCHARIDES - carbohydrates which upon • Pentoses furfural
hydrolysis, yield sugar and sugar derivatives
Examples: CHEMICAL PROPERTIES OF CARBOHYDRATE
Hyaluronic acid -yields glucoronic acid, glucosamine and
acetic acid 1. Reducing Power
Chondroitin sulfate • all mono and disaccharides containing the potentially
free aldehyde or ketone group possess reducing
Hyaluronic acid properties;
Function: • reduce alkaline metals and are transformed into organic
 Lubricant acids
 Cementing substance which allows passage of
metabolites but not of the infective organisms A. Benedict's Test
 It is fragmented by hyaluronidase (spreading factor), Reagent: CuSO, in NaOH and Na Citrate
an enzyme found in bacteria, sperm and in the Positive result: Reddish brown to red ppt
poisonous secretions of reptiles and other animals
B. Fehling's Test
Heparin Reagent: CuSO4 in NaOH and Na-tartrate
 Generated by certain types of cells lining arterial Positive result: Reddish brown to red ppt
blood vessels and by the lung tissues
 Powerful inhibitor of blood clotting thus preventing C. Nylander's test
intravascular coagulation Reagent: Bismuth subnitrate
 In practice, it is used to prevent clotting of blood Positive Result: Black colored solution
specimens (use of leech)
D. Barfoed's test
Reagent: cupric
acetate in weak acetic
acid
PHYSICAL PROPERTIES OF CARBOHYDRATES
Positive result: Red
ppt
Use: To differentiate monosaccharides from disaccharides
1. Mono and disaccharides - white and crystalline
• Starches - amorphous powder
E. Tollen's Test
• Cellulose - fibrous
Tollen's reagent:
2. Solubility (in ordinary solvents) - inversely proportional to
• 5% silver nitrate,
the complexity of their structures
10% Sodium
hydroxide
mono and disaccharides - more soluble in water higher CHO
• Dilute Ammonium
(e.g. starch) - insoluble; form colloidal solutions
hydroxide(7ml NH3 +
Cellulose - practically insoluble
100ml H20)
+ result: Formation of silver mirror
3. Mono and disaccharides - sweet
Use: To differentiate aldehydes from ketones
Starches and Cellulose - tasteless

Relative sweetness of sugars:

o Cane sugar (sucrose) - standard of sweetness CHEMICAL PROPERTIES OF MONO & DISACCHARIDES
• Grape sugar (Fructose) - sweetest A. Bial's Orcinol-HCI test
• Milk sugar (lactose) - least sweet Reagent: Bial's reagent: Orcinol in 95% Ethanol,
10% FeCI3.6H20, 2, ml Orcinol-HCI (+ 1 mi sugar solution)
Positive Result: green solution to deep blue green product
Use: To distinguish a pentose from a hexose
B. Tauber's Benzidine Test
Reagent: 4% solution of benzedine in glacial acetic acid
CHEMICAL PROPERTIES OF MONO &
(tauber's reagent) 1 mi Benzidine (+ 2 drops of sugar solution)
DISACCHARIDES
Positive result: Violet color
Use: test for the presence of pentoses
Action of Non-Oxidizing Agents
*Higher conn: CHEMICAL PROPERTIES OF CARBOHYDRATE

• Mono dehydrated furfural derivatives 2. Osazone formation

• Hexoses Hydroxymethylfurfural
 • reducing sugars form characteristic osazone crystals
when heated with an excess of phenylhydrazine Fermentation of Sugars
(CH,NHNH,)
• attributed to the presence of aldehyde or ketone • CHO enzymes alcohol or acid
group in their molecules • This process in utilized in the manufacture of
• Due to this property, sugars can be identified from a beverages and other industrial products
mixed sample
• Glucose, mannose and fructose have the same Zymase – enzyme in the yeast which produces fragmentation
configuration and thus yield the same crystals which of the sugar molecule
makes identification difficult

Action of AlkaliDIGESTION
on CHO AND ABSORPTION DIGESTION AND ABSORPTION
Moore's test: a solution containing free aldehyde or ketose
group is boiled with strong NaOH -> brown color
 For complex carbohydrates to be of value, these
(condensation)
should undergo digestion
4. Action of Acids 60% of food ingested is complex carbohydrates
 Starch and glycogen – fragmented into simple
Molisch test monosaccharides
Reagent: Alpha-naphthol and 95% ethyl alcohol and Conc.  Cellulose and pentosans – no digestive enzymes for
H,SO, humans
Positive Result: Violet ring at the junction of the two liquids  Cellulose – cellulase – bacterial enzyme that acts on
Use: General test for carbohydrates cellulose, however, nutritive value is insignificant
 Pentosans – acted upon by bacteria to produce
Anthrone test organic acids, alcohols and carbon dioxide
Reagent: Anthrone (Keto form of 9-hydroxyanthracene or 10-
hydroanthracene-g-one) & Conc.H2S04
Positive Result: Blue or green color Dietary carbohydrates
Use: for rapid detection of carbohydrates in samples like body  Starch
fluids and can be used for cellulose assays  Sucrose
 Cellulose
Seliwanoff's Test  Lactose
Reagent: Resorcinol and HCI  Glycogen
Positive Result: red color (specific for ketoses)  Pentosan
Use: used to differentiate aldoses from ketoses
Starch – the most common dietary form of carbohydrate
Tollen's Phloroglucinol test
Reagent: Phloroglucinol - Composed of:
Positive Result: Red color (for galactose)  Amylose – linear pattern of glucose linked by α-1,4
glycosidic bonds
 Amylopectin – branched polymer; glucose linked by α-1,4
CHEMICAL PROPERTIES OF MONO & DISACCHARIDES glycosidic bonds with branching via α-1,6 - linkages
Oxidation of Sugars
• Aldonic acids: oxidation
of the aldehyde group of
the aldose sugar to a
carboxyl group
• Uronic acids: DISGESTION
oxidation of the
primary alcohol to
MOUTH/BUCCAL CAVITY
a carboxyl
 First area where carbohydrates undergo digestion
group
 Contains Ptyalin or Salivary Amylase
 Chemical action
Ester formation  Mechanical action
• (-OH)... (+) acid -> Ester
• the presence of the primary alcohol group (-CH2OH) 2 classes of amylases
in the sugar molecule make it reactive with an acid
Alpha – amylases (alpha-1,4 glucan 4 glucanohydrolase) (LI) from bulk or roughage swells in water
 Found in pancreatic and salivary juices
 Saccharogenic amylase
 Found in human GIT Peristalsis and bowel evacuation
 Split/ break alpha 1,4 glycosidic bonds (except those
of maltose) in random fashion

Beta-amylases (alpha-1,4 glucan maltohydrolase)

 E.g barley malt
 Dextrinogenic amylase
 Breaks β-1,4 glycosidic linkage
 Not found in human GIT
 Equivalent enzyme is CELLULASE ; found among
ruminants or grass-grazing animals with large cecum
(e.g. cows, carabaos, horses, goats)
 Effects the successive removal of disaccharides
(maltose units) from the non-reducing ends
o The enzyme cannot hydrolyze the alpha-1,6
bonds and the reaction stops at this point.
o The fragment which remains is called
DEXTRIN or LIMIT DEXTRIN

STOMACH
 wave like contraction of muscle fibers
 Little digestion of polysaccharide https://www.slideshare.net/soniherat/digestion-and-absorption-of-
o Gastric juice has no carbohydrate-splitting carbohydrate
enzyme
o Salivary amylase is inactivated by pepsin ABSORPTION
o Fructosans are broken down by HCl  Pores of the mucosa through which diffusion occurs
are impermeable to water soluble solutes with MW >
SMALL INTESTINES than 100.
 Digestion of polysaccharides & disaccharides is  Simple Diffusion: pentose
complete  Facilitated Diffusion: involves a carrier protein or
 Peristalsis continue lipoprotein (fructose and mannose)
 Complete chemical digestion of carbohydrate  Active Transport: glucose and galactose
o Pancreatic secretion: amylase o carrier transport is present in the brush
o Intestinal secretion: disaccharides border of the epithelial cell.
 CHO absorbed in the jejunum in the form of o The carrier has a receptor site for both
monosaccharides glucose and sodium.
 pancreatic amylase and disaccharidases hydrolyze o It will not transport glucose to the inside of
CHO into monosaccharides the cell if the receptor sites for both glucose
 Undigestible CHO due to β-1,4 glycosidic bonds and sodium ion are not simultaneously
 Examples: high-fiber fruits and vegetables which filled.
contain Cellulose, hemicelluloses and Pectin
 In the L.I., these form bulk or roughage which swells
with water, promoting peristalsis and easier
evacuation of stool.
o The energy to cause the movement of the
Indigestible carbohydrate: carrier from the exterior of the membrane
to the interior is derived from the difference
Cellulose, Hemicellulose, and pectin in sodium concentration between the
outside and the inside
o As sodium diffuses to the inside of the cell,
it drags the carrier and glucose along with
 it, thus providing the energy for the  Serves to capture the monosaccharide in the cells.
transport of glucose.
Blood Glucose
Relative rate of transport of monosaccharides (glucose as  Mostly in the free form, a-d-glucose with small
standard) amount of phosphate ester and only trace of other
- Galactose 110% hexoses
- Glucose 100% o NV: 80-100 mg / 100ml of blood
- Fructose 43% o 70-100 mg before breakfast
- Mannose 19% o 130-160 mg postprandial
- Pentoses 9% • It is the major energy source that crosses the blood
brain barrier
VEINS of the GIT  If the level of glucose falls to 25 %, the individual
1. Superior mesenteric veins becomes stuporous, followed by coma in 10 minutes
2. Splenic veins which becomes irreversible after 30 minutes
3. Inferior mesenteric veins  Very efficient physiological and hormonal
mechanisms keep the blood level at 60 % even in
PORTAL VEIN Liver prolonged starvation

* The absorbed monosaccharides are brought to the 3 big METABOLIC PATHWAYS:

veins of the GIT. 1 fuses with 2, 2 fuses with 3 to form a big  Glucogenesis: conversion of non-glucose hexoses
portal vein to transport monosaccharides into the LIVER into glucose
 Glycogenesis: synthesis of glycogen from available
Carbohydrate malabsorption or Disaccharide Intolerance glucose units
 Glycogenolysis: breakdown of glycogen to yield
Hereditary deficiencies of enzymes glucose units
(e.g. sucrose, maltose or lactose)  Gluconeogenesis: conversion of non- CHO sources
(e.g. amino acids) into carbohydrate substrates
Bacterial decomposition Involves removal and transfer of amino groups
(transdeamination)
Organic acids and gases
Factors that lower blood glucose levels
1. Glycogenesis – transformation of glucose into glycogen (in
the muscle and other tissues)
Flatulence and diarrhea 2. Glycolysis – utilization of glucose for heat and energy
3. Lipogenesis – conversion of glucose to fats
Reducing the offending disaccharide from the diet is needed 4. Formation of certain amino acids
to control the condition. 5. Glucosuria – excretion of glucose in the urine

Hormone that lowers blood glucose levels

1. Insulin
 Foster glycogenesis and lipogenesis
 Hormone secreted by B-cells of islets of Langerhans
in pancreas
o - Produces hypoglycemic effect by o
CARBOHYDRATE METABOLISM Increasing glycogenesis
o Decreasing gluconeogenesis
o Increasing glucose utilization by tissues
Phosphorylation
o Promoting lipogenesis
 Monosaccharides combine with a phosphate radical
 Facilitates entrance of glucose in the cell where it is
= Phosphorylated sugar (will NOT diffuse back to the
immediately phosphorylated to be converted to energy
small intestine.)
to undergo glycolysis
Glucose + APT Glucokinase G-6-PO4
 Deficient insulin diminishes entrance of glucose in the
hexokinase
cell, thus less phosphorylation
 Glucose remains in the blood producing hyperglycemia
 -f its concentration exceeds the renal threshold, it is  Conversion of glyceraldehyde-3-PO4 into lactic acid,
excreted in the urine with energy yield conserved as ATP
 This is known clinically as diabetes mellitus
EMBDEN-MEYERHOF PATHWAY (EMP)
Factors that increase blood glucose level
1. Glycogenolysis 1. Phosphorylation
- Conversion of liver glycogen into blood glucose
2. Gluconeogenesis
- Synthesis of blood glucose from non-CHO sources
3. glucose from other substances (lactic acid, amino acid etc.)

Hormones that increase blood Glucose

2. Isomerization
A. Glucagon – from the a-cells of the islets of Langerhans
B. Epinephrine
C. Growth hormones complex
(both adrenal cortical hormones)
D. ACTH

Fate of Glucose 3. Phosphorylation

1. Blood glucose (also called physiologic sugar)
2. Glycogen - stored glucose
3. Alpha-keto acids – part of non-essential amino acids
4. Constituent of body structures
5. Lipogenesis – produce adipose fat (from glycerol)
6. Pyruvate – key metabolite in the Kreb’s cycle
4. aldose reaction
2 Major Pathways: (first stage ended)
Embden-Meyerhof pathway (EMP)
 Also known as the glycolytic pathway
 Glucose is broken down to pyruvic and lactic acid in
the absence of oxygen (anaerobic)

Kreb’s Cycle
5. Oxidative steps
 Acetyl CoA (EMP)is split to carbon dioxide, water and (OXIDATION AND
energy in ATP PHOSPHORYLATIO
 This is the final common pathway for glucose, fatty N)
acids and certain amino acids
 90% of energy is derived from this pathway

Glycolysis 6. Phosphorylation
 Hydrolysis of glucose; major pathway for the
utilization of glucose
 Anaerobic glycolysis (cytoplasm)
 Aerobic glycolysis (mitochondria)
Impt: Production of Adenosine triphosphate (ATP)
7. Isomerization
2 Stages
 Phosphorylation and cleavage of glucose
End product: glyceraldehyde-3-PO4
 FATE OF PYRUVATE
 Reconverted to glucose-6-phosphate
 Combine with NH3 to form alanine
 May combine with CO2 to form oxaloacetic acid
 May be oxidatively decarboxylated and combine with
CoA to form acetyl CoA
8. Dehydration
Inhibition of Anaderobic Glycolysis by Oxygen (Pasteur
Effect)
 Rate of glycolysis was based on the disappearance of
glucose and accumulation of lactic acid
 The rate of glycolysis is slowed in the presence of
Oxygen
 Oxygen: lactic acid O2 and H20
9.Phosphorylation  Energy released: utilized to resynthesize glucose
from remaining lactic acid
 Net effect
o Decrease in the total consumption of
glucose
o Less accumulation of lactic acid

Aerobic Respiration
10.  process where the pyruvate produced in glycolysis
undergoes further breakdown.
 requires oxygen and yields much more energy than
glycolysis.
Two processes:
Krebs cycle
 also known as the citric acid cycle, or the Krebs cycle,
after Hans Adolf Krebs who identified the cycle.
 a series of chemical reactions of central importance
in all living cells that use oxygen as part of cellular
respiration.
 part of a metabolic pathway involved in the chemical
conversion of carbohydrates, fats and proteins into
carbon dioxide and water to generate a form of
usable energy.
Electron Transport Chain and Oxidative Phosphorylation
 produces ATP through chemiosmotic
phosphorylation.

INTERCONVERSION BETWEEN MONOSACCHARIDES IN THE

LIVER

 Liver cells contain all appropriate enzymes needed to

promote interconversions between the
monosaccharides
 Most human tissues cannot utilize galactose and
fructose
o Galactose and fructose must be converted
by the liver cells into glucose which is then
transported by the blood to the other cells
 galactokinase and galactose-1-phosphate uridyl
transferase
• Treatment: elimination
of milk products as the
source of lactose
• Some capacity to
metabolize ingested
galactose may develop
later in the life of a
galactosemic person by
the development of the
enzyme UDP Galactose
phosphorylase
FRUCTOSE METABOLISM
• Liver, Kidneys and intestine and adipose tissue can
utilize the fructose as a major source of energy
• Fructokinase – phosphorylates fructose to fructose-1
Phospate
• Hexokinase – phosphorylates fructose to fructose-6-
Phospate, this enzyme has much higher affinity for
glucose than fructose, thus the relative abundance
of glucose in the liver competitively inhibits the
phosphorylation of fructose
• Aldolase – utilizes fructose-1,6 biphosphate as
substrate

CLINICAL SIGNIFICANCE OF FRUCTOSE

FRUCTOSURIA
• A benign disorder caused by the lack of
fructokinase
• It is asymptomatic
• Harmless and may go undiagnosed
• Affected individuals spill fructose into their urine
which might be misinterpreted as glucosuria,
because both yield a positive reducing-sugar test

FRUCTOSE INTOLERANCE GLYCOGENESIS

• lack of aldolase (F-1,6 biPO4 cleavage) • Liver, muscle cells: main storage (All cells of the body
• Char. by hypoglycemia and vomiting following are capable of storing at least some glycogen)
sucrose or fructose intake • Is the metabolic pathway by which glycogen is
• Hypoglycemia: Fructose-1-phosphate inhibits synthesized from glucose 6-phosphate
glycogenolysis and gluconeogenesis • glycogen storage in normal tissues:
• Prolonged intake of fructose by infants with this o 300-320 grams/day
defect leads to vomiting, poor feeding, jaundice o Glucose FAT
and eventually hepatic failure and death (no storage limit)

GALACTOSE METABOLISM 2 Forms of glycogen store:

 free glycogen- one that can be readily released
• Galactose is obtained from milk sugar, lactose  fixed glycogen- one that can be released slowly
• The most important organs that can metabolize
galactose are the liver and erythrocytes GLYCOGENOLYSIS
• Galactosemia, an increased level of serum galactose,  ls the metabolic pathway by which glucose 6
is a major symptom of two enzyme defects, phosphate is produced from glycogen
 Clinical Significance
Hypoglycemia:
release of glucagon and Metabolic Pathways:
epinephrine  Gluconeogenesis:
 is the metabolic pathway by which glucose is
Activate phosphorylase synthesized from noncarbohydrate materials.
 Alanine + a-ketoglutarate -> pyruvate + glutamate
Initiate glycogenolysis  Aspartate + a-ketoglutarate -> oxaloacetate +
glutamate
 The non-carbohydrate starting material for
gluconeogenesis are lactate (from hardworking
Glycogen Storage Diseases muscles and RBC), glycerol (from TAG hydrolysis) and
 Genetically linked metabolic disorders that involve certain AA (from dietary protein hydrolysis or muscle
enzymes regulating glycogen metabolism protein during starvation)
 Symptoms vary & may include muscle cramps and Gluconeogenesis vs Glycolysis:
wasting, enlarged liver, and low BSL. Gluconeogenesis Glycolysis
 Accumulation of abnormal metabolic byproducts can Pyruvate to glucose glucose to pyruvate
damage the kidneys and other organs. 12 compounds 11 compounds

Туре Enzyme Deficiency Clinical

Symptoms
VON GIERKE'S Glucose-6- severe
phosphatase hepatomegaly, and
hypoglycemia,
lactic acidosis,
hyperlipidemia,
failure to thrive
POMPE'S Alpha-1,4- Infant-
glucosidase cardiomegaly,
muscle, early death
Adult-muscle
weakness
CORI'S Amylo-1,6- Hepatomegaly,
glucosidase muscle weakness
(debrancher) and hypoglycemia
ANDERSEN'S Alpha-1,4-glucan, 6- Hepatomegaly,
glucosyl-transferase cirrhosis, failure to
(brancher) thrive, early death

McARDLE'S Muscle Muscle cramps

phosphorylase after exercise, Hormones that regulate blood sugar level
myoglobinuria in Hormone Cell/ organ Function/ use/
some patients that produces role
HER'S Hepatic Hepatomegaly, Insulin Beta-cells Entry of glucose
phosphorylase mild clinical course (liver, muscle,
TARUI'S Muscle Muscle cramps adipose tissue)
phosphofructokinase after exercise, Glucagon Alpha cells Glycogenolysis;
myoglobinuria in gluconeogenesis
some patients Delta cells It inhibits
Somatostatin
VII Adenyl kinase Spasticity, secretion of insulin
decerebration, high and glucagon also
urinary inhibits the release
catecholamine, of GH
death in infancy Growth hormone / Anterior antagonist to
IX Hepatic Hepatomegaly,
Somatotrophic pituitary insulin; it
phosphorylase b increase stimulates lipolysis
kinase liver glycogen hormone
(gluconeogenesis)
concentrations Stimulates
Thyroxine/Tetraiodo-
X Cyclic AMP- Hepatomegaly only glycogenolysis and
thyronine
dependent kinase the rate of gastric
 emptying and  primarily designed to
intestinal generate R5P
absorption of
 convert dietary 5
glucose
Cortisol and chromaffin cells Stimulates carbon sugars into
Corticosteroids - adrenal cortex gluconeogenesis both 6 (fructose-6-
Antagonist to phosphate) and 3
insulin (glyceraldehyde-3-
Epinephrine and chromaffin promotes both
phosphate) carbon
Norepinephrine Cells of the liver and skeletal
adrenal glycogenolysis sugars which can then be utilized by the pathways of
(catecholamines)
medulla physical or glycolysis.
emotional stress
cause increase Ways by which PPP meets cellular needs
production of
 When ATP demand is high, the pathway continues to
epinephrine and
an immediate its end products, which enter glycolysis.
production of  When NADPH demand is high, intermediates are
glucose for energy recycled to G6P and further NADPH is produced.
Human Placental with anti-insulin  When R5P demand is high,
Lactogen activity gestational
for NA and coenzyme
(hPL)/Human diabetes
production, most of the
Chorionic non-oxidative stage is
Somatomammotropin
nonfunctional, leaving R5P
ACTH anterior with anti-insulin
pituitary activity as a major product
(Adrenocorticotropic
hormone)
Somatomedins Liver With insulin-like NADPH
activity  Nicotinamide adenine dinucleotide phosphate
 Produced mainly in the Pentose-phosphate pathway.
Pentose Phosphate Pathway  provides the reducing equivalents for biosynthetic
 primarily an anabolic pathway that utilizes the 6 reactions and for oxidation-reduction involved in
carbons of glucose to generate 5 carbon sugars and protection against the toxicity of ROS (Reactive
reducing equivalents. Oxygen Species).
 oxidize glucose and under certain conditions can  used for anabolic pathways, such as fatty acid
completely oxidize glucose to CO2 and water. synthesis, cholesterol synthesis and fatty acid chain
 Consists of 2 irreversible oxidative reactions followed elongation.’
by a series of reversible sugar-phosphate
interconversions
 No ATP is directly consumed or produced in the
cycle.
 Provides a major portion of the body's
 NADPH which functions as a biochemical reductant Entner-Doudoroff Pathway
 Produces ribose-5-phosphate required for the  series of reactions
biosynthesis of nucleotides that catabolize
 ls the metabolic pathway by which glucose is used to glucose to
produce NADPH, ribose 5-phosphate and numerous pyruvate.
other sugar phosphates.  can occur only in
prokaryotes.
The oxidation steps  Uses 6-
 occur at the beginning of the pathway phosphogluconate
 the reactions that generate NADPH dehydrase and 2-
 The reactions catalyzed by glucose 6-phosphate keto-3-
dehydrogenase and 6-phosphogluconate deoxyglucosephophate aldolase to create pyruvates
dehydrogenase generate one mole of NADPH each from glucose.
for every mole of glucose-6-phosphate (G6P) that  has a net yield of 1 ATP for every glucose molecule
enters the PPP processed, as well as I NADH and 1 NADPH.
Non-oxidative reactions
Tricarboxylic acid cycle (TCA) 1. Condensation
 also known as the citric acid cycle, or the Krebs
cycle, after Hans Adolf Krebs who identified the
cycle.
 a series of chemical reactions of central importance
in all living cells that use oxygen as part of cellular
respiration. 2. Isomerization
 Part of a metabolic pathway involved in the chemical
conversion of carbohydrates, fats and proteins into
carbon dioxide and water to generate a form of
usable energy.

Tricarboxylic Acid Cycle/CAC/Kreb's cycle

3. Oxidative
 reduced NAD (NADH)
Decarboxylation
 reduced Flavin Adenine
 Dinucleotide (FADH2)
 Hydrogen Ion (H+)
 Guanosine Triphosphate (GTP)
 Electron Acceptors: NAD, FAD 4. Oxidative
a. acetyl group of Acetyl CoA Decarboxylation
b. reduced NAD (NADH)
c. Reduced Flavin Adenine Dinucleotide
(FADH2)
d. Hydrogen lon (H+)
e. Guanosine Triphosphate (GTP) 5. Substrate-Level
Phosphorylation
Oxidative decarboxylation of pyruvate
 achieved by removing a CO2 molecule from pyruvate
and then removing an electron to reduce an NAD+
into NADH
 An enzyme called coenzyme A is combined with the
remaining acetyl to make acetyl CoA
6. Dehydrogenation

7. Hydration

Kreb’s cycle: Individual reactions

 8.Dehydrogenation ELECTRON TRANSPORT CHAIN
4 Protein Complexes: tightly bound to the membrane:
Complex I : NADH-coenzyme Q reductase
Complex II: Succinate-coenzyme Q reductase
Complex III: Coenzyme Q-cytochrome c reductase
Complex IV : Cytochrome c
oxidase
Coenzyme Q/Ubiquinone &
cytochrome c: not tightly
associated; serve as mobile -
carriers that shuttle e-
between the 4 complexes

ELECTRON TRANSPORT CHAIN

(Respiratory Chain)
 The cytochromes and the Fe-S protein centers are
one-electron carriers.
The Electron Transport on Chain and Oxidative  NADH, FADH2 and Q are two-electron carriers

OXIDATIVE PHOSPHORYLATION SOURCES of ELECTRON

 process by which the energy stored in NADH and NADH is derived from NAD+-linked
FADH, is used to produce ATP.  dehydrogenases, including:
A. Oxidation step: electron transport chain  Isocitrate, a-ketoglutarate, and malate
NADH + H+ + ½ NAD+ + H2O dehydrogenases of the TCA cycle
FADH2 + ½ O2 FAD + H2O  Pyruvate dehydrogenase
B. Phosphorylation step  L-3-Hydroxyacyl Co dehydrogenase of fatty acid
ADP + PI ATP oxidation
 Miscellaneous NAD+-linked dehydrogenase
ELECTRON TRANSPORT CHAIN FADH2 is derived from FAD-linked dehydrogenases, including:
 series of highly organized oxidation-reduction  Succinate dehydrogenase of the TCA cycle
enzymes  FAD-linked dehydrogenase of the a-
 COMMON pathway: substrates oxidized by enzymes glycerophosphate shuttle
that use NAD or FAD+ as electron acceptor cofactors  Acyl CoA dehydrogenase of fatty acid oxidation
 Miscellaneous FAD-linked dehydrogenases
The Mitochondrial Structure
 Outer membrane – permeable to most small OXIDATIVE PHOSPHORYLATION
molecules  process whereby the free energy that is released
 Intermembrane space – presents no barrier to when electrons are transferred along the electron
metabolites transport chain is coupled to the formation of ATP
 Inner membrane – highly selective; provides from ADP and Pi (chemiosmotic phosphorylation)
transport systems for the following substances:  the main source of energy in aerobic cells
ATP, ADP & Pi  In damaged mitochondria: respiration may occur w/o
Pyruvate, succinate, α-ketoglutarate, malate & oxidative phosphorylation
citrate  free energy may still be released as the electrons is
Cytidine and GTP not trapped as ATP, instead as heat.
 Note: The enzymes of the ETC & oxidative  During electron transport, energy released is used to
phosphorylation, including Succinate dehydrogenase are transport H+ across the inner mitochondrial
found in the inner mitochondrial membrane membrane to create an electrochemical gradient
 Matrix – contains the enzymes of the Kreb’s cycle (except  Energy released by flow of H+ down its gradient is
Succinate dehydrogenase), enzymes of β-oxidation of used for ATP synthesis
fatty acids and other miscellaneous enzyme systems  ATP synthase: H+ channel that couples energy from
H+ flow with ATP synthesis
 Proteins
ATP from Glycolysis  organic compounds of high molecular weight made
up of alpha-amino acids joined by means of peptide
Reaction pathway ATP for One Glucose linkage.
ATP from Glycolysis  fundamental constituent of the protoplasm of the
Activation of Glucose cells. Greek “proteios” which means “of first
importance” or “to take first place.”
 supply the body not only with heat and energy, but
-2 ATP also provide materials for building and repair.
Oxidation of 2 NADH (as 4 ATP  They are the “working molecules” which perform
FADH2) operational functions in living systems (e.g. enzymes,
antibodies, hormones, etc.) and composed of amino
acids as building blocks

Amino Acids: The Building Blocks of Proteins

Direct ADP Phosphorylation 4 ATP
(two triose) Amino acid
 organic compound that contains both an amino (-
NH2) group and a carboxyl (-COOH) group.
 AA in proteins are always the α-amino acids.
 The different components of the amino acid
structure have corresponding functions.
C (alpha carbon)
 is tetrahedral, chiral, asymmetric and covalently
linked to both an amino group and a carboxyl side
Summary:
chain.
C6H1206 2 pyruvate + 2H 2 0 + 6 ATP glucose
 Bonded to it is a H atom and a variable R group.
R side chain
 varies and give the amino acid its characteristics.
 The nature of this side chain distinguishes a-amino
acids from each other.
 Side chains vary in size, shape, charge, acidity,
functional groups present, hydrogen-bonding ability,
and chemical reactivity.
NH2 or amino group exists as –NH3+ in neutral solutions.
COOH or the carboxyl group exist as –COO- in neutral
solution.

CLASSIFICATION OF AMINO ACIDS

1. Non-polar amino acids
Hydrophobic amino acids
 When incorporated into a protein, they are not
attracted to water molecules.
 They are generally found in the interior of proteins,
where there is limited contact with water.
AMINO ACIDS AND POLYPEPTIDES
 Include all those with alkyl side chain R groups
o Alanine
 o Valine  Found only in a light-driven proton-pumping protein
o Leucine call bacteriorhodopsin
o Isoleucine o Pyroglutamic acid
 Cyclic structure
o proline
 sulfur containing amino acids
 cysteine and methionine
 Aromatic amino acids
o phenylalanine and tryptophan

2. Polar, uncharged amino acids

 Can form hydrogen bonds with water except glycine
 Usually more soluble in water than the non-polar
amino acids
 Good hydrogen-bond forming moieties
o The amide groups of asparagine and
glutamine
o The hydroxyl groups of tyrosine, threonine
and serine
o Sulfhydryl group of cysteine
 Glycine – simplest amino acid
o Has only a single hydrogen for an R group
and is not a good hydrogen bond former TYPES OF AMINO ACIDS
1. Alpha amino acids – the amino acid found in proteins
where the amino group is attached to the 1st carbon atom
3. Acidic amino acids adjacent to the carboxyl group
 R groups contain a carboxyl group
 Aspartic acid 2. Beta amino acids – this type of amino acids is names as
 Glutamic acid such because the amino group is attached to the 2nd carbon
 They have net negative charge at pH 7 atom adjacent to the carboxyl group
 Play an important role in protein functions
 Proteins that bond metal ions for structural or 3. Gamma amino acids – the amino acid where the amino
functional purposes possess metal binding sites group is attached to the 3rd carbon atom adjacent to the
containing one or more aspartate and glutamate side carboxyl group
chains

4. Basic amino acids 3 GROUPS OF AMINO ACIDS

 With net positive charge at neutral pH o Histidine
o Arginine 1. Neutral A.A. – when their molecules have the same
o lysine number of amino and carboxyl groups
 Histidine side chains play important roles as proton
donors and acceptors in many enzyme reactions
 Histidine containing peptides are important
biological buffers

5. *other amino acids

 Occur only rarely in proteins
 Found mainly in the collagen and gelatin proteins
o Hydroxylysine
o hydroxyproline
 • are those amino acids that cannot be synthesized by
the body and are required in the diet.
• Since the body is not capable of synthesizing them,
they must be supplied in our diet if we are to enjoy
normal health

Non-essential amino acids

• are those amino acids that can be synthesized by the
body and need not be included in the diet
Asparagine: Asn, N Memory tool: Remember that ends with an “N”
sound
Arginine: Arg, R Memory tool: The first two letters sounds like
“R”
Aspartic acid: Asp, D Memory tool: Pronounce it as “aspar-Dick” acid
to remember the D
Glutamic Acid: Glu, E Memory tool: The combined abbreviations
spells “gluE”
Glutamine: Gln, Q Memory tool: Pronounce it as “Q-tamin” with
an “n” at the end
Isoleucine: Ile, I Memory tool: “so” was isolated from “isole”
leaving “Ile”
Lysine: Lys, K Memory tool: “K” is next to “L”
Phenylalanine: Phe, F Memory tool: The 1-letter abbreviation sounds
like the first letter of the amino acid

Chemical Properties of Amino Acids

Tryptophan: Trp, W Pronounce it as “T-W-iptophan” to remember
the W
• Reactions are dependent on the numerous different
Tyrosine: Tyr, Y Memory tool: Think of the Y as resembling a reactive groups that are present in the same
“neck-tie” to remind you of “tyrosine” molecule.
• Aliphatic monoamino monocarboxylic acids give all
2. Acidic A.A. – when their molecules have more carboxyl the reactions expected for carboxyl and amino
groups than amino groups groups.
• Aspartic acid (Asp) • characteristic of additional groups that may be
• Glutamic acid (Glu) present. For instance, cysteine give the reactions
characteristic of the sulfhydryl (-SH) group and
3. Basic A.A. – when their molecules have more amino groups tyrosine give the reaction characteristic of phenolic
than carboxyl groups group.
• Lysine* (Lys)
• Arginine (Arg)
• Histidine (His)
*Essential amino acids
Ninhydrin test
• General test for amino acids
• Reagent : triketohydrindene hydrate
• Product: CO2, ammonia and an aldehyde containing
one less carbon than the amino acid
• Positive result: blue or purple color
o proline & hydroxyproline gives yellow color
o Color is produced by the ammonia group
ESSENTIAL VS NON-ESSENTIAL • Alpha amino acid + Ninhydrin =
Essential Amino Acids diketohydrindylidene-diketohydrindamine + CO2 +
aldehyde
 • Amino acid residues – units making up amino acids
Reactions of specific amino acids minus the elements of water
• Proteins – larger chains of amino acids
1. Millon Reaction
• reagent: Millon’s reagent; Hg(NO3)2 in HNO3 w/
trace HNO2
• Positive result: red color
• Specific for Tyrosine

2. Sakaguchi test
By convention, peptide formation is written with the free amino group on the
• reagent: α-naphthol and sodium hypochlorite
left and the COOH on the right. In linear peptides, one end of the chain has a
• Positive result: red color free amino and the other end a free carboxyl group. The amino group end is
• Specific for: guanidine and arginine called the N terminal residue and the other end the C terminal residue

3. Nitroprusside test NOMENCLATURE OF PEPTIDES

• Reagent: sodium nitroprusside [Na2(NO)5.2H2O] in • Named as acyl derivatives of the C-terminal amino
dilute ammoniacal solution acid, the C-terminal unit keeping its complete name
• result: red color • The –ine ending of all but the C-terminal amino acid
• Specific for cysteine and proteins with free sulfhydryl is changed to –yl
group • Except tryptophan (tryptophyl), cysteine (cysteinyl),
glutamine (glutaminyl), asparagine (asparaginyl)
4. Aldehyde reaction • They are listed in the order in which they appear,
• Indole derivative gives strongly colored products starting with the N-terminal amino acid
with a number of aromatic aldehydes. Example: Ala-Tyr-Gly is called alanyltyrosylglycine
• With paradimethylaminobenzaldehyde in H2SO4, a Arg-Glu-His-ala is arginylglutamylhistydylalanine
red violet color is obtained with tryptophan (Ehrlich
reaction). This test can be used for the quantitative Polypeptides
estimation of tryptophan in proteins • The amino acid sequence and chain length give a
polypeptide its biological effectiveness.
5. Folin reaction • The sequence of amino acid residues is essential for
• In alkaline solution, amino acids give a deep red proper polypeptide function.
color with sodium 1,2-naphthoquinone-4-sulfonate • This sequence aligns the side-chain characteristics in
• Used for rapid quantitative estimation of amino acids the proper positions for a specific polypeptide
function.
6. Pauly reaction for Histidine and Tyrosine
• Histidine and tyrosine couple with diazotized
sulfanilic acid in alkaline solution giving a red color

Peptides
• A peptide is an unbranched chain of amino acids,
each joined to the next by a peptide bond
• Since amino acids contain both amino and carbonyl
groups, they combine with each other to form
amides, called peptides.
• The linkage that joins them is known as a peptide PRIMARY STRUCTURES AND FUNCTIONS OF SOME
linkage. BIOLOGICAL POLYPEPTIDES
CLASSIFICATION OF PEPTIDES
• If three amino acid units are included in a molecule,
it is a tripeptide, if 4 a tetrapeptide, if 5 a
pentapeptide and so on
• Oligopeptides – peptide chain of more than 12
residues and less than about 20
• Polypeptides are peptides containing about 40 – 50
amino acid units in a chain
 • Secondary structure result primarily from hydrogen-
bonding interactions b/n different amide linkages
along the protein backbone.

Tertiary structure
• The tertiary structure of the protein arises from the
interactions that take place among the side groups of
polypeptide chains, interactions which cause bending
and folding of the protein molecule
• Maintained by covalent disulfide bonds
• Each type of protein molecule has in its native state,
a characteristic 3-dimensional shape referred to as
conformation (refer to the combined 2o and 3o
structure of the peptide chain
• Tertiary forms the overall 3-dimensional shape of a
protein that results from the interaction between AA
side chains
PROPERTIES OF PROTEINS
2 major groups of proteins
• Globular proteins – named to describe the spherical shape
PROTEINS into which their polypeptide chains are bent and folded as a
Structure of proteins result of tertiary structure
• Proteins contain the elements C, H, O, N and usually • Perform the operational functions in the body by
S (and P) plus traces of Fe, Cu, I, Mn and Zn behaving as enzymes, hormones, antibodies and
• Amino acids – building blocks of proteins transporters (Hgb and serum albumin)
• Fibrous proteins – made up of polypeptide chains arranged
3 Categories of Protein Structure in parallel fashion along a single axis, to yield long fibers or
sheets
Primary Structure • Basic structural unit of connective tissues
• The sequence of amino acids which are joined • Ex. Collagen of tendons and bone matrix, α-keratin of
together to form the polypeptide hair, horn, nails, Elastin (elastic connective tissue)
• The main mode of linkage is the peptide bond • Some proteins (e.g. myosin and fibrinogen) are
• Primary structure is the order of attachment of the intermediate between fibrous and the globular, Rod-
AA to each other through peptide bond. It is always like structures (like the fibrous) and like the globular,
the same regardless of where protein is found in an they are soluble in aqueous salt solutions
organism. i.e. insulin
• It is the most important because it is the protein’s AA Quaternary/quaternary protein structures
sequence that determines its overall shape, function • Protein organization is produced by fitting together
and properties. separate coiled and folded structures to form an
• Crucial that a change of only one AA can drastically aggregate functional structure
alter its biological function. • Ex. Isoenzymes (enzymes with similar but not
• i.e. Sickle-cell anemia val is substituted by glu identical catalytic powers)- LDH, hexokinase,
• phosphatases
Secondary Structure • Oligomeric protein – proteins with more than one
• The peptide chains are folded regularly, the folding chain
resulting from the linkage of the carbonyl group of o Protomers – component chain
one peptide chain with the amine group of another o Ex. Hemoglobin – made up of 4 polypeptide
chain by means of hydrogen bonds chain (2α and 2β), it contains 140 amino
• This hydrogen bonding produces a regular coiled acids in each chain
arrangement called Helix
• α-helix found in α-keratins that make up the hair,
skin and nails of humans
 • Muscles are made up of protein molecules called
myosin and actin
4. Elasticity– the protein elastin, which possesses unique
elasticity and strength, enables the skin, ligament and blood
vessels to stretch and rebound

5. Transport– a large number of proteins fall into this category

• Albumin – transports bilirubin, calcium, fatty acids,
some drugs
• Ferritin and transferrin – transport iron
• Transcortin – cortisol (cortisol-binding protein)
• Hemoglobin – carries oxygen
• Lipoproteins – cholesterol and triglycerides

7. Protection– when a protein from an outside source or

other substance (called antigen) enters the body, the body
makes its own proteins (called antibodies) to counteract the
foreign protein.
• This is the major mechanism the body used to fight
diseases.
• Blood clotting is another protective device carried
out by proteins called fibrinogen. Without clotting,
we would bleed to death from any small wound

8. Storage– some proteins are used to store materials, in the

way that starch and glycogen store energy.
• Examples are casein in milk and ovalbumin in eggs,
which store nutrients for newborn mammals and
birds.
• Ferritin, a protein in the liver, stores iron

9. Regulation – some proteins control the expression of genes

are thereby regulate the kind of proteins manufactured in a
particular cell, and control when such manufacture takes
Proteins and their Biochemical Functions place
1.Structure– for animals, it is structural proteins which are
the chief constituents of skin, bones, hair and fingernails Classification of Proteins on a Nutritional Basis
• Collagen – found in bones – provides the support for Complete proteins
calcium to bind and form the solid structure of the • Proteins that supply all the essential amino acids
bones needed by the human body for normal health
• Keratin – hair and nails • They are derived from animal sources
• They are also referred to as high biological value
2. Catalysis– virtually all the reactions that take place in the protein.
living organisms are catalyzed by proteins called enzymes.
Incomplete proteins
 trypsin – catalyzes hydrolysis of proteins
• Are the proteins that are deficient in one or more
 sucrose – catalyzes the hydrolysis of sucrose
essential amino acids
 dehydrogenase – converts ethanol to acetaldehyde.
• Many proteins especially those from vegetable
 Without enzymes, the reactions would take place so
sources, are incomplete thus the other name which
slowly as to be useless.
low biological value protein.
• For example, protein from corn (maize) is deficient in
3. Movement and Contraction– every time we crook our
lysine
finger, climb stairs, or blink an eye, we use our muscles.
• Muscles expansion and contraction are involved in
every movement we make.
 * Prolamine vs. prolamine – protamine has low MW that are
CLASSIFICATION OF PROTEINS rich in arginine and are found associated especially with DNA
in place of histone in the sperm cells of various animals (as
I. SIMPLE PROTEINS- true proteins found abundantly in both fish)
plants and animals. On hydrolysis with enzymes, they yield α- g.Scleroproteins (Albuminoids)- insoluble in water and
amino acids and their derivatives neutral solvents
Keratin- epidermal tissues
a. Albumins- soluble in water & dil. Neutral salt solution Elastin- ligaments
• coagulated by heat & precipitated by full saturation Collagen- hides, bones & cartilages
with (NH4)2SO4 but not with NaCl except in the
presence of acid II. CONJUGATED PROTEINS- made up of protein molecules
• Members: serum albumin – blood combined with non-protein groups
Lactalbumin- milk
Ovalbumin- egg white a. Nucleoproteins- combinations of histones and protamines
with nucleic acid
b. Globulins- soluble in neutral dil. Salt solution but NOT • soluble in dilute solutions of NaCl and can be
water extracted from the tissues by the use of this solvent;
• -coagulated by heat and can be precipitated from precipitated by acidification
their solutions by half saturation with (NH4)2SO4 • Chromatin
and complete saturation with NaCl • Products obtained from glandular tissues
• -Members: Ovoglobulin- egg white • Germ of grains
Edestin- hempseed
Legumin- peas b. Glycoproteins- proteins with a carbohydrate component
Myosinogen- muscles utilized for lubricating purposes in view of their slimy nature
Serum globulin Mucin- saliva
Tendomucoid- tendons
c. Glutelins- soluble in dil. Acids and alkalies but insoluble in Osseomucoid- bones
neutral solvents • Glycoproteins are not digested by the enzymes of the
• Glutenin- wheat gastro-intestinal tract, thus help in protecting the
• Oryzenin- rice membranes of the tract against digestion.

d. Prolamines- insoluble in ordinary solvent but soluble in c. Phosphoproteins- prosthetic group (H3PO4) joined to the
70% alcohol protein molecule
• not coagulable by heat Casein- milk
• present in plants (e.g. Gliadin- wheat, Zein- corn, Vitellin- egg yolk
Hordein- barley)
d. Chromoproteins- protein compounds with hematin or
e. Histones- soluble in water, dilute acids & alkalies but not in similar pigments
dil. Ammonia Hemoglobin, cytochromes, rhodopsin
• not readily coagulated by heat
• strongly basic and occur in tissues in the form of salt e. Lipoproteins- fatty substances combined with their
- combinations with acid substances like heme of the molecules like lecithin, cephalin, etc.
hemoglobin molecule blood serum, brain tissues, cell nuclei,
Globin- hemoglobin egg yolk and milk
Histone- thymus
Scombrone- mackerel
TYPES OF CONJUGATED PROTEINS
f. Protamines- contain small number of amino acids
• soluble in water & dilute acids and alkalies and are
not coagulated by heat
• strongly basic; form soluble salts with strong mineral
acids
Salmin- salmon sperm
 PHYSICAL AND CHEMICAL PROPERTIES OF PROTEINS
III. DERIVED PROTEINS- substances formed from simple and The number, kind and arrangement of the various amino acids
conjugated proteins within the protein molecule are responsible for the variety of
complex proteins.
A. Primary Protein derivatives- synonymous with denatured However, protein substances share certain COMMON
proteins; have undergone slight intramolecular properties which serve to identify them as a distinct class of
rearrangement through the hydrolytic action of certain biological substances.
physical and chemical agents  when pure, proteins are generally tasteless
 colorless, amorphous compounds
• Proteans- insoluble substances resulting from the
 insoluble in fat solvents & present varied degrees of
preliminary action of water, dilute acids or enzymes
solubility in water, salt solution, dilute acids and
Ex. Myosan (from Myosin)
alkalies
Edestan (from Edestin)
 due to high MW, form non-diffusible colloid solutions
of the emulsoid type
• Metaproteans- products of further hydrolysis;
 proteins are amphoteric; they are labile, readily
soluble in weak acids and alkalies
modified in solution when subjected to alterations in
Ex. Acid metaproteans (acid albuminate)
pH, UVR, heat and organic solvents
Alkali metaproteans (alkali albuminate)
 very reactive & highly specific due to the presence of
side chains & active NH2 groups
• Coagulated proteins- insoluble products resulting
from either the action of heat, alcohol, UVR or even
SOLUBILITY
simple mechanical shaking
Various kinds of proteins differ markedly in their solubility;
Ex. Cooked egg albumin, cooked meat
utilized for group separation and most often for purification of
individual proteins.
B. Secondary Protein derivatives- products of more extensive
hydrolysis
Factors Affecting Solubility:
• mixtures of fragments of original protein varying in
1. Neutral salt-
composition and size
 salting in effect - low concentration of neutral salts
• exhibit common properties (e.g. solubility in water
increases the solubility of proteins
and non-coagulability by heat)
 salting out effect - increase in concentration
decreases solubility
1. Primary proteoses- soluble in water, precipitated by conc.
 The solubility of any substance depends upon the
HNO3 & half saturation with (NH4)2SO4 or ZnSO4; not
relative affinity of solute molecules for each other
coagulated by heat
and for the solvent.
2. Secondary proteoses- precipitated by complete saturation
 Any factor which decreases the interaction of solute
with (NH4)2SO4
molecules will tend to increase solubility.
3. Peptones- soluble in water; precipitated by saturation with
2. Effect of pH- solubility is influenced by pH because of their
certain alkaloidal reagents (e.g. Phosphotungstic acid, Tannic
amphoteric nature
acid)
 solubility is minimum at isoelectric point and
4. Peptides- combinations of 2 or more amino acids, the
increases with increasing acidity or alkalinity
carboxyl group of one being united with the amino group of
3. Effect of Organic solvents
the other
When an organic solvent (which is miscible in water—e.g.
methanol, ethanol, acetone) is added to aqueous solution of
proteins, it lowers the dielectric constant, so that the a. strong acids and bases disrupt hydrogen
electrical forces between the charged particles in the solution bonds and salt bridges; prolonged action
are increased, thus diminishing the solubility of proteins leads to actual hydrolysis of peptide bonds
 Selective separation of the constituent proteins of a b. organic solvents interfere with R-group
mixture can be achieved by proper adjustment of pH, interactions because these solvents also can
temperature, alcohol concentration, protein form hydrogen bonds; quickly denature
concentration and salt concentration kept at low proteins in bacteria, killing them
level.
 E.g. Fractionation of plasma with this procedure
produces fractions which are of clinical significance:
Fibrin film & foam – used for surgery
Albumin – treatment of shock, nephrosis, cirrhosis
Globulin – passive immunization PRECIPITATION
Agglutinins – for blood typing By Acids- due to presence of the NH2 group in their
molecules, amino acids have basic properties and form
ACTION OF HEAT insoluble salts with acids.
 when burned, proteins decompose and liberate a
characteristic odor of burned hair or feather Organic acids- Trichloroacetic, Phosphomolybdic,
Phosphotungstic, Picric, Tannic acids are used as precipitants
Denaturation- the process by which solution of proteins  Tannic acid & Picric acid are used for treating burns
undergo slight intramolecular rearrangements when they are because they produce astringent effect on the
heated between 38 to 60 degrees Celsius, giving rise to tissues, diminish secretion of mucous membranes
changes in chemical, physical and biologic properties. and prevent absorption of toxins. They are also
 Believed to be due to the unfolding of the administered in some forms of gastro-intestinal
characteristic folded structure of polypeptide chain. irritation to relieve diarrhea.
 Reversible process; the unfolded molecule will return  Inorganic acids also precipitate protein. Nitric acid is
to its native form when conditions become favorable used for detecting the presence of proteins in the
(Renaturation, Refolding or Annealing) urine (Heller’s test).
 Renders the protein insoluble at isoelectric point,
causing it to precipitate (Flocculation) By salts of Heavy metals (alkali metals)- Hg, Ag, Pb
proteins behave like acids by virtue of the carboxyl radical;
Coagulation- If flocculated protein is heated further, the form insoluble salts with alkaline metals
clumped chains become matted together in a mass which is  In metallic poisoning, antidotes like egg white and
insoluble, not only at isoelectric point but also over the entire milk are given. They form insoluble precipitates
pH range which can be removed subsequently by means of a
 a process involving the linkage of adjacent protein stomach tube.
molecules by means of side chain Hydrogen bonds
 coagulated protein is hard to dissolve & when By Alcohol- Maximum precipitation occurs at isoelectric point
dissolved, it differs from the original protein from (when proteins are electrically neutral). This accounts for the
which it is derived; process is irreversible. antiseptic property of alcohol.
* 95% alcohol has less germicidal property compared to 70%
Other Factors which bring about Denaturation: alcohol. It readily coagulates proteins and coagulum forms a
1. high pressure protective coating on the surface of bacteria preventing
2. Low temperature further penetration of the alcohol.
3. UVR – operates very similarly to the action of heat *Sterilization- 90 % alcohol
(i.e. sunburning) *Wound- 70% alcohol
4. surface action
5. mechanical shaking or violent whipping – causes
molecules PROTEINS
in globularMETABOLISM
shapes to extend to longer
lengths, which then entangle (i.e. beating egg with
white into meringue)
6. chemical agents (e.g. acids, alkalies, organic solvents, PROTEIN METABOLISM
alcohol, etc.). Protein forms the primary constituent not only of the cell but
also of such regulatory agents as hormones and enzymes. It
confers upon the tissue a sort of biological specificity; that is,
the protein of a particular tissue is distinct and different from
those of other tissues. This is so because complex proteins are
made up of varying proportions of essential and non-essential
amino acids depending upon the tissue, organ or specie.

ESSENTIAL OR INDISPENSABLE AMINO ACIDS:

- Methionine - Leucine
- Threonine - Phenylalanine
- Lysine - Tryptophan
- Valine - Histidine
- Isoleucine - Arginine
 The term essential and non-essential relates only to
dietary requirements, not in relation to importance
in metabolism.
 The study of protein metabolism is centered on the
metabolism of amino acids, mostly concerned with
Metabolic pathways of absorbed Amino acids
the fate of the amino nitrogen and those of the non-
1. Synthesized into new tissue proteins including enzymes and
nitrogenous residues.
hormones
 The amino nitrogen enters in the formation of urea 2. Synthesized into plasma proteins
while the non-nitrogenous residues participate
 Liver is the site for biosynthesis of plasma proteins,
either in the carbohydrate or lipid metabolism.
albumin, globulin and fibrinogen
ABSORPTION OF AMINO ACIDS
Synthesis is dependent upon the presence of indispensable
 After a complete hydrolysis in the gastro-intestinal amino acids and is increased when there is generous supply of
tract, the proteins are split into their component dispensable AA.
amino acids. 3. Synthesized into liver proteins
 amino acids are absorbed mainly in the small 4. Synthesized into non-protein nitrogenous components of
intestines through the portal circulation, and only various cells
slightly through the lymphatics.  Purine, pyrimidine, porphyrins, glutathione, creatine,
 The absorption of amino acids is very rapid so that thyroxin, nicotinic acid, etc.
the maximum concentration in the blood is attained 5. Decarboxylated with formation of physiologically active
30 to 50 minutes after eating. amines
There is rapid removal of the absorbed amino acids from the 6. Deaminated, with the subsequent formation of urea and
blood. The amino acids are quickly disposed and appear in all oxidation of α-ketoacid or its conversion into carbohydrate or
tissues and organs of the body. This is evident from the fact fat
that the amino acid nitrogen level is kept more or less 7. Take part in the glucose-alanine cycle
constant between 4-8 mg/100 ml of blood plasma.  Prevents the fluctuations in the blood glucose level
between meals
FACTORS THAT AFFECT DISTRIBUTION OF AA IN METABOLIC
 Functions
REACTIONS
 To carry amino groups from skeletal muscles
1. Convalescing or growing individuals – for
to the liver to be converted into urea for
constructions of new proteins
excretion
2. The availability of new carbohydrate and lipid -
 To provide the working muscles with blood
influence the amount of total caloric requirement
glucose made by the liver form the carbon
which must be supplied by amino acids
structure of alanine
3. The pattern of amino acid mixture supplied to the
tissues
4. The influence of hormones in modifying the direction
DYNAMIC ASPECTS OF NITROGEN METABOLISM
and the rate of certain metabolic reactions
NITROGEN BALANCE- quantitative difference between the
nitrogen intake (from food) and the nitrogen output
(represented by nitrogen lost in the urine and feces)
POSITIVE NITROGEN BALANCE- intake exceeds the output;
this is found whenever new tissues are being synthesized as in
growing young, convalescence, pregnancy, etc.

NEGATIVE NITROGEN BALANCE- output exceeds the intake;

this is found in:
1. inadequate intake of proteins as in fasting,
malnutrition, diarrhea;
2. increased catabolism as in fevers, infections,
wasting diseases; and
3. increased loss of body proteins as in lactation,
albuminuria

UTILIZATION OF INORGANIC NITROGEN

The only form of inorganic nitrogen, which can be utilized by
living cells is ammonia.

Fixation of ammonia
1. Glutamic Acid synthesis FATE OF AMMONIA:
a-ketoglutaric acid + NH3 + NADH + H+ Glutamic acid The ammonia liberated during the deamination process is
+ NAD+ + H2O disposed off in several ways:
Enzyme: Glutamic acid dehydrogenase
• • The α-amino group of glutamic acid can be 1. It enters the general ammonia pool of the body and
transferred to other keto-acids by transamination process may be drawn upon either for anabolic or catabolic
• • Provides a mechanism for synthesis of other amino purposes. It may be used in the reductive
acids amination of keto acids derived from CHO to form
new amino acids.
TRANSAMINATION 2. Since ammonia is toxic in large concentrations, it is
being detoxified by synthesis to glutamine.
Is a biochemical reaction that involves the interchange of the 3. Ammonia may be excreted directly into the urine.
amino group of an a-AA with the keto group of an a-keto acid. 4. Ammonia may enter the ornithine cycle to form
urea.

UREA CYCLE: (excess nitrogen)

Mammals utilize urea as the major vehicle for excretion of
surplus nitrogen (ureotelic).
On the basis of their observations, Krebs and Henseleit
proposed a cyclic mechanism for the synthesis of urea
2. Synthesis of Glutamine involving the amino acids ornithine, citrulline and arginine in
Glutamic acid + NH3 + ATP Mg++ Glutamine + ADP + Pi + H2O the presence of the enzyme arginase, which catalyzes the
Enzyme: glutamine synthetase irreversible hydrolysis of arginine to ornithine and urea.
 Glutamine serves as a means of presenting to an
enzyme an unprotonated nitrogen atom at reduction
level of NH3
 Glutamine serves as a store of ammonia

3. Carbamoyl Phosphate synthesis

CO2 + NH3 + ATP + H2O Carbamoyl PO4 + ADP + Pi + 3
H+
Enzyme: Carbamoyl phosphate synthetase
 Carbamoyl PO4 becomes available to the cells for
carbamylation of amino groups as in the synthesis of
citrulline from ornithine
  Threonine
 Glycine
 Serine
 Cysteine
Five amino acids are degraded to acetyl CoA without
forming pyruvate
 Lysine
 Tyrosine
 Phenylalanine
 Tryptophan
 Leucine
Five amino acids forming α-ketoglutarate
 Glutamate
 Glutamine
 Arginine
1. Nitrogen enters the urea cycle in the form of ammonium  Proline
ion.  Histidine
2. A reaction between ammonium ion and CO2 produces Amino acids forming succinyl-CoA
Carbamoyl phosphate in a reaction that requires two • Methionine
molecules of ATP for each molecule of carbamoyl phosphate. • Valine
3. Carbamoyl phosphate reacts with Ornithine to form • Isoleucine
Citrulline. (ornithine transcarbamoylase) • Aspartate and Asparagine are deaminated to oxaloacetate
 The reactions of the cycle at this point take place in • Aspartate + α-ketoglutarate oxaloacetate +
the mitochondrion. glutamate
 Citrulline is then transported to the cytosol. • Asparagine + H2O Aspartate + NH4+

4. A second nitrogen enters the urea cycle when aspartate

reacts with citrulline to form argininosuccinate
(arginosuccinate synthase) in another reaction that requires
ATP (AMP and Ppi are produced in this reaction).
 The amino group of the aspartate is the source of the
second nitrogen.
5. Argininosuccinate is split to produce arginine and
fumarate. (argininosuccinate lyase)
6. Finally, arginine is hydrolyzed to give Urea (arginase) and to
regenerate ornithine, which is transported back to the
mitochondrion.
7. The synthesis of fumarate is a link between the urea cycle
and the citric acid cycle.
 Fumarate
LIPIDS: is an intermediate
CLASSIFICATION, of theAND
PROPERTIES citricDIGESTION
cycle, and it
can be converted to oxaloacetate.
 A transamination reaction can convert oxaloacetate Lipids
to aspartate, providing another link between the two  organic substances made up of fatty acids and their
cycles naturally existing compounds and derivatives.
 Relatively insoluble in water and ordinary solvents.
Degradation of Amino Acids for Energy Production o Soluble in nonpolar/organic solvents (e.g.
ether, chloroform, acetone & benzene)
Five amino acids are degraded to Acetyl CoA by way of
pyruvate LIPIDS: Diverse Functions
 Alanine
  Straight chain - products of hydrolysis of waxes
TRIGLYCERIDE / Neutral FAT  Alcohols containing the b-ionone ring – vitamin
 Secondary energy source A and some carotenoids
o Serves as a thermal insulator  Sterols
o Protects tissues from physical trauma Miscellaneous
 Aliphatic hydrocarbons - iso-octadecane from liver
CHOLESTEROL  Squalene - hydrocarbons in shark liver and human
 Precursor of biological hormones sebum
 Source of bile acids  Carotenoids
 Component of the Cell membrane  Vitamin D, E and K

PHOSPHOLIPIDS
 Component of the Cell membrane
 Associated with vital life processes (e.g. CNS)

FIVE CATEGORIES ON THE BASIS OF LIPID FUNCTION

 Energy storage lipids (TAG)
 Membrane lipids (phospholipids, sphingoglycolipids
and cholesterol)
 Emulsification lipids (bile acids)
 Messenger lipids (steroid hormones and
eicosanoids)
 Protective coating lipids (biological waxes)

Lipids: Classification
1. SIMPLE LIPIDS- esters of fatty acids with various alcohols.
Neutral fats- glycerol esters
Waxes- esters of higher alcohols
• True waxes FAT: esters of fatty acids with glycerol
•Cholesterol esters CH2 – O – CO – R1
• Vitamin A esters
• Vitamin D esters CH – O – CO – R2

2. COMPOUND LIPIDS - contain other radicals CH2 – O – CO – R3

Phospholipids - contain HyPO, and nitrogenous base Glycerol Fatty Acid Chains
 Lecithin - choline as nitrogenous base
FATS
 Cephalin - ethanolamine
 R1, R2 and R3: the same fatty acid chain =SIMPLE
 Lipositol - Inositol
GLYCERIDE (Examples: Palmitin, Stearin aria Olein)
 Phosphatidyl serine - serine
 R1, R2 and R3: different fatty acid chains=MIXED
 Plasmalogen - fatty acid group is replaced by a fatty
GLYCERIDE
aldehyde (resemble lecithins &cephalins )
 Rearrange FA = variety of glycerides
 Sphingomyelin - sphingosine and choline as
nitrogenous bases
Examples of Fats
 Glycolipids – contain carbohydrate and nitrogenous
 Animal fats- Oleic, palmitic and stearic acids
base
 Mutton fat- more stearic and less oleic acid than
 Ill-defined lipids- amino lipids and sulfo-lipids, having
pork
NH2 and SO2 groups respectively
 Butter fat- mainly palmitic and oleic acids with small
amount of butyric and caproic acids
3. DERIVED LIPIDS- products of hydrolysis of land II; but still
 Human fat- mostly oleic acid; yellowish tinge is due
exhibiting the general physical characteristics of lipids
to carotene and xanthophylls pigments
 Saturated and unsaturated FA
 Mono and di-glyceride
 Alcohols
FATTY ACIDS
  Tail: long hydrocarbon chain (hydrophobic)  UNSAT. FA: # C atoms +; # of double bonds + -enoic
:4-24 C atoms
 Head: carboxyl (hydrophilic) o 18 C: Octadecanoic / Stearic
: Octadecenoic / Oleic
 SATURATED FATTY ACIDS:
 Acetic series FATTY ACIDS
 General formula: CH (CH)n COOH SOURCES
 low MW (≥10 C atoms)= liquid at RT; low MP and SAT. FA: fats from animal sources, butter, lard, coconut and
volatile. peanut oil
 The rest are solids; high MP and non-volatile. Those UNSAT. FA: oils mostly from plant sources
with ≤4 C are miscible with H2O in all proportions.
Hydroxy and Cyclic acids:
 Chaulmoogra oil: the ethyl esters and sodium salts of
Hydnocarpic and Chaulmoogric acid are used in the
treatment of Leprosy.
 oPhthioic acid: shown to produce proliferation of
epitheloid and giant cells; probably the agent
responsible for the manifestations of TB.

Some important FA

Omega fatty acids: polyunsaturated

 Main source: Fish and fish oil
 lower plasma triglycerides
 Have beneficial effects for CHD because of their anti-
thrombotic action.
 "Brain oil" - Alzheimer's disease

Polyunsaturdied Fatty Acids (PUFA)

UNSATURATED FATTY ACIDS:  Have a carbon chain in which two or more carbon-
 oThe degree of unsaturation = number of double carbon double bonds are present
bonds  Omega Fatty Acids
 Double bonds in fatty acids usually have the cis  Fish and fish oil are the most concentrated
configuration. source but maybe found in some plants
 Unstable did reactive (H20, H2, 02,Br, or 12). (EPA,DPA, DHA)
 insoluble in ordinary solvents.  they lower plasma trigilcerides
 liquid at RT and non-volatile.  they have beneficial effects on coronary heart
 The greater the degree of unsaturation, the lower disease because of their thrombotic action (they
are the melting and congealing points reduce platelet aggregation and blood clots) 

Essential FA
 Linoleic, Linolenic acid and Arachidonic acid
 Dietary deficiency:
 impaired growth and reproduction
 skin disorders (e.g. eczema and dermatitis)
 excessive thirst
 kidney damage (severe cases)

Eicosanoids
 The biochemical derived from the fatty acid
arachidonic acid
 Prostaglandins are the best known of the eicosanoid
NOMENCLATURE: class. Which also includes the leukotrienes,
 SAT. FA: # of C atoms + -anoic prostacyclins and thromboxanes
  Cell membranes release arachidonic acid in  COX-2 inhibitors - inhibit prostaglandin synthesis for
response to a variety of circumstances, including pain control while only minimally affecting the
infection and allergic reactions stomach
 Drugs that control leukotriene synthesis
Prostaglandins  Aspirin - prevent heart attack and strokes, probably
 Lipids that contain 20 carbon atoms including a five by blocking thromboxane synthesis
membered ring structure  Cortisone - blocks the release of arachidonic acid
 First isolated from seminal fluid and from the and therefore stops inflammation
prostate gland (originally thought to be the only
prostaglandin, a single substance secreted by the Glycerol
male genital tract  Simplest trihydric alcohol commonly known as
 Many different prostaglandins were found to be glycerine
present in almost all animal tissues  Oily, colorless, heavy liquid with sweet
 According to one theory, aspirin kill pain by inhibiting  taste
the synthesis of prostaglandin (PG)  By-product in the manufacture of soap
 They regulate a number of biological activities and  Component of fat responsible for the (+) acrolein test
thus exhibit hormonal behavior (e.g. known to cause (easily detected by its characteristic acrid odor) 
smooth muscles to contract)
*A clinical use for some prostaglandins is to USES OF GLYCEROL
induce labor  Widely used both for pharmaceutical and cosmetic
 Prostaglandins and some of their precursors are also preparation due to its solubility, hygroscopic nature
thought to cause inflammation. The anti- and solvent action
inflammatory, antipyretic and analgesic actions of  When glycerol undergoes hydrolysis under alkaline
aspirin and other non-narcotic analgesics are conditions, it is split into glyceride and
believed to result from their ability to interfere with dihydroxyacetone
the synthesis of prostaglandins.  lt can reduce Cu++ to Cu+
 The non-narcotic analgesics inhibit the action of the  Positive for Benedict's and Fehling's test
enzyme prostaglandin synthetase thus reducing the  when treated with HNOs, it forms nitroglycerine
formation of excess prostaglandins and the pain, which is used in making dynamites and smokeless
fever, and inflammation powders
o used in medicine as vasodilation drug in the
Arachidic acid treatment of hypertension
prostaglandin synthetase o in the body, glycerol is liberated during digestion
of fat, when free glycerol is absorbed and
PG(G2) and PG (H2) metabolized, it yields a caloric value similar to
(Pain causing) glucose

Thromboxanes General Properties of Fats

o Formed by platelets in the blood stream, which act as Physical Properties
vasoconstrictors and stimulate platelet aggregation as an Neutral fats
initial step in blood clotting  characteristic greasy feel and penetrates through
paper producing a translucent spot
Leukotrienes  odorless, tasteless and colorless (when pure)
o Formed by a variety of white blood cells as well as other  color due to pigments present
tissues and cause many symptoms associated with an allergy  insoluble in ordinary solvents
attack
 soluble in organic solvents (chloroform, benzene,
ether, hot alcohol)
Group of drugs used fer eicosanoid control
 NSAID (non-steroidal anti-inflammatory drugs) - Neutral Fats (cont.)
block the oxidation of arachidonic acid to form
 non-volatile, produce characteristic crystals with
prostaglandin and thromboxanes
definite melting point
Examples: ibuprofen. Ketoprofen
 neutral fats containing large amounts of unsaturated
fatty acids are liquid at room temperature, hence
they are called oils. In the presence of catalysts
 (finely divided nickel) take up hydrogen and become Unsaturated fats (oils) are generally liquids. It is possible to
solid obtain solid, saturated fats by catalytic hydrogenation of oils
 • CH2(CH2)4СН=CНСН2СН=CH(CH2)7СООН + Н2 Ni
CH3 (CH2)16СООН 4. Rancidification
 principle involved in the manufacture of artificial o Fats are neutral in reaction, but when exposed to air for
butter (oleomargarine) from vegetable oils some time, they become acidic due probably to hydrolysis
which results in the liberation of volatile fatty acids. The
subsequent oxidation of the fatty acid chains with the
formation of odoriferous volatile aldehydes and ketones

 Factors that contribute to the rapid onset of rancidity

Enzyme Heat Light Moisture Bacteria
 Fats containing oleic acid become rancid quite easily
 fat floats on water because it has a lower specific  To prevent rancidity in products containing
gravity than the latter. When shaken vigorously with unsaturated fats, compounds are added to serve as
it, fats broke up into fine particle forming a antioxidants (eg. vit. E and phenols)
temporary emulsion. Soap, acacia, albumin or bile  Rancidity results in the destruction of the accessory
salts are used as emulsifying agents (lower the food factors like carotene, vit. A and vit. E. Rancid fat
surface tension) therefore is not only unpalatable but may even be
toxic
Chemical Properties
1. Hydrolysis 5. Halogenation
 the hydrolysis of a fat molecule generates 3  The halogens chlorine or bromine rigadily add across
molecules of fatty acid a glycerol molecule the double bonds of unsaturated fatty acids
 catalysts: acids, enzymes (lipases), superheated  Halogenation of an unsaturated fat is used to
steam estimate its degree of unsaturation. The IODINE
NUMBER is expressed in terms of the number of
ex: Stearin + 3H20 + acid/enzyme 3 stearic acid + grams of iodine that would be absorbed by 100g of
glycerol fat
Steroids
2.Saponification  Derivatives of the hydrocarbon ring system
• Base-catalyzed hydrolysis of a fat, when the base NaOH, the  One type of steroid found in living cells is a STEROL, a
sodium salts of the fatty acids are produced compound in which a hydroxyl (OH) group is
attached to the steroid ring system
Cholesterol
 cyclopentanoperhydrophenathrene
 Most abundant sterol in animal tissues
 Present in nerve tissue, blood and bile (the greenish
fluid secreted by the liver that aids in the digestion of
fat)
 Sodium soaps - hard
 Greek "chole" for bile and "steros" for solid o
 Potassium soap - soft
Gallstones are nearly pure cholesterol (80 - 90%)
 Ca and Mg - insoluble soap
 In the body, cholesterol is the precursor of biological
 Detergency - property of the soap of causing and
steroids/steroid hormones which perform crucial
maintaining the emulsification of the greasy
body functions (e.g. bile salts, androgen, estrogen,
substances
etc)
o The cleansing property of soap is attributed
to its emulsifying property Medical Importance: CHOLESTEROL

3. Hydrogenation
Atherosclerosis - metabolic disease that leads to deposits of Phospholipids
cholesterol and other lipids (plaque) on the inner walls of the  Type of lipid found in all biological membranes
arteries  Composed of
 arterial passages become narrower, lose elasticity o 2 fatty acids
and the ability to accommodate the volume of blood o 1 glycerol
pumped by the heart. o 1 phosphoric acid
 Plaque inner walls o f the heart to become o 1 alcohol
rough rather than the normal smooth surface
coronary thrombosis heart attack due to blood General structure of phospholipids
clots
 Cholesterol (and other lipids) must be packaged for
transport because lipid aggregates in the aqueous Important Phosphoglycerides
bloodstream.  Cephalin (ethanolamine phosphoglyceride;
phosphatidyl ethanolamine)
LIPOPROTEINS:  The A group in the formula is derived from
Low density lipoprotein (LDLs) ethanolamine, HOCH2CH2NH2 (or cholamine)
 associated with deposition of "cholesterol" on the  Found in brain tissue
walls of arteries.  Cephalin is the thromboplastic substance which
 LDLs transport cholesterol and triglycerides from initiates the process of blood coagulation
the liver to peripheral tissues.
 They enable fats and cholesterol to move within the Lecithin (choline phosphoglyceride, phosphatidyl choline)
water-based solution of the blood stream.  has a structure in which the A residue is derived from
High density lipoprotein (HDLs) the cation choline
 associated with carrying "cholesterol" out of the  present in great quantities in the egg yolk, liver and
blood system, and is more dense/more compact nervous tissue (arachidonic acid is one of its
than LDL. component fatty acid)
 HDLs act as cholesterol scavengers by collecting  freshly prepared lecithin is waxlike, turns brown on
cholesterol and returning it to the liver where it exposure to air; soluble in organic solvents and yields
produces bile salts. acrolein when heated with dehydrating agent
Very low density lipoproteins (VLDLs)  2 fatty acids + 1 phosphoric acid + 1 glycerol + 1
 A type of lipoprotein made by the liver. choline
 VLDLs enable fats and cholesterol to move within the
water-based solution of the bloodstream. Lysolecithin
 Lysolecithin is a toxic substance that causes
destruction of BC (hemolysis).
 Some snake venoms and insect poisons are toxic
Fat Soluble Vitamins because they contain enzymes capable of catalyzing
 vitamin A (vision) the hydrolysis of lecithin to lysolecithin.
o Rhodopsin – can see in the dark  •In the food industry, lecithins are used as
o Opsin + retina – can see in the light emulsifiers (agents that break-up mixtures of oil and
 vitamin D (Ca2+ uptake, bone Ca2+ and phosphate) water into an emulsion of tiny drops of oils
o bone growth suspended in water)
 vitamin E (tocopherols) (antioxidant)
o antioxidant- fight free radicals; least toxic Sphingolipids
 vitamin K (cofactor for posttranslational modification  Also found in all membranes are particularly
of blood clotting proteins -- formation of g- abundant in brain and nerve tissue
carboxyglutamate, Gla)  Sphingomyelin and glycolipids are both classified as
o “koagulation”- blood clotting sphingolipids because they include a backbone of
sphingosine, an amino alcohol
7-dehydrocholesterol  Replacing one of the amino H with a fatty acid acyl
 Cholesterol derivative which is converted to an active group R-CO produces an amine of sphingosine
form of vitamin D (Vitamin D3 or cholecalciferol) known as ceramide (basic structural units for all
when skin is exposed to sunlight sphingolipids)
  Fatty acid esters (resistant to hydrolysis) are
absorbed and deposited in the fat depot.
 Unabsorbed fats / fatty acid esters are excreted in
the feces (STEATORRHEA)

Intestinal Absorption
• 40% of ingested TG - hydrolyzed to fatty acids and
glycerol
• 3-10% - absorbed as TG; the rest are partially
hydrolyzed to β-monoglyceride.
• Glycerol (water-soluble)- absorbed via the portal
Cerebroside route.
 A glycolipid found in the membranes of brain tissue • fatty acids (water-insoluble) are predominantly
as its name suggests absorbed via the intestinal lymph(appear in the
 Ganglioside form of triglycerides)
o Glycolipids in which the CHO that is
attached to ceramide is much more complex FATTY ACID MICELLE
than a monosaccharide • Consists of bile acids, free fatty acids and
o Found on the outer surface of nerve cells Monoglycerides
• Fatty acid chains are pointed towards the center
Tay-Sach's disease (a hereditary disorder) • Formation is essential for intestinal absorption
 the enzyme (hexosaminidase A) needed to break
down a ganglioside is deficient leading to the Triacylglycerol Storage
accumulation of the latter in the brain and spleen. • Adipose tissue - the only tissue in which free TAGs
 This accumulation leads to neurological occur in appreciable amounts
deterioration, which occurs after the first month of • In other types of cells and in the bloodstream, TAGs
life and leads to death within 5 years. are part of lipoprotein particles.
 one of many genetic disorders in lipid metabolism
that have been discovered in humans

DIGESTION OF FATS Complete Hydrolysis

LIPID METABOLISM

ACTIVATION & ENTRY of FATTY ACIDS into the

MITOCHONDRIA

Beta-oxidation
1. Activation of Fatty acids (outer membrane)
DIGESTION OF FATS Incomplete Hydrolysis • Thiokinases: enzymes catalyzing the formation of fatty acyl
CoA esters

(fatty Acyl CoA)

2. Transfer to Carnitine
Higher fatty acids have limited ability to cross the inner
membrane
Enzyme: Fatty Acyl CoA:Carnitine fatty acid transferase

Intestinal Absorption 3. Transfer to Intramitochondrial CoA

 Complete hydrolysis is NOT a prerequisite to Enzyme: Carnitine-f.a.transferase
absorption. - Fatty acyl carnitine + CoA Fatty acyl CoA + Carnitine
- Mitochondrial acyl thiokinase: makes possible the direct • CHO, glycerol of fat, glucogenic amino acids
utilization of GTP generated in the mitochondria.
METABOLISM OF PHOSPHOLIPIDS
Components: 1 H3 PO4; 1glycerol; 2fatty acids; nitrogenous
base
• plasma membrane
• Lecithin & Sphingomyelin

METABOLISM OF PHOSPHOLIPIDS
Absorption:
• Dietary & endogenous phospholipids may be
FATTY ACID DEGRADATION absorbed as such or hydrolyzed by lecithinase from
• After the activation, the fatty acyl CoA ester pancreatic juice
undergoes enzymatic degradation. LECITHIN fatty acids + glyceryl-phosphoryl- choline
• B-Oxidation: shortening of the fatty acid chain by 2C CEPHALIN fatty acids + glyceryl-phosphoryl-cholamine
atoms at a time (4 successive steps)
• The glyceroPO4linkage may be hydrolyzed in the
1. Dehydrogenation with FAD intestinal mucosa by phosphodiesterase.
2. Reversible hydration
3. Dehydrogenation w/ NAD PHOSPHOGLYCERIDE SYNTHESIS (in ER)
4. Reaction with CoA 1. De novo synthesis in which phosphatidyl serine serves as a
• yields Acetyl CoA and a fatty acid derivative of CoA precursor for other phosphatides
which is shorter by 2C atoms (Thiolysis) - CDP diacyl glycerol : common precursor of phospholipids
- Phosphatidyl serine = P. ethanolamine = P. choline
KETONES & KETOGENESIS
• formation of ketone bodies (normal intermediary 2. Utilization of Exogenous Choline (Salvage pathway)
products): liver. • CHOLINE - base component of Phospholipids
• Normal physiologic conditions: fatty acid • Synthesis of Lecithin
degradation and synthesis occur without significant
accumulation of the intermediates
Steroids
• Compounds with the steroid nucleus (consists of
four fused carboxylic rings)
• This nucleus contains 17 carbon atoms in one five-
membered and three six- membered rings:
Cyclopentanoperhydrophenanthrene (Sterol)

Cholesterol
• the most important and abundant sterol in the body
• precursor for the biosynthesis of bile salts, steroid
hormones and vitamin D in the skin.

CHOLESTEROL METABOLISM
• Route of absorption: lymphatics.
• Its reduction products (formed through bacterial
KETONE BODIES activity) Coprosterol and Cholestanol are poorly
• Acetoacetic acid (20%) absorbed, and are found abundantly in the feces.
• B-hydroxybutyric acid (78%) • Cholesterol in the intestines is derived from food,
• Acetone (2%) intestinal secretions and bile

KETOGENIC- substances which form ketone bodies • BIOSYNTHESIS OF CHOLESTEROL:

• Fatty acids & the following amino acids: Isoleucine, • Conversion of Acetyl Co to Mevalonic Acid (3CoA)
leucine, phenylalanine & tyrosine • Conversion of Mevalonic acid to Squalene (6 carbon)
ANTIKETOGENIC • Conversion of Squalene to Cholesterol (30 carbon)
SYNTHESIS OF CHOLESTEROL ESTERS:
• Most of the cholesterol in the tissues is present in
esterified form
• 1. Cholesterol + Fatty acid CoA Cholesterol ester
+ COA
• 2. P. choline + Cholesterol Lysophosphatidyl
Choline + Chole ester