UNIT FOUR

Cellular Metabolism and Metabolic Disorders

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Objectives

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 4.1 Cellular metabolism
 Metabolism: totality of chemical reactions that occur in living organism.

The primary functions of metabolism are:

 acquisition & utilization of energy
 Removal of waste products

Types of metabolic pathway

In metabolism, a series of chemical reactions in which the product of one

reaction is the substrate for the next reaction is called a metabolic pathway.
 Anabolism- energy requiring biosynthetic pathways
 Catabolism- degradation of fuel molecules and the production of energy
for cellular function
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 Cont…
 The reactants and products of these chemical reactions are
metabolites.
 The major classes of metabolites include:

Proteins
Carbohydrates
Nucleotides
Lipids
Coenzymes, and cofactors.

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 Classes of compounds encompass an enormous diversity of
molecular structures, physicochemical properties, functions, and
abundances.
 The most common criteria for this distinction rely on the
hydrophilic (polar) and hydrophobic (nonpolar) nature of
metabolites.
 These metabolites include most of the reactants and products
involved in cellular respiration
 At the cellular level of organization, the main chemical processes
of all living matter are similar
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 4.1.1 Enzymes and their role in metabolism

• Enzymes are protein catalysts that speed biochemical reactions by facilitating

the molecular rearrangements that support cell function.

• Enzymes are biological catalysts

• They are not consumed or altered during the reaction
• They increase the rate of a reaction by lowering the activation energy
barrier.
• The reactant usually binds to the enzyme forming a transition complex
that stabilizes the transition state.
• The interaction between enzyme and substrate is very specific.
Specificity may be for a class of compounds or for a particular
compound.
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Eg. Hexokinase / glucokinase 6
 4.1.2 Chemical nature and classification of enzymes

• All known enzymes are proteins with the exception of recently

discov­ered RNA enzymes.
• Some enzymes may additionally contain a non-protein group.
• On the basis of differences in chemical nature, the enzymes may be
described as follows:
 Simple enzyme: It is made up of only protein molecules not
bound to any non-proteins.eg. pepsin and trypsin
 Conjugate Enzymes: It is an enzyme which is formed of two parts
a protein part called apoenzyme and a non-protein part named
cofactor.
.
7
 Cont…

 The complete conjugate enzyme, consisting of an apoenzyme

and a cofactor, is called holoenzyme.
• The protein component of this Holoenzymes is called
Apoenzyme
• The non-protein component of the holoenzyme is called a
cofactor

e.g. Ca, Mg, Zn, Co, etc

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 Cont…
COENZYMES
 Coenzymes are derivatives of vitamins without which the enzyme
cannot exhibit any reaction.
 Coenzymes are called co substrate because the changes that take
place in substrates are complimentary to the changes in
coenzymes.
 „The coenzyme may participate in forming an intermediate
enzyme-substrate complex
 Example: NAD, FAD, Coenzyme A

9
 Cont…
Metal ions in enzymes
 Many enzymes require metal ions for their activity.
Example.
 Metal-activated enzymes-form only loose and easily dissociable
complexes with the metal and can easily release the metal without
denaturation.
 Metalloenzymes hold the metal tightly on the molecule and do not release
it even during extensive purification.
Properties of Enzymes
Active site: the active site binds the substrate, forming an enzyme-substrate
(ES) complex. ES is converted to enzyme-product (EP); which subsequently
dissociates to enzyme and product.
Enzyme turnover number :refers to the amount of substrate converted per unit time
10
Isoenzymes (Isozymes)
These are enzymes having similar catalytic activity,
act on the same substrate and produces the same product but
originated at different site
Example: LDH (Lactate dehydrogenase) exists in five different forms
each having four polypeptide chains. H= Heart and M=Muscle.

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 Cont…

Classification of Enzyme
There are 6 main classes based on the type of reaction
catalyzed.
This makes up the first number of the enzyme identity.
1. Oxidoreductase
2. Transferase
3. Hydrolase
4. Lyase
5. Isomerase
6. Ligase
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 The Six Classes of Enzymes

1. Oxidoreductases (dehydrogenases)
• Catalyze oxidation-reduction reactions

13
 2. Transferases

• Catalyze group transfer reactions

14
 3. Hydrolases

• Catalyze hydrolysis reactions where water is

the acceptor of the transferred group

15
 4. Lyases
• Catalyze lysis of a substrate, generating a
double bond in a nonhydrolytic, nonoxidative
elimination (Synthases catalyze the addition to
a double bond, the reverse reaction of a lyase)

16
 5. Isomerases
• Catalyze isomerization reactions

17
 6. Ligases (synthetases)
• Catalyze ligation, or joining of two substrates
• Require chemical energy (e.g. ATP)

18
 Major classes of Enzymes

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 Factors Affecting Enzyme Activity

Physical and chemical factors are affecting the enzyme

activity. These include
1. Temperature
2. pH
3. Substrate concentration
4. Enzyme concentration
5. Enzyme inhibitors
6. Cofactors
7. Coenzymes

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 Effect of temperature
 Optimal temperature (To) is the characteristic T at which an enzyme
has the maximal catalytic power.
 35 ~ 40C for warm blood species.
 Higher T will denature the enzyme.
 Breaking bonds within the enzyme will cause the active site to
change shape

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 pH - Acidity and Basicity
 Optimal pH is the characteristic pH at which the enzyme has the maximal
catalytic power.
 PH 7.0 is suitable for most enzymes.

 Particular examples:
pH (pepsin) = 1.8
pH (trypsin) = 7.8

 H+ and OH- ions are charged and therefore interfere with hydrogen and
ionic bonds that hold together an enzyme
 This interference causes a change in shape of the enzyme
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 Concentration of substrate

• At fixed enzyme concentration, pH and temperature the activity of

enzymes is influenced by increase in substrate concentration.
• An increase in the substrate concentration increases the enzyme activity
till a maximum is reached.
• Further increase in substrate concentration does not increase rate of
reaction.
• This condition shows that as concentration of substrate is increased, the
substrate molecule combine with all available enzyme molecules at their
active site till not more active sites are available (The active Sites
become saturated).
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 Enzyme Concentration

• The rate of the reaction is directly proportional to enzyme

concentration at all substrate concentration.
• Increasing enzyme concentration will increase the rate of
reaction, as more enzymes will be colliding with substrate
molecules.
• However, this too will only have an effect up to a certain
concentration, where the enzyme concentration is no longer
the limiting factor.
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 Enzyme inhibitors
Two examples of Enzyme Inhibitors
a. Competitive inhibitors: are chemicals that resemble an
enzyme’s normal substrate and compete with it for the
active site.
b. Noncompetitive inhibitors:
Inhibitors that do not enter the active site, but bind to
another part of the enzyme causing the enzyme to change
its shape, which in turn alters the active site.
Control of Metabolism
 Is necessary if life is to function.
 Controlled by switching enzyme activity "off" or "on” or
separating the enzymes in time or space

25
 Cont’d…
Types of Control
1. Switching on or off the genes that encode for specific
enzyme production
2. Allosteric sites
3. Feedback inhibition
4. cooperativity
Allosteric Regulation
 The control of an enzyme complex by the binding of a regulatory
molecule.
 Regulatory molecule may stimulate or inhibit the enzyme
complex.
 Allosteric site is a specific receptor site on some part of the
enzyme molecule away from the active site
 When activated, this site changes the shape of the enzyme to
inhibit it or to stimulate it

26
 Cont’d…

Feedback Inhibition
 When a metabolic pathway is switched off by its end-product.
 End-product usually inhibits an enzyme earlier in the pathway.
 Prevents the cell from wasting chemical resources

27
 Cont’d…
Cofactors
 Inorganic substances (zinc, iron, copper) are sometimes
need for proper enzymatic activity.
 Non-protein helpers can bond to the active site of enzymes
to help in reactions
 Example:
Iron must be present in the quaternary
structure of hemoglobin in order for it
to pick up oxygen.
Coenzymes
 Organic molecules that act as cofactors which help
enzymes.
 Examples:
 vitamins
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 Substrate Binding and Enzyme Action
• The first step in a enzyme catalyzed reaction is the formation
of the enzyme-substrate complex. This is represented by the
equation:
• E + S = ES = E + P.
• The region of the enzyme where the substrate binds is called
as the active site. This consists of a substrate binding site and
the catalytic site.
• The active site is usually a cleft or pocket created by the
unique tertiary structure of the enzyme protein
• Enzyme specificity is due to specificity of substrate binding
driven by substrate and enzyme 3D structure
• The ES complex is stabilized in the transition state by non-
covalent interactions between substrate and the aa in the
active site. 29
Enzymatic reaction steps

1. Substrate approaches active site

2. Enzyme-substrate complex forms
3. Substrate transformed into products
4. Products released
5. Enzyme recycled
 MECHANISM OF ACTION OF ENZYMES

Lock: Key model of enzyme action implies that the active

site of the enzyme is complementary in shape to that of its
substrate, i.e. the shape of the enzyme molecule and the
substrate molecule should fit each other like a lock and
Key

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• Induced fit model In 1958 by Daniel Koshland.
- Enzyme structure is flexible, not rigid.
- Enzyme and substrate adjust the shape of the active site to bind substrate.
- The range of substrate specificity increases.
- A different substrate could not induce these structural changes and no
catalysis would occur.

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 4.3 Bioenergetics and biosynthesis
4.3.1. Cellular respiration
• Most living organisms obtain energy by catabolism during cellular
respiration.
• This catabolic process can be divided into 3 phases.
• Phase I - Breakdown of large complex biomolecules like polysaccharides…
• The chemical reactions occurring during this stage do not release much
energy.
• Phase II - These building blocks are usually oxidized to a common
intermediate, acetyl - CoA.
• Additionally, pyruvate or other citric acid cycle intermediates may also be
formed (in glycolysis and other pathways).
• Phase III – This consists of the citric acid followed by electron transport
and oxidative phosphorylation.
• Energy released by electron transport to O2 is coupled to ATP synthesis.
• This cycle is responsible for the release of much energy ( TCA cycle and
ETC)
 Cellular respiration

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 Molecular structure of ATP

 Adenosine triphosphate (ATP) is a nucleoside triphosphate used in

cells as a coenzyme.
 It is often called the "molecular unit of currency" of intracellular
energy transfer.
 ATP transports chemical energy within cells for metabolism.
 It is one of the end products of photophosphorylation, cellular
respiration, and fermentation and used by enzymes and structural
proteins in many cellular processes, including biosynthetic
reactions, motility, and cell division.
 Cont..
 Substrate level phosphorylation, oxidative phosphorylation
in cellular respiration, and photophosphorylation in
photosynthesis are three major mechanisms of ATP
biosynthesis.
• Metabolic processes that use ATP as an energy source
convert it back into its precursors.
• ATP is therefore continuously recycled in organisms.
• One molecule of ATP contains three phosphate groups, and
it is produced by a wide variety of enzymes, including ATP
synthase, from adenosine diphosphate (ADP) or adenosine
monophosphate (AMP) and various phosphate group
donors.

ATP consists of a base, in this case adenine (red), a ribose (magenta) and a
phosphate chain (blue).
 4.3.1.1 Anaerobic respiration

• Anaerobic respiration is a form of respiration using electron

acceptors other than oxygen.
• Anaerobic metabolic processes do not require oxygen.

Glycolysis
 Glycolysis (from glycose, an older term for glucose + -lysis
degradation) is the metabolic pathway that converts glucose
C6H12O6, into pyruvate, CH3COCOO− + H+.
 The free energy released in this process is used to form the high-
energy compounds ATP (adenosine triphosphate) and NADH
(reduced nicotinamide adenine dinucleotide).
• Glycolysis does not require or consume oxygen.
• The terms "aerobic glycolysis" and "anaerobic glycolysis"
refer to glycolysis in the presence or absence of oxygen,
respectively.
• Glycolysis occurs, with variations, in nearly all organisms,
both aerobic and anaerobic.
• The wide occurrence of glycolysis indicates that it is one of
the most ancient known metabolic pathways.
• It occurs in the cytosol of the cell.
The entire glycolysis pathway can be separated into two phases:
1. The Preparatory Phase -investment phase
 The first five steps are regarded as the preparatory (or investment)
phase.
 since they consume energy to convert the glucose into two three-carbon
sugar phosphates (G3P).
2. The Pay Off Phase – in which ATP is produced.
 Characterized by a net gain of the energy-rich molecules ATP and
NADH.
 This yields 2 NADH molecules and 4 ATP molecules, leading to a net
gain of 2 NADH molecules and 2 ATP molecules from the glycolytic
pathway per glucose.
 Substrate-level phosphorylation is the mechanism to produce ATP
during glycolysis.
Biochemical logic for the presence of regulatory steps
 The existence of more than one point of regulation indicates that
intermediates between those points enter and leave the glycolysis
pathway by other processes.
 For example, in the first regulated step, hexokinase converts
glucose into glucose-6-phosphate. Instead of continuing through the
glycolysis pathway, this intermediate can be converted into glucose
storage molecules, such as glycogen or starch.
Energy Investment Phase
 Energy Payoff Phase

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 4.3.1.2 TCA cycle and ETC
Aerobic respiration
• One fate of pyruvate is that it enters to TCA cycle for complete oxidation.
But there are intermediate processes: The Oxidation of Pyruvate to
form Acetyl CoA for Entry Into the Krebs Cycle
• 2 NADH's are generated (1 per pyruvate)
• 2 CO2 are released (1 per pyruvate)
• The Krebs Cycle (citric acid cycle, TCA cycle)
 is considered as central pathway of aerobic metabolism, as it serves
two purposes-bioenergetics and biosynthesis
1. Bioenergetics:The cycle carries out complex degradation of acetyl
group in acetyl - CoA to CO2, resulting in release of energy (ATP
or GTP) and reducing power (NADH and FADH2).
2. Biosynthesis: It supplies precursors for several biosynthetic
pathways of amino acids, pyrimidines, purines etc
Example:- α-ketoglutarate and oxaloacetate are used for synthesis of a
number of amino acids like glutamic acid, asparatic acid etc
• Acetyl - CoA is the starting material for fatty acid biosynthesis.
• 6 NADH's are generated (3
per Acetyl CoA that enters)
• 2 FADH2 is generated (1 per
Acetyl CoA that enters)
• 2 ATP are generated (1 per
Acetyl CoA that enters)
• 4 CO2's are released (2 per
Acetyl CoA that enters)

Therefore, the total numbers of

molecules generated in the
Oxidation of Pyruvate and the
Krebs Cycle is: 8 NADH, 2
FADH2, 2 ATP and 6 CO2
 7.3.2 Electron transport chain

• In aerobic respiration, electron transport is the final step in the

break-down of glucose

• It also is the point at which most of the ATP is produced

• High-energy electrons and hydrogen ions from NADH and FADH2

produced in the Krebs cycle are used to convert ADP to ATP

• The maximum net Energy Production from Aerobic
Respiration is 36-38
04/08/2021 chemiosmotic theory (ETC) 48
Biosynthesis
 Biosynthesis is a multi-step, enzyme-catalyzed process where substrates
are converted into more complex products in living organisms.
 In biosynthesis, simple compounds are modified, converted into other
compounds, or joined together to form macromolecules.
 This process often consists of metabolic pathways.
 Some of these biosynthetic pathways are located within a single cellular
organelle, while others involve enzymes that are located within multiple
cellular organelles.

 Examples of these biosynthetic pathways include the production of

lipid membrane components and nucleotide.
49
 Cont…
 The prerequisite elements for biosynthesis include: precursor
compounds, chemical energy (e.g. ATP), and catalytic enzymes
which may require coenzymes (e.g.NADH, NADPH).
 These elements create monomers, the building blocks for
macromolecules.
 Some important biological macromolecules include: proteins,
which are composed of amino acid monomers joined via peptide
bonds, and
 DNA molecules, which are composed of nucleotides joined via
phosphodiester bonds. 50
Requirements of Biosynthesis
I. Photosynthesis
 Energy is transformed all around us every day.
 Similarly, some autotrophs convert light energy into chemical
energy through photosynthesis.
The importance of photosynthesis
 The processes of all organisms, from bacteria to humans require
energy and to get this energy, many organisms access stored energy
by eating food.
 Carnivores eat other animals and herbivores eat plants. But where
does the stored energy in food originate?

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 Cont’d…

 Photosynthesis is essential to all life on earth.

 It is the only biological process that captures energy from outer space
(sunlight) and converts it into chemical energy in the form of
Glyceraldehyde3-phosphate (G3P), which in turn can be made into
sugars and other organic compounds such as proteins, lipids, and
nucleic acids.
 Plants use these compounds in all of their metabolic processes.

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 The process of photosynthesis

 During photosynthesis, molecules in leaves capture sunlight and

energize electrons, which are then stored in the covalent bonds of
carbohydrate molecules.
 That energy within those covalent bonds will be released when they
are broken during cell respiration.
 Photoautotrophs
 Are organisms(plants, algae, and some bacteria) which have a
capability of performing photosynthesis and they use light to
manufacture their own food.
53
 Cont’d…
 Heterotrophs: are organisms, such as animals, fungi, and
most other bacteria, they must rely on the sugars produced by
photosynthetic organisms for their energy needs.
 Chemoautotrophs: are very interesting group of bacteria
synthesize sugars, not by using sunlight's energy, but by
extracting energy from inorganic chemical compounds.
 The importance of photosynthesis is not just that it can capture
sunlight's energy.

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 Cont’d…

Other variant of photosynthesis

 Commonly known photosynthetic processes is the one known as
oxygenic photosynthesis.
 The other type is termed as anoxygenic photosynthesis.
 The general principles of anoxygenic and oxygenic photosynthesis
are very similar,
 But oxygenic photosynthesis is the most common and is seen in
plants, algae and cyanobacteria.
 During oxygenic photosynthesis, light energy transfers electrons
from water (H2O) to carbon dioxide (CO2), to produce
carbohydrates.
 In this transfer, the CO2 is "reduced," or receives electrons, and
the water becomes "oxidized," or loses electrons. Ultimately,
oxygen is produced along with carbohydrates.
55
 Cont’d…
 On the other hand, anoxygenic photosynthesis uses electron donors
other than water.
 The process typically occurs in bacteria such as purple bacteria
and green sulfur bacteria, which are primarily found in various
aquatic habitats.
The photosynthetic apparatus
 Plastids
 Photosynthetic eukaryotic organisms contain organelles called
plastids in their cytoplasm.
 Plastids generally contain pigments or can store nutrients.
 Colorless and nonpigmented leucoplasts store fats and starch,
while chromoplasts contain carotenoids and chloroplasts contain
chlorophyll.
56
 Cont’d…
 Photosynthesis occurs in the chloroplasts; specifically, in the grana and stroma
regions.
 The grana is the innermost portion of the organelle; a collection of disc-shaped
membranes, stacked into columns like plates.
 The individual discs are called thylakoids. It is here that the transfer of electrons
takes place.
 Chloroplasts are similar to mitochondria, the energy centers of cells, in that they
have their own genome, or collection of genes, contained within circular DNA

57
 Cont’d…
Pigments
 Pigments are molecules that bestow color on plants, algae and
bacteria, but they are also responsible for effectively trapping
sunlight.
 Pigments of different colors absorb different wavelengths of light.
There are 3 main group of pigments.
1. Chlorophylls
 These green-colored pigments are capable of trapping blue and red
light.
 Chlorophylls have three subtypes, dubbed chlorophyll a,
chlorophyll b and chlorophyll c.
 There is also a bacterial variant aptly named bacteriochlorophyll,
which absorbs infrared light.
 This pigment is mainly seen in purple and green bacteria, which
perform anoxygenic photosynthesis. 58
 Cont’d…
2.Carotenoids: these red, orange or yellow-coloured pigments absorb
bluish-green light. Examples of carotenoids are xanthophyll (yellow) and
carotene (orange) from which carrots get their color.
3.Phycobilins: these red or blue pigments absorb wavelengths of light that
are not as well absorbed by chlorophylls and carotenoids. They are seen in
cyanobacteria and red algae.
 Antennae is Pigment molecules are associated with proteins, which
allow them the flexibility to move toward light and toward one another.
 A large collection of 100 to 5,000 pigment molecules constitutes
antennae. These structures effectively capture light energy from the sun,
in the form of photons. 59
 Cont’d…
Reaction centers: the pigments and proteins, which convert light energy
to chemical energy and begin the process of electron transfer, are known as
reaction centers.
The photosynthetic process
 The reactions of plant photosynthesis are divided into those that require
the presence of sunlight and those that do not.
 Both types of reactions take place in chloroplasts: light dependent
reactions in the thylakoid and light-independent reactions in the stroma.
 Light-dependent reactions :When a photon of light hits the reaction
center, a pigment molecule such as chlorophyll releases an electron.
 The released electron manages to escape by traveling through an electron
transport chain, which generates the energy needed to produce ATP and
NADPH.
 The "electron hole" in the original chlorophyll pigment is filled by taking
an electron from water. As a result, oxygen is released into the
atmosphere.
60
 Cont’d…

 light-independent reactions (also called dark reactions and known as the

Calvin cycle): Light reactions produce ATP and NADPH, which are the rich
energy sources that drive dark reactions.
 Although NADPH and ATP provide cells with large amounts of energy,
these molecules are not stable enough to store chemical energy for long
periods of time.
 Thus, there is a second phase of photosynthesis called the Calvin cycle in
which energy is stored in organic molecules such as glucose.

Three chemical reaction steps make up the Calvin cycle:

 Carbon fixation,
 Reduction and
 Regeneration. 61
 Cont’d…

 The carbon atoms from carbon dioxide are ''fixed,'' when they

are built into organic molecules that ultimately form three-

carbon sugars.

 These sugars are then used to make glucose or are recycled to

initiate the Calvin cycle again.

62
63
 C3 Plants

• During the Calvin cycle, CO2 is used to build sugars

• C3 plants (soybeans, wheat, rice) only use the Calvin

Cycle to fix CO2

– Given this name because CO2 is initially made into a

three carbon compound.

• These plants operate during the day

64
 Alternative Pathways

 The environment in which an organism leaves can impact the

organism's ability to carry out photosynthesis.
 Environments in which the amount of water or carbon dioxide
available is insufficient can decrease the ability of a
photosynthetic organism to convert light energy into chemical
energy.
 For example, plants in hot, dry environments are subject to
excessive water loss that can lead to decreased photosynthesis.
 Many plants in extreme climates have altered native
photosynthesis pathways to maximize energy conversion.
65
 Cont..

 Some plants that are found in hot, dry environments

have adaptations that minimize water loss while still
allowing photosynthesis to take place:

C4 plants

CAM plants

 They do not immediately enter into the Calvin cycle

like C3 plants
66
 C4 Plants

 Stomata partially closed during the day

 Have a specialized pathway that captures low

levels of CO2 & build 4 carbon compounds that
enter the Calvin cycle

Examples: sugarcane, corn, crabgrass

67
C4 Plants

68
 C AM Plants

 CAM (crassulacean acid metabolism) plants open

stomata at night and close them during the day

 Have a specialized pathway that takes in CO2 at night

and makes a variety of organic acids

Then during the day, enzymes break down these

organic acids, releasing CO2 that enters into the Calvin
cycle

 Examples: cacti and pineapples

Why is C3 photosynthesis so inefficient?
69
CAM Plants

70
 4.4. Metabolic disorders, diagnosis
and treatments
 Metabolism is the breaking down of food to its simpler
components
 Metabolic disorders occur when these normal processes become
disrupted.
 Disorders in metabolism can be inherited, in which case they
are also known as inborn errors of metabolism, or they may be
acquired during your lifetime.
Inherited metabolic disorders
 They are one cause of metabolic disorders, and occur when a
defective gene causes an enzyme deficiency.
 These diseases, of which there are many subtypes, are known as
inborn errors of metabolism.
 Metabolic diseases can also occur when the liver or pancreas do
71
not function properly.
 Cont’d…
 There are numerous examples of inherited metabolic
disorders, classified based on the type of food-related
building block that they affect, including amino acids,
carbohydrates, and fatty acids.
 Inherited causes of metabolic disorders include:
 Carbohydrate disorders; examples include Diabetes
insipidus, hereditary fructose intolerance, galactosemia,
pyruvate metabolism disorders, von Gierke‟s disease, McArdle
disease, Pompes disease, and Forbes‟ disease.
 Fatty acid oxidation defects; examples include Gaucher‟s
disease, Niemann-Pick disease, Fabry‟s disease, and medium-
chain acyl-coenzyme A dehydrogenase (MCAD) deficiency .
 Amino acid disorders; examples include Tay-Sachs disease,
phenylketonuria, tyrosinemia, maple syrup urine disease, and
homocystinuria. 72
 Cont’d…
Other causes of metabolic disorders
 Metabolic disorders can be due to other factors, such as a
combination of inherited and environmental factors.
 Some of the conditions that can cause metabolic disorders
include:
 Alcohol abuse, Diabetes (chronic disease that affects your
body's ability to use sugar for energy)
 Diuretic abuse, Gout (type of arthritis caused by a buildup of
uric acid in the joints)
 Ingestion of poison or toxins, including excessive aspirin,
bicarbonate, alkali, ethylene glycol, or methanol
 Kidney failure, Pneumonia, respiratory failure, or
collapsed lung
 Sepsis (life-threatening bacterial blood infection) .
73
 Cont’d…
Risk factors of metabolic disorders
 A number of factors increase the risk of developing metabolic
disorders.
 Not all people with risk factors will get metabolic disorders.
Risk factors for metabolic disorders include:
 certain chronic medical conditions, such as lung or kidney disease
and Diabetes.
 Family history of genetic metabolic disorder
 Age- the risk of metabolic syndrome increases with age.
 Obesity and lack of exercise
 Hormone imbalance
 Insulin resistance: a situation in which a body cannot use insulin
properly.
74
 Cont’d…
Diagnosis of metabolic disorders
 Metabolic syndrome is more effectively diagnosed by testing different
blood markers (specific markers of insulin resistance), obesity
(especially abdominal obesity), high blood pressure, and lipid
abnormalities.
 Specifically, metabolic syndrome is diagnosed if any three of the
following five markers are present:
 Elevated waist circumference: 40 inches or more for men; 35 inches
or more for women
 Elevated triglycerides: 150 mg/dL or higher
 Reduced high-density lipoprotein (HDL) levels (''good'' cholesterol):
less than 40 mg/dL in men; less than 50 mg/dL in women
 Elevated blood pressure: 130/85 mm Hg or higher or are already
taking blood pressure medications
 Elevated fasting glucose: 100 mg/dL or higher or are already taking
glucose-lowering medications . 75
 Cont’d…
Treatments of metabolic disorders

 The treatment approach for metabolic disorders depends on

the specific disorder.
 Inherited metabolic disorders are often treated with nutritional
counselling and support, periodic assessment, physical therapy,
and other supportive care options.
 Multiple treatment options are available for inherited metabolic
disorders and examples include:
 bone marrow transplantation,
 enzyme replacement therapy in selected patients,
 gene therapy in selected patients,
 medications to reduce symptoms, such as pain or low blood sugar,
mineral supplementation, nutritional counselling, surgery to relieve pain
or symptoms, vitamin supplementation and etc.

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 Cont’d…
Potential complications of metabolic disorders
 Complications of untreated metabolic disorders can be serious,
even life threatening in some cases.
 The risk of serious complications can be minimized following
the treatment plan designed by health care professional.

 Complications of metabolic disorders include:

 organ failure/dysfunction,
 seizures and tremors, and
 unconsciousness and coma. 77