Page 1 of 86

LIST OF ABBREVIATIONS
AA Amino Acids
Ach Acetylcholine
ADH Antidiuretic Hormone
ADP Adenosine Diphosphate
AMP Adenosine monophosphate
ATP Adenosine Triphosphate
DNA Diribonucleic Acid
ES Enzyme Substrate
FAD Flavin Adenine Dinucleotide
FADH Flavin Adenine Dinucleotide Hormone
GDP Guanosine Diphosphate
GNG Gluconeogenesis
GTP Guanosine Triphospate
HDL High Density Lipoproteins
LDL Low Density Lipoproteins
NAD Nicotinamide Adenine Dinucleotide
NADH Nicotinamide Adenine Dinucleotide Hormone
PEP Phosphoenolpyruvate
PFK PhosphoFructoKinase
RNA Ribonucleic Acid
UDP Uridyl Diphosphate
VLDL Very Low Density Lipoproteins

Page 2 of 86
Module Introduction
Basic biochemistry module is designed to equip the learner with
knowledge, skills and attitude to enable them to develop a good
understanding of nutrition, conduct their research project,
participate in nutrition and health related studies.
The prerequisite modules include; Human anatomy and
physiology, Principles of human nutrition, and physical sciences.
The module takes 60 contact hours: 37 hours for theory and 23
hours for practicals. Learners undertaking this module will have
both theory and practical assessments. Formative assessment will
be in the form of continuous assessment tests, assignments,
clinical and field assessments and promotional examination
whereas summative assessment will be done in form of final
qualifying examination.

Page 3 of 86
Module Competences
Provide the learner with basic concept of biochemistry and biochemical
metabolism; and to appreciate the role of biochemistry in nutrition; health
and disease

Module Outcomes
1. Demonstrate understanding of metabolism of major nutrients
2. Explain the role of enzymes in nutrient metabolism and in provision of
energy
3. Explain the mechanism of protein synthesis
4. Demonstrate understanding on the role of hormones in nutrient
metabolism and regulation
5. Explain the disorders of abnormal metabolism and hormones
disturbances

Module Learning Strategies

Lectures, demonstration, group discussions, individual assignments and case
studies

Module Learning Logistics/Resources

Laptop computer, projector, white board and white board markers

Module Assessment
CAT(s) accounts for 40% of the total marks
End of semester examination account for 60% of the total marks

Page 4 of 86
UNIT 1: INTRODUCTION
Unit objectives
By the end of the lesson, the learner should be able to;
1. Define the term biochemistry
2. State the roles of biochemistry
Biochemistry is the study of science which explore structures and functions
of living organisms at molecular level. It involves investigation of isolated
molecules. It is concerned with structures and properties of biomolecules
found in living systems in order to understand structure-function
relationships
1.1 Role of biochemistry in provision of energy and synthesis of
various substances
 Human beings are chemotrophs in that they obtain their free energy by
oxidizing organic compounds (carbohydrates, lipids, proteins).
 The organic compounds are converted to a common intermediate acetyl-
CoA whose acetyl group is then converted to CO 2 and H2O through the
action of the citric acid cycle and oxidative phosphorylation.
 To maintain health, there should be an optimal intake of a number of
these biomolecules and therefore understanding of proper nutrition will
depend on a greater aspect on the knowledge of biochemistry.
 Metabolism generates energy as adenosine triphosphate (ATP), reducing
power, and building blocks for biosynthesis.
 ATP is the universal currency of energy with a high phosphoryl-transfer
potential and is generated from the oxidation of fuel molecules and its
hydrolysis drives reactions by changing the equilibrium of coupled
reactions.
1.2 Role of hormones in regulation of metabolism
Body hormone take part in the oxidation of fuel molecules(degradative) that
generates reducing power in the form of:
1. NADH for mitochondrial electron transport chain
2. NADPH for biosynthetic processes.
Page 5 of 86
This separation ensures that metabolic processes are thermodynamically
favorable in both directions. It allows for reciprocal regulation

UNIT 2: CARBOHYDRATES
Unit objectives
By the end of this lesson the learner should be able to:
1. Identify and classify carbohydrates
2. Name and draw structures of common monosaccharides and
disaccharides
3. List the sources and uses of common monosaccharides and
disaccharides
4. Explain reactions of monosaccharides
5. Explain the physical and chemical properties of common
polysaccharides

Carbohydrates according to their structures, they are polyhydroxyl

aldehydes or ketone or any other substance that yield these substances
upon hydrolysis.
Carbohydrates have a general formula of (CH2O)n, where n is equal or greater
than ≥3, meaning that the simplest carbohydrate has a structure of C 3H6O3.

2.1 Classification of carbohydrates

They are classified as monosaccharide, disaccharides and polysaccharides.
1. Monosaccharides
They are simple sugars consisting of a single polyhydroxyl aldehyde or
ketone unit i.e. the back bone is un-branched single bonded chain.
There are three ways of classifying monosaccharides:-
 Can be classified depending on the numbers of carbon atom present in
their structure e.g. triose contains three carbon, tetrose contains four
carbon atoms, pentose contains five carbon atoms and hexose contains
six carbon atoms
 Depending on the carbonyl functional group present on the compound
which can either be a ketone or aldehyde. Those with ketone functional
Page 6 of 86
 group are known as ketose and those with aldehyde functional group are
known as aldose.

(Aldose) (ketose)

 Sometimes both classifications are used e.g. aldopentose meaning that it

has five carbon atoms and an aldehyde functional group where as
ketohexose has six carbon atoms and ketone functional group.
2.2 Structure of common monosaccharide

Examples of common monosaccharides

2.3 Properties of carbohydrates (stereochemistry)

Is the orientation of atoms in space, so monosaccharide shows both
stereoisomerism and structure isomers.
Stereoisomer refers to compounds that differ from one another due to
configuration of their atoms. The first type of isomerism that is experienced
by monosaccharide is known as enantiomer.
Enantiomers are molecules that have non-superimposable mirror image. Non
superimposability is brought about by chirality of molecules.
Page 7 of 86
Chiral carbon atom is any carbon atom that is single bonded to four different
substituent groups. Enantiomers are chemically and physically identical.
They will have the same solubility, boiling and melting point.

2.3.1 Epimers
This is also a stereoisomerism experienced by monosaccharide. They are
compounds that defer from one another in relation to their configuration
around a single chiral carbon atom e.g. glucose and mannose in respect to
carbon number 2. Glucose and galactose with respect to carbon number
four. But D-galactose and D-mannose are not epimers, because they differ
with more than one chiral carbon atom.
I. D- AND L- configuration
D- and L- configuration refers to the last chiral carbon atom(penultimate),the
carbon atom from the highly oxidized carbon atom in the fischer projection
formular. If the hydroxyl group projects to the right the sugar has a D-
configuration and when it is projected to the left then it has an L-
configuration. Most sugars in animals occurs in D-configuration because the
enzymes concerned with these metabolism are specific for this configuration.

II. Haworth projection

Occur in two forms:-
a) Furan form e.g. ribose and fructose
b) Pyran e.g. glucose
c)
A Haworth projection is thermodynamically stable as compared to fischer
projection. When sugar exists in Haworth projection we say that they are

Page 8 of 86
thermodynamically stable. If in fischer projection formulae the hydroxyl
group is on the right the it will go below in the Haworth projection.

Cyclization of open chain glucose into pyranose ring structures.

Cyclization of open chain fructose into furanose ring structures

2.3.2 Anomers
These are carbohydrates that differ only in the configuration around the
carbonyl carbon atoms. Beta D-glucose and alpha D-glucose are anomers
because they differ in configuration around the anomeric carbon atom. The
orientation of OH on the anomeric carbon can either be alpha or beta. Alpha
configuration is where the orientation of OH on the anomeric carbon is below
Page 9 of 86
the plane of the molecule. And if OH is above the plane then we have the
beta anomer.

2.4 Disaccharides
These are carbohydrates which consist of more than two monosaccharide
units linked together by glycosidic bond. They are obtained upon hydrolysis
of polysaccharides.
Glycosidic bond is formed by hydrolysis of 2-OH of adjacent monosaccharide
unit. The link between the two monosaccharide can be head-tail or head-
head. Head-head will result to reducing sugars.
Examples of disaccharides include;
i. Maltose is a disaccharide that result from partial hydrolysis of starch. It
is composed of two glucose residues which are condensed together
through a glycosidic linkage. The linkage exist when carbon one of one
residue and carbon number four of another residue are linked. The
linkage is known as alpha 1,4 glycosidic bond.
Maltose is a reducing sugar.

Glycosidic bond formed between the C1 hydroxyl group α-D-

glucose and the C4 hydroxyl group of another α-D-glucose to
form maltose

ii. Cellobiose:- is a disaccharide obtained from a partial hydrolysis of

cellulose. It is made up of glucose unit linked by beta 1,4 glycosidic
bond.

Page 10 of 86
 iii. Lactose:- this is a sugar bonding milk made up of glucose and
galactose residues linked together by beta 1,4 from carbon number
one of galactose to carbon number four of glucose.

+ H2O

D-galactose
D-Glucose D-glucose
D-Galactose Lactose
Lactose Water
Water

Glycosidic bond formed between the C1 hydroxyl group of β-D-

galactose and the C4 hydroxyl group of β-D-glucose to form lactose.

iv. Sucrose:- it is known as table sugar obtained from sugar cane. It is a

disaccharide of glucose and fructose residues linked together by
alpha 1,2 glycosidic bond from carbon number one of glucose to
carbon number 2 of fructose. It is a non reducing sugar.

Glycosidic bond formed between the C1 hydroxyl group

α-D-glucose and the C2 hydroxyl group of fructose to
form sucrose

Page 11 of 86
2.5 Polysaccharides
They are polymers of monosaccharide linked through glycosidic bond. Can
be classified depending on the composition and function.
Functional
i. Storage polysaccharide
Can act as a storage form of energy in an organism which can be
glycogen in animal and starch in plants.
ii. Structural function
They maintain the structure of living organism e.g. chitin and
cellulose.
Composition
i. Homopolysaccharide:- consists of a repeating unit of a single
monosaccharide repeatedly linked together through a specific
glycosidic bond e.g. glycogen, starch and cellulose
ii. Heteropolysaccharide:- consists of two or more of different unit
repeated monosaccharide e.g. heparin
Examples of polysaccharide
II.5. 1Starch
Is a storage homopolysaccharide of glucose units made up of two
components:-
i. Amylose:- unbranched straight chain of glucose units linked by
alpha 1,4 glycosidic bond. Amylose consist of about 250-300
glucose unit.
ii. Amylopectin:- is soluble in water and is a highly branched polymer
of a glucose unit. The glucose units in the straight chain are joined
together by α 1,4 glycosidic bond while branched are joined to the
straight chain by α 1,6 glycosidic bond. The branching occur after
20-30 monosaccharide units.

Page 12 of 86
 Representative partial structure of amylose.

 1  6  Glycosidicbond

Representative partial structure of amylopectin.

2.5.2 Glycogen
Is a storage polysaccharide found in many body tissues e.g. muscles. The
structure of glycogen is similar to that of amylopectin except that it is more
highly branched. The branching occurs between 8-10 glucose residues. The
main chain is linked by alpha 1,4 glycosidic bond and it has numerous alpha
1,6 glycosidic bonds which provide many branch points along the chain.
2.5.3 Cellulose
It is the most common and occurring polymer of glucose unit found in the
cell wall of plants. The bond holding the glucose units are beta 1,4 glycosidic
bonds.
 Cellulose is a linear polymer of β-D-glucose units linked through β(1→4)
glycosidic bonds.
 A typical cellulose molecule contains about 3000 glucose units.
 Cellulose is a structural component of plant cell wall.
 As opposed to starch, cellulose cannot be digested by humans because
humans lack the enzyme to break the β(1→4) bond.
 Cellulose acts as a dietary fiber in the human diet.

Page 13 of 86
 Representative partial structure of cellulose.

2.6 Carbohydrate metabolism (glycolysis)

 Glycolysis is the pathway through which glucose is oxidized to either
lactate or pyruvate.
 Under aerobic conditions, pyruvate is formed in a process known as
aerobic glycolysis.
 pyruvate undergoes oxidative decarboxylation and is converted into
acetyl coenzyme A (Acetyl-CoA).
 Acetyl-CoA then enters the Krebs cycle or tricarboxylic acid cycle
(TCA) or citric acid cycle where it under goes a series of reactions to
produce energy.
 When oxygen is depleted, e.g. during prolonged vigorous exercise,
the dominant product is lactate and the process is known as
anaerobic glycolysis.
 Aerobic glycolysis of glucose to pyruvate requires two equivalents
of ATP to activate the process, with the subsequent production of
four equivalents of ATP and two equivalents of NADH.
 Thus, conversion of one mole of glucose to two moles of
pyruvate is accompanied by the net production of two moles
each of ATP and NADH.

Glucose + 2 ADP + 2 NAD + + 2 Pi → 2 Pyruvate + 2 ATP + 2 NADH + 2

H+

2.6.1 The Individual Reactions of Glycolysis

Page 14 of 86
The process of glycolysis consists of 10 reactions (steps) which can be
divided into 2 separate phases.
i. chemical priming phase requiring energy in the form of ATP,
ii. energy-yielding phase.
 In the chemical priming, glucose is phosphorylated and consequently
converted to glyceraldehyde-3-phosphate.
o This phase uses 2 equivalents of ATP to convert glucose to
fructose 1,6-bisphosphate (F1,6 BP).
 In second phase F1,6 BP is degraded to pyruvate, with the
production of 4 equivalents of ATP and 2 equivalents of NADH.
 Glycolysis consists of 10 individual reactions which are discusses in the
following section
I. Hexokinase reaction
 The ATP-dependent phosphorylation of glucose to form
glucose 6-phosphate (G6P) is the first reaction of glycolysis, and is
catalyzed by tissue-specific isoenzymes known as hexokinases.

II. phosphorylation accomplishes two goals:
(i) It converts nonionic glucose into an anion that is
trapped in the cell, as cells lack transport systems for
phosphorylated sugars.
(ii) the otherwise biologically inert glucose becomes
activated into a labile/reactive form capable of being further
metabolized.
III. Phosphohexose Isomerase reaction
 G6P is isomerized to fructose 6-phosphate (F6P). Phosphohexose
Isomerase is also known as phosphoglucose isomerase.
 The reaction is freely reversible at normal cellular concentrations
of the two hexose phosphates and thus catalyzes this
interconversion during both glycolysis and gluconeogenesis.

Page 15 of 86
IV. 6-Phosphofructo-1-Kinase (Phosphofructokinase-1, PFK-1)
reaction
 Phosphofructokinase-1 catalyses the use of a second ATP to
convert F6P to fructose 1,6-bisphosphate (F1,6BP).
 The reaction is metabolically irreversible because of large positive
free energy in the reverse direction.
 PFK-1 is considered to be the rate-limiting enzyme of
glycolysis

V. Aldolase
 Aldolase catalyses the hydrolysis of F1,6BP into two 3-carbon
products: dihydroxyacetone phosphate (DHAP) and
glyceraldehyde 3-phosphate (G3P).
 The reaction proceeds readily reversible, being utilized for both
glycolysis and gluconeogenesis.

VI. Triose Phosphate Isomerase

 Triose Phosphate Isomerase catalyzes the interconversion of
glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.
 Only G-3-P continues along the glycolytic pathway.
 This reaction thus permits both products of the aldolase reaction to
continue in the glycolytic pathway
 This reaction marks the end of the first phase of glycolysis.
VII. Glyceraldehyde-3-Phosphate Dehydrogenase (G3PDH)
reaction
 This reaction marks the beginning of the second phase of glycolysis.
 This phase features the energy-yielding glycolytic reactions
thatproduce ATP and NADH.
 The first of these reactions is the NAD+ dependent oxidation of
G3P to 1,3-bisphosphoglycerate (1,3BPG) and NADH catalyzed
by glyceraldehyde-3-P dehydrogenase (G3PDH).
 The reaction is reversible
Page 16 of 86
VIII. Phosphoglycerate Kinase
 The high-energy phosphate of 1,3-BPG is used to form ATP and
3-phosphoglycerate (3PG) by the enzyme phosphoglycerate
kinase.
 Note that this is the only reaction of glycolysis or
gluconeogenesis that involves ATP and yet is reversible under
normal cell conditions.
 Since the phosphate group comes from a substrate molecule, called
substrate level phosphorylation
 This is the first ATP-generating step of glycolysis.

Page 17 of 86
IX. Phosphoglycerate Mutase reaction
 The remaining reactions of glycolysis are aimed at converting the
relatively low energy phosphoacyl-ester of 3PG to a high-
energy form and harvesting the phosphate as ATP.
 The 3PG is first converted to 2PG by phosphoglycerate mutase (a
mutase is an isomerase enzyme).
X. Enolase
 2PG is dehydrated to phosphoenoylpyruvate (PEP), a high energy
intermediate.
XI. Pyruvate Kinase
 The final reaction in glycolysis is catalyzed by the highly
regulated enzyme pyruvate kinase (PK). In this strongly exergonic
reaction, the high-energy phosphate of PEP is conserved as
ATP.
 Second ATP –generating step - substrate level phosphorylation.
 Pyruvate is also produced in this reaction
 Reaction is metabolically irreversible.

Page 18 of 86
 1

5
6

10

Schematic representation of glycolysis

Page 19 of 86
2.6.2 Metabolic fate of pyruvate
The fate of pyruvate produced in glycolysis depends on the metabolic state
of the cell.
Under anaerobic conditions, cells must be able to regenerate NAD+,
coenzyme reduced to NADH in glycolysis. Failure to regenerate NAD+would

make glycolysis to stop.

NADHcarries electrons to the electron transport system where it is oxidized

to NAD+ and thus regenerated during oxidative phosphorylation. The
process requires oxygen as the final electron acceptor.
The following are the metabolic fates of pyruvate under different physiologic
conditions
(i) Oxidation to Acetyl-CoA
Under aerobic conditions, pyruvate is oxidatively decarboxylatedto form
acetyl-CoA in the mitochondria. The reaction is catalyzed the pyruvate
dehydrogenase complex (PDH). The acetyl-CoA is a key molecule in
metabolism. Co-A (Co-enzyme A) is derived from the B vitamin
pantothenic acid
There are 2 anaerobic pathways that use NADH and regenerate NAD+.

(ii) Alcoholic fermentation – pyruvate is converted to ethanol in

anaerobic microorganisms. The process is used to produce alcoholic
beverages.

H+ CO2 NADH NAD+

pyruvate acetaldehyde ethanol
pyruvate alcohol
decarboxylase dehydrogenase

glucose +2Pi+ 2ADP + 2H+ ---> 2 ethanol + 2CO2 + 2ATP + 2H2O

Page 20 of 86
 (iii) Lactate fermentation -
In limited oxygen or anaerobic conditions pyruvate is reduced to lactic
acid. The reaction is catalyzed by lactate dehydrogenase enzyme
(LDH). Accumulation of lactic acid cause muscle fatigue
NADH + H+ NAD+
pyruvate ------------------------> lactate
lactate
dehydrogenase

NB: Lactate is also produced by bacterial fermentation of lactose e.g. during

processing of fermented milk products e.g. yoghurt and mala.

2.6.3 Importance of glycolysis

 provides the mitochondria with pyruvate for use in the TCA cycle
 Provides dihydroxyacetone phosphate which can be converted to
glycerol-3-phosphate for use in lipogenesis (to make triglycerides)
 Energy production
 Glycolysis only generates 2 ATP molecules from each glucose
molecule. This is only 5 % of the amount of energy (38 ATP) that
can be generated from complete oxidation of glucose molecule
through the TCA cycle
 However, glycolysis is important during intense muscular exercise
where oxygen supply is often insufficient to meet the demands of
aerobic metabolism. the rate of ATP production from glycolysis
is approximately 100X faster than from oxidative
phosphorylation
 Glycolysis provides all the energy required by the red blood cells
since they lack mitochondria to carry out oxidative
phosphorylation.

Page 21 of 86
2.7 Regulation of carbohydrate metabolism (Glycolysis)
 The reactions catalyzed by hexokinase, PFK-1 and PK all proceed
with a relatively large free energy decrease. All three enzymes are
allosterically controlled.
 The rate limiting step in glycolysis is the reaction catalyzed by PFK-
1.
o ATP is both a substrate and an allosteric inhibitor of
PFK-1.
 The most important allosteric regulator of both glycolysis and
gluconeogenesis is fructose 2,6-bisphosphate.

There are three enzymes that can be regulated:

1) hexokinase
o Catalyzes the first irreversible reaction.
o Inhibited by glucose 6-phosphate.
2) phosphofructokinase-1
o ATP is an allosteric inhibitor.
o AMP is an allosteric activator; same for ADP
 When [ATP] is low, [AMP] is high → the PFK-1 is stimulated
o Citrate is an allosteric inhibitor of PFK-1 (ample substrate entering citric
acid cycle).
o pHialso regulates PFK-1 ( inhibition is due to excess H + due to lactic acid
accumulation – excesss H+ indicates that there is no O 2 present to
continue).
o Fructose 2,6-bisphosphate is an allosteric activator.

3) Pyruvate kinase
o Regulated by allosteric modulation and covalent modification.
o Allosterically activated by fructose 1,6-bisphosphate.
o Allosterically inhibited by [ATP].

Page 22 of 86
Page 23 of 86
Regulation of Blood Glucose Levels
 One of the most important functions of the liver is to produce glucose
for the circulation.
 Both elevated and reduced levels of blood glucose trigger hormonal
responses to initiate pathways designed to restore glucose homeostasis.
Low blood glucose triggers release of glucagon from pancreatic α-cells.
High blood glucose triggers release of insulin from pancreatic β-cells.

Hormonal Control of Blood glucose level

Hormone Mechanism Action on blood
glucose level
Insulin Enhances glucose uptake by muscles, Reduction
synthesis of glycogen, synthesis of
triglycerides by adipose tissue
Glucagon Enhances breakdown of glycogen to Increase
glucose in the liver, release of fatty acids
from adipose tissue
Adrenalin Enhances glycogen breakdown to glucose Increase
(epinephrine (liver) and to lactic acid (muscles)
)

2.8 Gluconeogenesis
 Gluconeogenesis (GNG) is a metabolic pathway that results in the
synthesis of glucose from non-carbohydrate carbon substrates such as
lactate, glycerol, and glucogenic amino acids.
 It takes place mainly in the liver and, to a smaller extent kidney cortex.
 It occurs during periods of fasting, starvation, or intense exercise
and is highly endergonic.
 GNG is often associated with ketosis.
 It is a target of chemical therapy for type II diabetes, such as metformin,
which inhibit glucose formation and stimulate glucose uptake by cells
Page 24 of 86
 Several non-carbohydrate carbonsubstrates can enter the GNG pathway.
A common substrate is lactic acid, formed during anaerobic respiration in
skeletal muscle. Lactate may also come from red blood cells, which obtain
energy solely from glycolysis as they have no mitochondria for aerobic
respiration.
 Lactate is transported back to the liver where it is converted intopyruvate
using lactate dehydrogenase (LDH).
 Pyruvate is the first designated substrate of the GNG pathway.
 All citric acid cycle intermediates (after conversion to oxaloacetate),
amino acids other than lysine or leucine, and glycerol can also function as
substrates for GNG.
 Amino acids must first have their amino group removed by
transamination or deamination before entering the GNG cycle directly (as
pyruvate or oxaloacetate), or indirectly via the citric acid cycle.
Steps in Gluconeogenesis pathway
 GNG consists of eleven enzyme-catalyzed reactions.
 It can begin in the mitochondria or cytoplasm, depending on the
substrate being used.
 Seven of the reactions are reversible steps found in glycolysis.
 In the mitochondria, GNG begins with the formation of oxaloacetate
through carboxylation of pyruvate at the expense of one molecule of ATP.
o This reaction is catalyzed by pyruvate carboxylase, which is stimulated
by high levels of acetyl-CoA (when fatty acid oxidation is high in the liver)
and inhibited by high levels of ADP.
 Oxaloacetate must then be reduced into malate using NADH in order to
be transported out of the mitochondria.
o In the cytoplasm, malate is oxidized back to oxaloacetate using NAD+,
where the remaining steps of gluconeogenesis occur.
 Oxaloacetate is then decarboxylated and phosphorylated to produce
phosphoenolpyruvate (PEP) by phosphoenolpyruvate carboxykinase. One
molecule of GTP is hydrolyzed to GDP in the course of this reaction.

Page 25 of 86
 The next steps in the reaction are the same as reversed glycolysis.
However, fructose-1,6-bisphosphatase(F1,6BPase) converts fructose-1,6-
bisphosphate(F1,6BP) to fructose-6-phosphate(F6P).
o The purpose of this reaction is to overcome the large negative
ΔG.
o F-1,6-BPase is considered to be the rate-limiting enzyme in GNG.
 Glucose-6-phosphate (G-6P) is formed from fructose-6-phosphate by
phosphoglucoisomerase.
o G-6P can then be used in other metabolic pathways or dephosphorylated
to free glucose.
o Nb. Whereas free glucose can easily diffuse in and out of the cell, the
phosphorylated form (G-6P) is "locked" in the cell. The cell uses this
mechanism as a way to control intracellular glucose levels.
o The final reaction of GNG is the formation of glucose. It is carried out in
the lumen of the endoplasmic reticulum. G-6P is hydrolyzed by glucose-6-
phosphatase to produce glucose. Glucose is then shuttled into the cytosol
by glucose transporters located in the membrane of the endoplasmic
reticulum.
o Synthesis of glucose from three and four carbon precursors is essentially
a reversal of glycolysis.
Gluconeogenesis pathway is summarized below

Page 26 of 86
 11

10

Reaction pathway for gluconeogenesis. The enzymes that

are not indicated are the ones that catalyze the same
reactions in glycolysis.
Glycolysis and Gluconeogenesis pathways are both spontaneous. If
both pathways were simultaneously active within a cell it would constitute a
"futile cycle" that would waste energy. Overall, each pathway may be
summarized as follows (ignoring water & protons):
Page 27 of 86
Glycolysis
glucose + 2 NAD+ + 2 ADP + 2 Pi → 2 pyruvate + 2 NADH + 2 ATP
Gluconeogenesis
2 pyruvate + 2 NADH + 4 ATP + 2 GTP → glucose + 2 NAD+ + 4 ADP +
2 GDP + 6 Pi
2.7.1 Citric acid cycle
 The citric acid cycle is also known as tricarboxylic acid cycle (TCA) or
Krebs cycle.
 It is the third step in carbohydrate metabolism.
 After the glycolysis takes place in the cell's cytoplasm, the
pyruvate molecules travel into the interior of the mitochondrion.
 Once the pyruvate is inside the mitochondria, carbon dioxide is
enzymatically removed from each three-carbon pyruvate molecule
to form acetate.
 Acetate combines with an enzyme, coenzyme A, to produce
acetyl coenzyme A, also known as acetyl CoA.
 Once acetyl CoA is formed, the citric acid cycle begins. The cycle is
split into eight steps as outlined below.
Step 1
 The acetate subunit of acetyl CoA is combined with oxaloacetate
to form a molecule of citrate.
 The acetyl coenzyme A acts only as a transporter of acetate from one
enzyme to another. After Step 1, the coenzyme is released by hydrolysis
so that it may combine with another acetate molecule to begin the Krebs
cycle again.

Page 28 of 86
 The TCA cycle

Step 2
 The citrate molecule undergoes an isomerization. A hydroxyl
group and a hydrogen atom are removed from the citrate structure in the
form of water.
 The two carbons form a double bond until the water molecule is added
[Link] now, the hydroxyl group and hydrogen molecule are reversed
with respect to the original structure of the citrate [Link],
isocitrate is formed.
Step 3
 The isocitrate molecule is oxidized by a NAD+ molecule. The NAD+
molecule is reduced by the hydrogen atom and the hydoxyl group.
 The NAD+ binds with a hydrogen atom and carries off the other
hydrogen atom leaving a carbonyl group. This structure is very unstable,
so a molecule of CO2 is released creating alpha-ketoglutarate.
Step 4
Page 29 of 86
 Coenzyme A oxidizes the alpha-ketoglutarate molecule . A molecule of
NAD+ is reduced again to form NADH and leaves with another hydrogen.
 This instability causes a carbonyl group to be released as carbon
dioxide and a thioester bond is formed in its place between the
former alpha-ketoglutarate and coenzyme A to create a molecule of
succinyl-coenzyme A complex.
Step 5
 A water molecule sheds its hydrogen atoms to coenzyme A. Then, a
free-floating phosphate group displaces coenzyme A and forms a bond
with the succinyl complex.
 The phosphate is then transferred to a molecule of GDP to produce an
energy molecule of GTP. It leaves behind a molecule of succinate.
Step 6
 Succinate is oxidized by a molecule of FAD (Flavin adenine
dinucleotide). The FAD removes two hydrogen atoms from the succinate
and forces a double bond to form between the two carbon atoms, thus
creating fumarate.
Step 7
 Fumarase enzyme adds water to the fumarate molecule to form
malate. The malate is created by adding one hydrogen atom to a carbon
atom and then adding a hydroxyl group to a carbon next to a terminal
carbonyl group.
Step 8
 Final step, the malate molecule is oxidized by a NAD + molecule.
The carbon that carried the hydroxyl group is now converted into a
carbonyl group. The end product is oxaloacetate which can then
combine with acetyl-coenzyme A and begin the Krebs cycle all over again.

Summary
In summary, three major events occur during the Krebs cycle.
 OneGTP (guanosine triphosphate) is produced which eventually
donates a phosphate group to ADP to form one ATP;
Page 30 of 86
  three molecules of NAD+ are reduced;
 One molecule of FAD is reduced.
o NB. Although one molecule of GTP leads to the production of one
ATP, the production of the reduced NAD + and FAD are far
more significant in the cell's energy-generating process.
This is because NADH and FADH 2 donate their electrons to an
electron transport system that generates large amounts of
energy by forming many molecules of ATP.
Products
Products of the one turn of the cycle are: one GTP (or ATP), three NADH,
one FADH2, and two CO2.
Nb. Because two acetyl-CoA molecules are produced from each
glucose molecule, two cycles are required per glucose molecule.
Therefore, at the end of both cycles, the products are: two GTP, six NADH,
two FADH2, and four CO2

2.9 Metabolic disorders of carbohydrate metabolism

1. Galactosemia
A series of rection is necessary to convert galactose into phosphorylated
form of glucose that can be used in cellular metabolic reactions. In
humans, the genetic disease galactocemia is caused by the absence of
one or more of the enzymes needed for these convulsions. A toxic
compound formed from galactose accumulates in people who suffer from
galactocemia. If the condition is not treated, galactosemia leads to a
severe mental retardation cataract and early death.
However the effect of these disease can be avoided entirely by providing
galactosemic infants with a diet that does not contain galactose. Such a
diet cannot contain lactose and therefore must contain no milk or milk
product.
2. Lactose intolerance
Many adult and some children are unable to hydrolise lactose because
they do not make the enzyme lactase. This is known as lactose

Page 31 of 86
 intolerance. Undigested lactose remain in the digestive tract and cause
cramping and diarrhea that can eventually lead to dehydration.
3. Diabetes mellitus
This is a metabolic disease due to absolute or relative insulin deficiency.
Insulin deficiency can lead to increased blood glucose levels. Inspite of
this high glucose level in the blood, the ntry of glucose into the cell is
inefficient hence all cells re starved for glucose.

Self-Test Questions
1. Define Glycolysis and Gluconeogenesis. What are the inputs and
outputs of each of the pathways?
2. If both pathways were simultaneously active within a cell it would
constitute a "futile cycle" that would waste energy. How does the
cell prevent this?
3. Differentiate between aerobic and anaerobic glycolysis.
4. Explain the role of insulin and glucagon in control of blood glucose
5. GNG is associated with ketosis. Explain.
6. Explain the three metabolic fates of pyruvate in living organisms.
7. Explain the role of Krebs cycle in energy generation?
8. Define oxidative phosphorylation.
9. Write an equation summarizing the Krebs cycle.

Page 32 of 86
UNIT 3: LIPIDS
Unit objectives
By the end of the unit, the learner should be able to;
1. Define and name the classification of lipids
2. State the various structures of lipids and give their nomenclature
3. Discuss the different derivatives of lipids
4. Explain the metabolism of lipids
5. Outline the significant of cholesterol in health
6. Highlight the functions if lipids

 Lipids are groups of organic molecules of varying chemical composition

that are insoluble in organic solvents e.g. ether. They are fatty acids and
their derivatives, and substances related biosynthetically or functionally
to these compounds
 Lipids are organic compounds that are readily soluble in non-polar solvent
([Link]) but not in polar solvent (e.g. water).
Examples of lipids are waxes, oils, sterols, cholesterol, fat-soluble vitamins,
monoglycerides, diglycerides, triglycerides (fats), and phospholipids.

3.1 Functions of lipids

i. Component of the cells membranes: Phosphoglycerides, sphingolipids
and steroids make up the basic structure of all cell membranes which
control the flow of molecules in and out of thecells.
ii. Source of energy: when oxidized each gram of fat releases 9kcal of
energy, more than twice theenergy released by oxidation of one gram of
carbohydrate or protein.
iii. Energy storage: Most of the energy stored in the body is in form of lipids
(triglycerides) storedin fat cells called adipocytes.
iv. Synthesis of other compounds such as Hormones (e.g. steroid
hormones), bile, and vit D.
v. Carriers of fat soluble vitamin A, D, E and K.

Page 33 of 86
vi. Cushioning of vital organs: serve as shock absorbers (fat pads inside the
body cavity)
vii. Protect body from temperature extremes – subcutaneous fat layer under
the skin acts as an insulator

3.2 Building blocks of lipids

These are fatty acids
They are long hydrocarbons containing a carboxylic group at one end
The chain length ranges from 4-6 carbon atoms 12-24 being the most
common fatty acid will always contain an even number of carbon atoms
The numbering will start from carboxylic functional group at physiological PH
the carboxylic group is greatly ions and therefore fatty acid is referred to as
according to their carboxylic group saturated fatty acids have carbon single
bond while unsaturated have at least a double bond in their structure.
Saturated fatty acids of less than 8 carbon atoms are liquid at room
temperature where as those containing more than ten are solid the presence
of a double bond in a fatty acid will significantly lower the melting point.
Majority of fatty acids are acquired in the diet but the body synthetic
machinery can also be able to synthesize some the fatty acids which the
body cannot synthesize are known as essential while the ones that the body
can synthesize are known as non-essential

3.3 Classification of lipids

Simple lipids and complex lipids
Simple lipids and ester of fatty acids with an alcohol backbone
Complex lipids are ester of fatty acids with alcohol backbone and other
groups e.g. protein phospholipids phosphorus
Classification of simple and complex is based on the structure another
classification is based on reaction these are saponifiable and non-
saponifiable

Page 34 of 86
Saponification is the reaction of a lipid with a base to form a soap are known
as saponifiable and they must have an ester bond linkage e.g. phospholipids
and acylglyceral
Non-saponifiable lipids are unable to react with bases to form soap and they
are known as cholestral
Examples of simple lipids the alcohol group in simple lipids in most cases and
glycerol the first group of simple lipids are neutral lipids they include
acylglycerol and waxes
Acylglycerol are formed by esterification of fatty acids to a glycerol backbone
and the esterified fatty acids is known as acyl group acylglyrerols are found
in adipose tissues
Mono acylglycerol consist of one acylgroup esterified to a glycerol backbone
die as a glycerol backbone
Priacylglycerol consist of three acyl groups esterified to 3 hydroxyl groups of
glycerol neutral fats exists especially as trigacylglycerol .Mono and di are
only formed during hydrolysis of TAG in the adipose tissue

3.3.1 Waxes
They are ester of long chain fatty acids and long chain alcohol
They form natural proteins on fruits leaves feathers and skin fur
These coatings have a protective function

3.3.2 Complex lipids

These are esters of fatty acids and alcohol and other groups such as;
i. Phospholipids
They are also known as phosphoglycerides or acrylics phosphoglycerides
They are the major component of the cell membrane they form a bilayor
structure of the cell membrane
ii. Glycerol based phospholipids
They have glycerol as thus alcohol group basic structure
The basic structure of these phospholipids is known as phosphatidate

Page 35 of 86
Phosphatidase is a key precursor in the brosynthesis of phosphaglycerides
one can esterify serine or ethanolamine or choline

Page 36 of 86
a. To a phosphatidate to generate a complete phosphoglyceride
When you esterify ethernal amino to a phosphotidate you get
phosphatidyletha nolamine /cephaline.
They occur in tissues especially in the cell membrane where they form a
lipid bilayer
b. Phosphotidylcholine/lecithin
They are found in the cell membrane and they facilitate the combination
of lipids with proteins from lipoproteins.
Phosphotidycerine are also found in the cell membrane that forms the bi-
layer.
iii. Sphingosine based phospholipids
They have the sphingosine as the alcohol moiety (group).
The acyl groups in sphingosne are attached to amide rather than ester
link. The only phosphate derivatives for sphingosine are the
sphingomyelin
Sphingomyelin contain a choline as the amino alcohol and are found in
the plasma membrane .and in the complex membrane of the nerves.
iv. Lipoprotein commonly occur in the membrane of
mitochondria,endoplasmic,reticulum,nucleus,myelin sheath of
nerves ,chloroplast ,bacterial membranes .lipid components
[Link], phospholipids and cholesterol are joined to
[Link] consisting of non-polar amino-acids e.g. lipovitelline
which is a lipoprotein found in the egg yolk .
v. Lipopolysacharides
Are highly complex compounds which are present in the surface
layer of [Link] &gram bacteria.
They are organized in the outer layer and the peripheral parts of the
Lipopolysacharides containing antigenic
To form high molecular weight polysaccharides
vi. Proteolipids
Page 37 of 86
 The brain tissues contain protein, lipid complex called
proteolipids which are insoluble in water but soluble in organic
solvents.
The protein portion in this lipid has a high content of hydrophobic
amino acid while the lipid portion is made up of equal parts of
phosphoglyceride and cerebrocytes.]

3.3.3 Lipid derivatives

They are derivates of either complex of simple lipids obtained after
hydrolysis of simple and complex lipids.

The most common derived lipids are steroids, all steroids have common
cyclic nucleus known as cyclopentane per hydrophenathrene.
Steroids are physically important since some of them function asbi-acid, sex
hormones and adrinocorticlerid hormones.
Some steroids contain an alcoholic group of carbon 3 under side chain of 8-
10 carbons at carbon 17 are called sterol.
The best known examples that are widely distributed in animal and plant
tissues are ergosterol, respectively .cholesterol is most abundant an rain,
nervous tissues, adrenos and the [Link] is found in yeast, mold and
it’s a precursor of vitamin D

I. Cholesterol
It is a sterol with a molecular formulae of C27H45OH,it has OH at carbon no
3 and has saturated double bond between carbon 5 and carbon 6and 2
methyl groups at carbon 3.
It has 8 carbon side chain attached to carbon no 17
Cholesterol occurs both in freeform and ester form in which it is esterfeid
with tatty acids at the OH in carbon 3
Functions of cholesterol
i. It serves as the component of a cell membrane fluidity
ii. It is a precursor of steroid hormones
Page 38 of 86
iii. It is involved in storage and transport, mainly done by cholesterol
esters.

Significance of cholesterol in health

Associated with atherosclerosis which is a deposition of cholesterol and other
lipids an inner wall of the larger arteries and these deposits are called plaque
walls.
Accommodation of plaque causes the arteries passage to become
progressively narrower thus the walls of the arteries also loose their
elasticity and ability to expand and accumulate the volume of blood by the
heart.
The blood pressure increases as the work to pump sufficient blood through
the narrow passage which eventually leads to hypertension, the build up of
plaque also causes the inner walls to have a rough surface rather than a
normal surface and this is referred to as coronary thrombosis.
II. Saponificaton
When fats are boiled in alkali thy form soaps which is Na or K salts. This
process of soap formation is called saponification which is expressed as
milligram of NaOH required to saponify 1g of salt.
Soaps when dissolved in water form an emulsification and produce micelle
which is stable arrangements having polar heads directed outwards & non-
polar ends towards the interior.
In water these substances exist as sodium ion and pulmitate ions. The
sodium ion is an ordinary hydrated metal ion. The cleansing property must
then be centraled in the pulmitate ion.
The hydrophobic end is polar negatively charged carbohydrate group. The
hydrophobic end is a long hydrocarbon group which is soluble in oil and
grease but not in water. When soap comes into contact with grease or soil
surface the hydrocarbon end of the soap dissolves in the grease ,leaving the
negatively charged carbohydrate and expose on the grease surface.

Page 39 of 86
Because the negatively charged group because they are strongly attracted
to water, small droplets are formed and the grease is literally lifted or floated
away on the soiled object.
The densing property of soap is due to its ability to act as an emulsifying
agent between water and water soluble greases &oils.

Page 40 of 86
 III. Rancidity
Rancidity of lipids
Fats develop unpleasant odour /smell or taste when exposed to air
This is because the fats turned rancid due to action of lights heat and
bacteria action.
Rancid fat is unsuitable for human consumption because besides having
unpleasant smell and taste it oxidizes essential dietary constituent and gives
rise to peroxide linkages with double bonds
IV. Hydrogenation
The double bond of unsaturated fatty acids can be readily oxidized or
halogens may be added to them.
Addition of hydrogen to double bonds processed in the presence of platinum
and nickel. And the process is known as hydrogenation

3.4 Fat metabolism

Triglycerides are highly hydrophobic, must be processed before thy can be
digested, absorbed and metabolized, in the small intestine, lipases are not
very efficient
In fact most dietary fat arrive in the duodenum and form fat globules which
stimulate the secretion of bile from the gallbladder .bile and composed of
mecyles of leathin ,cholesterol, protein ,bile salts ,inorganic &bile pigments.
Micelles are aggregation of molecules having a polar region and non-polar
region .non-polar ends of bile salts tend to bunch together when placed in
water. Where as the hydrophobic and interact with water. Bile salts are made
in the liver and stored in the gall bladder awaiting the stimulus lobe secreted
in the duodenum. The major bile salts include:
i. Cholet
ii. Chenodeoxycholated
After a meal is eaten, bile floats through a common bile duct into tiny
droplets increasing the surface area of the lipid molecules allowing them to
be more easily hydrolyzed by the lipases.
Page 41 of 86
These droplets are in form of triglycerides or trialyglycerids which are fatty
esters of glycerols.a protein calipase binds to the surface of the lipids
droplets and helps pancreatic lipase to stick to the surface and hydrolyze the
ester bond between he glycerol and fatty acids of the triglycerides.
In this process two of the three fatty acids are produced and the
monoglycerids and the three fatty acids produced .mix freely with the
meciles of the bile.
These are readily absorbed through the membranes of epithelial intestinal
cells.
The monoglycerides and the fatty acids are then re-assembled into
triglycerides that are combined with protein to produce the class plasma
lipoprotein called chylomicrons.
These collections of lipids and proteins are secreted into small lymphatic
vessels and eventually arrive in the blood stream .once in the blood stream;
the triglycerides are once again hydrolyzed to produce glycerol and fatty
acids that are then absorbed by the cells.
If the body needs energy, these molecules are degraded to produce ATP. If
the body does not need energy these energy rich molecules are stored

3.5 Storage
They are stored in form of triacylglycerides in the form of fat droplets in the
cytoplasm of the deposits; contain a large fat droplet that accounts for nearly
the entire volume of the cell.

Page 42 of 86
UNIT 4: PROTEINS
Unit: Objectives
By the end of this lesson, the learner should be able to:
1. Classification of amino acids
2. Explain the structures of proteins
3. Explain the denaturation of proteins
4. Explain the metabolism of proteins
5. Disorders of protein metabolism

Amino acids are the building blocks of proteins. Each amino acid contain an
R group it is also charges, shape and hydrogen bonding capacity. We have
twenty different types of amino acids in a protein.

4.1 Classification of amino acids.

1. The most common classification is based on polarity of the R group.
Polarity is the tendency of a molecule to react with water. They are
grouped as polar and non polar. The ones that have high tendency to
water are known as polar, they have hydrophilic R group. They are soluble
in water. This is because these amino acids contain functional group that
forms hydrogen bond with water. They consist of serine, threonine,
cysteine, glutamine, asparagines and tyrosine
Non polar amino acids. They are hydrophobic and they never interact with
water. The R group of these amino acids are hydrophobic hence they
cannot dissolve in water. They include alanine, leusine, isoleusine, valine,
phenylananine, tryptophan, methionine, proline and glycine.

2. Amino acid with negatively charged R group. They have net negative
charge at physiological pH and are also reffered to as acidic amino acid.
They include glutamate/glutamic acid and also aspartate also known as
aspartic acid.

Page 43 of 86
Amino acid with positively charged R group. They have a net positive
charged at neutral pH and also referred to as basic amino acid. They
include lysine, arginine and histidine.

3. Amino acid can also be classified as essential and non-essential.

Essential amino acid cannot be synthesis in the body and hence must
be taken in the diet. They include valine, leusine, isoleusine,
phenylalanine, threonine, tryptophan, methionine, lysine and histidine.
Non essential amino acids can be synthesized by the body.

4.2 Structures of amino acids

Name of
Abbreviatio
Amino Structure of R group Polarity
n
Acid

Neutral
Alanine Ala
Non-polar

Basic
Arginine Arg
Polar

Neutral
Asparagine Asn
Polar

Aspartic Acidic
Asp
Acid/Aspartate Polar

Neutral
Cysteine Cys Slightly
Polar

Page 44 of 86
Glutamic Acidic
Glu
Acid/Glutamate Polar

Neutral
Glutamine Gln
Polar

Neutral
Glycine Gly
Non-polar

Basic
Histidine His
Polar

Neutral
Isoleucine Ile
Non-polar

Neutral
Leucine Leu
Non-polar

Basic
Lysine Lys
Polar

Neutral
Methionine Met
Non-polar

Neutral
Phenylalanine Phe
Non-polar

Neutral
Proline Pro
Non-polar

Page 45 of 86
 Neutral
Serine Ser
Polar

Neutral
Threonine Thr
Polar

Neutral
Tryptophan Trp Slightly
polar

Neutral
Tyrosine Tyr
Polar

Neutral
Valine Val
Non-polar

4.3 Properties of amino acids

1. They show stereoisomerism. They show D and L configuration. The
most active amino acids will have L-configuration and they are neutral.
2. Ionization( they can donate or accept a proton from water)
Ionization is an aspect where a molecule obtain a charge. Amino acid
can be ionized at different pH because they have two ionizing groups
that is carboxylic group( COOH) and amino group( NH 2) which can be
ionized to COO- and NH+3 . When they have zero charged they are
electrically neutral and are known as zwitterions.
Ionization property is important in the separation using a technique
known as ion exchange chromatography.
3. Acid base property

Page 46 of 86
 An acid is a proton donor while a base is proton acceptor. Amino acid
at neutral pH can act as a base or an acid depending on the medium
they are in. Amino acid in this dual properties are said to be
amphoteric, they have both acidic and basic properties.
As an acid:
The -NH3+ group is a weak acid and donates a hydrogen ion to a water
molecule. Because it is only a weak acid, the position of equilibrium will lie to
the left.

As a base:
The -COO- group is a weak base and takes a hydrogen ion from a water
molecule. Again, the equilibrium lies to the left.

4.4 Peptides
They are polymers of amino acid. The amino acids are linked together by
peptide bond. The bond is formed by dehydration between the amino group
of one amino acid and a carboxylic group of another amino acid. The end
with a free amino group is called N terminal while the other is called
carboxylic terminal.
When we join several amino acids we get something known as polypeptide
e.g. protein

Page 47 of 86
N-terminus C-terminus
The C-terminus (carboxyl-terminus) of a polypeptide is the end of the
amino acid chain terminated by a free carboxyl group (-COOH) while the N-
terminus (amino-terminus) refers to the start of a polypeptide terminated
by an amino acid with a free amine group (-NH2). The convention for writing
peptide sequences is to put the N-terminus on the left and write the
sequence from N- to C-terminus.

4.5 Structure and functions of protein

Page 48 of 86
Protein is polymers of amino acids linked by peptide bonds in a linear
sequence specified by the DNA.
4.5.1 Functions of protein
1. They act as enzymes which are catalyst that speeds up the
biochemical reactions in the system.
2. They have transport and storage function e.g. some proteins bind
other molecules for the purpose of transport and storage e.g.
lipoprotein and haemoglobin.
3. They offer mechanical support and shape e.g. structural proteins which
provide mechanical support in the cells and tissues e.g. collagen
4. They are involved in coordinated motion. Assemblies of proteins can do
mechanical work e.g. motion i.e. contraction and relaxation of muscle,
protein enables one to move from one place to another.
5. Some proteins act as hormones which regulate biochemical activities
in the target cells or tissues e.g. insulin which is involved in the
glycogen metabolism.
6. They offer protection i.e. the skin, hair, nail.
4.6 Classification of protein
There are three common classifications systems in use:
i. Classification by function
All proteins with similar biological functions are classified together e.g.
o Catalytic proteins which catalyze biochemical reactions and are
called enzymes.
o Transport proteins which circulate, bind and transport other
molecules in the cells and in the blood e.g. hemoglobin.
o Regulatory proteins, which are chemical messengers that help
regulate physiological processes e.g. hormones.
o Defense proteins, which protect the body disease e.g.
immunoglobins.
o Storage proteins which contain nutrients for an organism e.g. ferritin
and casein.

Page 49 of 86
 o Structural proteins which provide mechanical support especially in
bones, skin hair e.t.c

ii. Classification by shape into two:

o Fibrous protein, which are water insoluble and are mainly found in
the hair, skin connective and elastic tissue. They are string like and can
intertwine to form strong fibers.
o Globular protein, are water soluble and forms stable suspensions.
These include enzymes, blood proteins and immunoglobins.

[Link] by Composition
Proteins can be simplified as either:
o Simple protein which is made up of only amino acids residues.
o Conjugated protein which has other chemical components in
addition to amino acids incorporated in it. These may be organic or
inorganic prosthetic groups (heme units, lipid molecule, carbohydrate or
metal ion. e.g.

A. Glycoproteins
o conjugated proteins that contain carbohydrates or carbohydrate
derivative in addition to amino acid.
o include, collagen that forms the bones and teeth and also as structural
material in tendons, ligaments and blood vessels and; immunoglobins
which are antibodies that protect the body from invasion by
microorganisms or foreign molecules.
B. Lipoproteins
o are conjugated proteins that are composed of both lipids and amino
acids. They help suspend and transport lipids through the blood
stream. The lipids are insoluble in the blood which is an aqueous
medium. Lipoproteins are further classified according to their density
i.e. fraction of protein and lipid present in them.
 Very Low Density Lipoprotein (VLDL)
Page 50 of 86
 o are the main carriers of triglycerides in the blood stream. They
provide the cells with lipids as required and their density
increase and they become Low Density Lipoproteins (LDL).
 Low Density Lipoproteins (LDL)
o Carry cholesterolto the cells for their use. LDL levels
correlate very well with heart diseases. It is sometimes
referred to as ‘bad cholesterol’.
 High Density Lipoproteins (HDL)
o These transport cholesterol away from the cells to the liver
for processing and excretion from the body. HDL levels
correlates inversely with heart disease risk. They are
sometimes called “good cholesterol”.
Nb. Reduction in levels of LDL cholesterol levels is the goal of dietary
management in slowing down the advance of atherosclerosis. Reduction in
the consumption of saturated fats which stimulate cholesterol
synthesis is the key action. High levels of HDL are desirable because it is an
efficient means of removing excess cholesterol by the body which would
otherwise deposit within the circulatory system. Generally, women have
higher levels of HDL than men and smokers have uniformly lower levels of
HDL than non-smokers.
o Exercise on a regular basis e.g. brisk walking tends to increase HDL levels.
o Genetic predisposition may also play a role in the establishing HDL
levels.

4.7 Properties of proteins

1. Solubility-most protein will vary in their solubility with globular proteins
being more soluble than the fibrous protein
Solubility in aqueous solvent is enhance by weak ionic interactions including
hydrogen bonds between solute molecules and water
Solubility of the protein is influenced by

Page 51 of 86
 a. Salt concentration-addition of small amounts of neutral salts to a
protein will increase its solubility add salt will increase the ionization of
AA side chains this increases interactions between protein solute and
the solvent result in increase solubility. This phenomenal is known as
salting in a protein enhancing of a protein ionization (soluble as a
result of salt addition it depends principally on the ionic strength
however with increased salt concentration solubility decreases this is
because at high salt concentration the abundance of interaction
between the added ions and water decreases the possibilities of
protein water interaction this results to increase to protein interaction
decreasing the solubility leading to protein precipitation and this
phenomenal is known as salting out of a protein
b. PH –it will also influence protein solubility under extreme PH the
pattern of charged ionic able side chain changes to cause an extraction
of the tertiary structure of the protein leading to protein denaturation
this exposes the hydrophobic side group of AA to the aqueous
environment decreasing the solubility considerable solubility also
decreases at is-electric point (where the PH at which a protein /AA is
electrically neutral)in the absence of a net charge there is no repulsion
between the protein molecules to prevent the formation of an insoluble
aggregates
c. Temperature-the solubility will increase with temperature up to
between 400-500c and above this thermal agitation tends to disrupt the
tertiary structure leading to denaturation with a concomitant decrease
in solubility
2. Acid, Base properties
A protein will usually have charged group i.e. the amino.s carboxyl terminal
ends as well as some side groups. This group will contribute to the acid base
properties at low PH there are more positively charged group than negatively
charged group In this case the protein is cataonic and will migrate towards
the cathode in an electric field at high PH negatively charged group
predominate and the protein is anionic isolectic PH there will be equal
Page 52 of 86
number of +ve and –ve charges I a protein therefore the protein will remain
immobile in the electric field. This charged property is important in protein
separation using an electric phoretic technique
3. hydrolysis- protein may be hydrolysis by heating with acid or alkaline or
proteolytic enzymes the products of hydrolysis are peptide and AA
4.8 Protein confirmation
This is the folding of polypeptide bond confirmation is the spatial
arrangement of atom that depend on the rotation of bonds we have several
level of protein confirmation (architecture) these are
a) Primary –it refers to the linear sequence of amino acids and the location
of disulphide bonds if any in a protein primary confirmation is the complete
description of covalent connection that are found in protein
b) Secondary –refers to the regular folding of the polypeptide backbone
without reference to the R-groups this folding may extent over hundreds of
amino acid residue or may change several time within short stretch of the
polypeptide
i. Example is helix which involve folding of a polypeptide in a helical or
spring like manner
ii. B-pleated sheets where we have side by side alignments of the
polypeptide chain
This sequence is held together by weak bond such as hydrogen
bonding

c) Tertiary structure refers to the overall folding of the polypeptide chain

that is both of the R-group and backbone taking part the polypeptide chain
tend to undergo extensive coiling /folding to produce a rigid structure the
backbone may have regular folding which is maintained by hydrogen
bonding other forces which are involve in the tertiary structure include
hydrophobic bond vander watt forces or ionic bonding
d) Quaternary structure –Degree of association of 2 or more polypeptide
chain to form a multi subunit protein the individual polypeptide unit in a
quaternary structure may be known as promoters’ monomers domains or
Page 53 of 86
subunit the quaternary structure is stabilized by hydrogen and hydrostatic
tore between surface residues of adjacent subunits
When the subunits are the same they are called hamodimer and if they are
different they are heterodimer

4.9 Protein denaturation

Protein denaturation refers to the partial or complete unfolding of specific
native confirmation of the polypeptide chain of a protein
Native protein –protein in their nature state –biological active
During denaturation protein lose physiological and physical properties
denaturation involve an alteration in weak bond that holds the structure
together but not the covalent forces of the primary structure
Denaturation is different from digestion because digestion involve the
hydrolysis of peptide bond i.e. it interferes with the primary structure

4.9.1 Agents of denaturation

i. Temperature-high temp increases thermal energy which in

consequence lead to an increase in vibration and rotational energy
that upsets the delicate balance of weak interaction of secondary
tertiary and quaternary structure this destabilizes the functionally
folded confirmation
ii. PH- changes in PH will alter the ionic states of the ion sable groups of
the proteins which include the amino group as well as the carboxyl
group in a protein this break the hydrogen bond and any other weak
force s creating regions of charge repulsion as well as disrupting the
ionic pair .this affect protein secondary, tertiary and quaternary
structures leading to denaturation e.g. when a protein acquire a large
negative positive and a large negative charges the ion sable groups
will repel each other placing the molecule under strain leading to
denuration.

Page 54 of 86
iii. Chaotropic agents -this include compounds such as urea and
quanidine hydrochloride. They are normally used as very high
concentration e.g.2M or [Link] chemicals disrupt the
secondary ,tertiary and quartenery structure by allowing water
molecule to penetrate into the interior where they solvate (form a shell
of H2O )the non-polar side chains disrupting the hydrophobic
interactions that normally stabilize the native confirmation. They
therefore weaken the hydrophobic interactions in the protein .This
chemicals also form a competing hydrogen bond with amino acid
residues of the peptide therefore destabilizing the internal hydrogen
bonding that stabilizes the reactive factors.
iv. Detergent (has both polar head and hydrophobic tail-amphipathic)
detergents have hydrophobic tail that penetrates into the hydrophobic
interior of the protein dissolving the hydrophobic interior by
denaturing. The association between the polypeptide chains also
disrupted by the detergents.
v. Thiol reagents e.g. B-mercaptoethanol. This reagent have a thiol
group (HOCH2CH2SH)
They have cleaves the disulphide bond .This bonds are reduced to the
sulphur hydrylgroups and the thiol reagent is disrupted
Other include heavy metal ions and organic solvent

Student Activity
1. Name and classify the 20 standard amino acids and give their 3-
letter symbols
2. Analyze your community’s diet and discuss the sources of protein
in it.
3. Discuss the quality of proteins in your diet

Page 55 of 86
 SELF-TEST QUESTIONS
1. Describe the functions of proteins
2. Explain obligatory nitrogen loss from the body and how it relates to
amino acid requirement.
3. Discuss protein classification and give examples
4. Draw and explain the formation of a peptide bond.
5. Discuss the methods used to determine protein quality

UNIT 5: ENZYMES
Unit objectives
By the end of this unit, the learner should be able to:
4. Explain the term iso-enzymes
5. Describe the structure of enzymes, classification and functions
6. Highlight factors affecting enzymatic activities
7. State the properties of enzymes and mode of action
8. Explain the role of enzymes in biochemical reactions
5.1 Definition
Enzymes;- are specialized proteins that are involved in catalysis i.e. they
spread up biological reaction. There are 2 types of enzymes depending on
where they are produced. They include; intracellular enzymes which are
used in the cell where they are produced. Extracellular enzymes are
produced by other cells and are secreted to other parts of the body where
they are utilized e.g. digestive enzyme.
Zymogen – enzymes which are produced in their inactive forms and they
have to be activated before they are able to function [Link].
Zymase – enzymes produced ready for action-Amylase.
Page 56 of 86
Substrate – substance upon which enzymes acts.
Active site of an enzyme - a small region on the enzyme where a
substrate binds for catalysis to take place.
5.2 Properties of enzymes
i. They are biological catalysts-this means they accelerate
biochemical reaction rate by reducing the energy of activation
needed to reach the transition stage between reactant and product.
The higher the activation energy the lower the reaction Enzymes
tends to lower the activation energy of a reaction .the reaction is
exothermic.
ii. Enzymes are true catalysts because they can enhance the rate of
specific reaction but do not get used up or shift the equilibrium of
reactions. They are not consumed regenerated during the reaction
and they are effective in the minute concentration is compared to
substrate concentration.
iii. They have high catalytic efficiency .A typical magazine will convert
around a thousand molecule of a substrate to a product in a second.
iv. They have substrate specificity; they are highly specific for the
reactant or substrates. For example some enzymes will only
catalyses one type of reaction for one type of compound. Some
enzymes will only recognize substrates structurally; similarly and
hence have a broad specificity.
v. They are temperature and PH dependant .They usually work on a
narrow PH range in most cases near neutrality although they are
some exception e.g. pepsin work on the range of 2-5.

5.3 Enzyme nomenclature and classification

Most enzymes are named by adding the suffix as to the name of the
substrate the can on or the descriptive term for the reaction they
catalyze we have exception of tryph.
Example: lactase –lacrose
Sucrose –sucrose
Page 57 of 86
We can also name enzyme depending on its action (function) e.g.
deoxyribonucles catalyst the conversion of DNA to deoxynucleotide
monophosphate (dnmp)
Classification can also be through enzyme commission system of
nomenclature. The first digit indicates the class to which the enzyme
belongs .The second and third digits will indicate the type of reaction
within that class in terms of the chemical groups involved. The fourth
digit is the individual number of the enzyme we only consider the class
according to the class there are six groups.
i. Oxidoreductases- this means they catalyze oxidation reduction
reactions i.e. redox reaction. Where there is transfer of electrons.
Hence they catalyze transfer of electrons from one substrate to
another.
Most of the oxidoroductase also referred to as dehydrogenises
but some are also known as oxidase, peroxidase, and reductase
etc. e.g. lactase dehydrogenase and alcohol dehydrogenase.
ii. Transferases – they catalyze group transfer reactions .i.e.
transfer of functional or molecules from one compound to
another many of this enzymes require the presence of co-
enzymes. In this reactions a portion of substrate molecule will
usually bond covalently to the enzyme or its [Link]
groups transfer in this reactions include phosphoryl, acyl, methyl,
amino, glyceryl, gre etc The general enzymes here are known as
kinases involve in the transfer of phosphate gre from ADP and
ATP Phosphorylases, methyl transferases- enzyme which transfer
methyl group: acyl transferases which will transfer aryl group.
iii. Hydrolases –they catalyze the hydrolysis of substrate by adding
constituent of water a cross the bond they Cleve break. These
enzyme cleve ester, amide and peptide bond they are a special
class of transferases with water serving as the acceptor of group
transfer

Page 58 of 86
 iv. Lyases – they catalyze non-hydrolytic and non-oxidative
elimination reactions or lysis (breakdown) of a substrate to
generate a double bond they may also catalyze reaction
involving addition a cross the double bond alyast enzyme that
catalyze the addition reaction in cells is known as syntheses
examples are decarboxylases which remove a carboxyl group to
form on a reaction (creating double bond) desmolases
v. Isomerases – they catalyze reaction that involve intermolecular
rearrangement i.e. transfer of groups within molecules to
generate isomeric form since this reaction have only one
substrate and one product they are among the simplest
enzymatic reaction examples are racemase catalyzing the
rearrange of an alpha –carbon atom .epimerases catalyse the
interconversion of epimeres
vi. Ligase -(joining)-they catalyse ligation or joining of two
substrate to form a covalent bond ligation require the input of
energy /ATP and ligast are usually referred to as synthetases
example is pyruvate carboxylase which catalyse the formation of
carbon ,carbon bond from pyruvate and co2 to form
oxalocecetate
5.4 Enzyme active site concept
Active site is a small region in the enzyme where a substrate binds for
catalysis to occur
5.4.1 Characteristics of the active site
1. The active site is a relatively small part volume of enzyme hence most
of the amino acids of the enzyme are not in contact with the substrate
2. The active site is usually complementary to the shape of the substrate
3. An active site is usually a cleft crevices or depressions on the surfaces
of the enzyme this clefts are usually hydrophobic i.e. water is usually
excloded from the clefts unless it is a reactant
4. Binding of the substrate in the enzyme active site usually includes a
conformational change this is particularly common where there are two
Page 59 of 86
 substrate and in this case binding of the first substrate sets up a
conformational change that results in the formation of binding site for
the 2nd substrate
5. The active sites contain catalytic group are reactive site chain of amino
acids or co-factors which carry out the bond breaking or forming
reaction
6. The binding of substrate in the enzyme active involve non-covalent
interactions such as van-derwaal hydrogen bonding the rest of the
enzyme structure provides a super structure to position the substrate
and catalytic groups flexibility for conformational changes means for
regulatory control and sites for recognition by other bio-molecules
5.4.2 Models of enzymes binding to the substrates
They are mechanisms proposed to show how enzymes bind to the substrate
during the catalytism which include;
i. Lock and key theory-put forward by emil fischer in [Link] this case
fischer visualized /hypothesized that the interaction of the substrate
and enzyme is analogous to a key and lock that means that the
enzyme and substrate must have a complementary or marking shape
for them to bind and therefore any variation in either structure will
disqualify the substrate from binding to the active site. This implies
that an active site is a rigid structure
ii. Induced fit theory put forward by Daniel koshland in 1958 initially the
enzyme does not have a specific /matching shape but when in contact
with a particular substrate there is a conformational change in the
enzyme that creates an active site that is now complimentary to the
substrate therefore binding takes place substrate analogue may cause
some but not all of the correct conformational changes
5.5 Enzyme kinetics
Kinetic refers to the study of reaction rates and factors that influence those
rates
5.5.1 Factors affecting rate of enzyme catalyzed reaction

Page 60 of 86
1. Temperature-its rise increases the number of molecules that can react
by both activating their kinetic energy and by increasing their
frequency of coalition .Reaction rate initially increases as temperature
rises owing to increase kinetic energy of the reacting
molecules .However excess kinetic energy of the enzyme will break the
hydrogen bonds well as the hydrophobic bond that maintain the
secondary ,tertiary and quaternary structure reacting to enzyme
denaturation with consequent loss of the catalytic activity.
Low temperature will lead to the inactivation of the enzyme leading to
decreased level of catalysis. Enzymes must therefore the optimal
temperature.

2. PH –has a marked effect on the enzyme activity because many have

ion sable groups which include COO-,NH+3 hence changes in PH will
modify the degree of the ionization of some or all of these groups and
this will affect the ionization of the enzyme molecule as a whole. This
may affect the enzyme in three ways:
a) Extreme PH may change the degree of ionization of many groups
in the enzyme so that there is a conformational change in the
enzyme that disturbs the three dimensional structure of the
enzyme activities because of the destruction of the secondary,
tertiary and quaternary structure.
b) Small changes in the PH will affect smaller numbers of ionsable
groups but if this happens to occur in the active site they may
cause a marked change in enzyme activity.
c) Changes in PH may cause change in the ionization of the
substrate and this could modify the binding of the substrate to
the enzyme upload of activity verse PH will give a better shape
curve with a well define PH optimum usually between 5-9 for
most enzymes.
3. Substrate concentration

Page 61 of 86
 At a fixed enzyme concentration the initial rate of reaction will increase
with substrate concentration until all molecules are saturated with the
substrate. This is known as saturation kinetics.
The reaction will reach a maximum when all enzymes are used until
any former increase in the concentration of substrate will have no
effect on the rate of reaction.
Saturation kinetic reflect the fact that reaction only occurs after the
substrate are bound to the enzyme and once all enzymes molecules
are bound no further increase is possible. Uncatalysed reaction does
not show this kinetics.

4. The enzyme concentration

They rate of chemical reaction will be directly proportional to enzyme
concentration provided there is availability of the substrate .in this
case there are more enzyme molecules on to which the substrate can
bind,
5. Presence of inhibitors
An inhibitor is a substance which is able to reduce the activity of the
enzyme .Hence the presence of inhibitors there is a decrease in the
rate of activity.
Activation energy –energy required for a reaction to take place

5.6 Mode of enzyme action

During catalysis an enzyme will bind to the substrate to form an enzyme
substrate complex (ES) for any chemical reaction to occur there has to be
activation energy the lesser the activation energy the faster the reaction
take place
The ES complex therefore has lower activation energy as compared to the
free enzyme or free substrate
At transition state is 50% that the reaction will take place or not
5.6.1 Enzymes inhibitors

Page 62 of 86
They are a molecule that negatively alters the rate of enzyme catalytic
reaction. Inhibitors will bind the enzyme during catalysis preventing enzyme
to speed up the reaction
The inhibitors therefore lower the amount of reacting therefore the rate of
reaction decreases
There are two types of enzyme inhibitors
i. Irreversible inhibitors –they bind irreversibly and covalent to the
enzyme and therefore destroy the enzyme molecules usually
irreversibly inhibitor are non-biological molecules such as organ
phosphorus and mercuric compounds the specificity of these inhibitors
is increased if they have a structural resemblance to the substrate of
the enzyme
ii. Reversible inhibitors-combine non-covalently with the enzyme and can
be easily removed from the enzyme by physical means such as dialysis
they under go rapid equilibrium binding and the velocity (rate)of
enzyme catalysed reaction is reduced by the formation of either
enzyme inhibitors complex or enzyme substrate inhibitors complex
there are 3 reversible inhibitors
 Competitive –they compete with the substrate to bind in the enzyme
active site they are structural analogues of the substrate therefore can
easily bind to the active site they will always bind in the enzyme active
site to form an EI complex that is catalytically inactive. The effect of a
competitive depends on the inhibitor concentration substrate
concentration and the relative affinities on the substrate and inhibitors
for the enzyme in this case binding of the either inhibitors on the
substrate on the enzyme on the enzyme active site are mutually
exclusive to overcome the effect of this inhibitors you increase the
substrate concentration
 Uncompetitive inhibitors-they bind specifically to enzyme substrate
complex and not to the free enzyme this may be cause substrate
binding may cause a conformational change to occur in an enzyme and
possible reveal an inhibitor could only be able to bind to the enzyme
Page 63 of 86
 bound substrate in neither case does the inhibitor complete with
substrate for the same binding site they will form an ESI as the dead
end complex
 Non-competitive-this can combine with an enzyme molecule to
produce a dead end complex regardless of whether a substrate is
bound or not they occur where the inhibitors must bind at a different
site from that of the substrate therefore the substrate and inhibitor will
bind reversibly randomly and independently in different site resulting
to E.S.I that is catalytically active

Page 64 of 86
UNIT 6: NUCLEIC ACIDS
Unit objectives
By the end of the lesson, the learner should be able to:
1. Define terms used describe the occurrence of nucleic acids
2. State the functions of DAN and RNA
3. Differentiate between nucleosides and nucleotides
4. Explain the sequence of proteins synthesis in the nucleus
Nucleic acids are high molecular weight polymers which occur in every living
cell.
Their main function is storage and transmission of genetic info. Two classes
of nucleic acid are distinguished according to types of CHO they contain.
i. Deoxyribonucleic acid (DNA)
ii. Ribonucleic acid (RNA)
DNA is a major constituent of chromosome located in the nucleus of the cell
but small amount are associated with cell organelle such as chloroplast and
mitochondria.
Nucleic acid are polymer of nucleotides and hence they may be called
polynucleotide sequence.
6.1 Nucleotides
They are building blocks of nucleid acid. They are made up of three
components:
1. Nitrogenous base
There are two types of nitrogenous;
I. Bicyclic purine
II. Monocyclic pyrimidine
a) Purines
Purines occur in two ways;
 Adenine
 Guanine

Page 65 of 86
Adenine and guanine are natural and there are other metabolic intermediate
such as xathine and hypoxathiane that are formed by breakdown of adenine
and guamine.
b) Pyrimidine
Consist of a six member ring with two nitrogen atom, the main pyrimidine
basis are :
 Cytocine (RNA & DNA)
 Uracil (RNA)
 Thyamine (DNA)
Uracil is found in RNA and THIAMINE is almost exclusively in DNA.
c) Pentose sugar
Pentose sugar in DNA is 2 deoxyribose acid and in RNA is D- ribose
The sugar must have a better configuration. They help to form the backbone
of DNA molecule.
6.2 Phosphate group
These usually form a phosphodiester bond with OH group of carbon number
5 of pentose sugar.
When nitrogenous base is added to a pentose sugar you get nucleosides.
 Nucleosides
When nitrogenous base is linked to a pentose sugar through a
glycosidic bond with loss of water component the resulting compound
is called Nucleosides.
A base linked to a ribose sugar is called riboside e.g. Adenine will form
adenosine and when the sugar is dexyl-d-ribose we get deoxyribosides.
Nucleotides are phosphor related nucleosides; the phosphoric acid is bound
to CH2OH of the sugar molecule by an ester bond.
The compound thus formed is called monophosphate. Of the base
If the phosphate groups are two it will be adenosine diphoshate (ADP)
If the phosphate group are three it will be adenosine triphoshoshate (ATP)
To distinguish between numbering of nitrogenous base and sugar ring the
pentose sugar carbon atom are designated by prine e.g 1’-5’
Natural occurring nucleotide includes:
Page 66 of 86
 i. Adenosine nucleotide include:ATP ADP AMP and cyclic Amp
ii. Gaonosine nucleotide include GTP GDP GMP and cyclic Gmp
iii. Cystidine nucleotide include CTR CDP cmp and cyclic cmp
iv. Uridine nucleotide include UTP UDP Ump and cyclic ump
Ribose molecule bound to a base passes free hydroxyl group on 2’3’ and 5’
carbon atoms hence phosphate residue can be attached to any of these
Incase of deoxy-d-ribose derivates only 3’ and 5’ carbon position are
available for attachments of phosphoric and molecule
ATP<Adenosine Triphoshate>
In ATP two of three phosphate residue are high energy phosphate and on
hydrolysis each release energy which is used in endogenic process or bio
synthesis of fatty acids proteins peptides e.t.c
It is also an important source of energy in muscle contraction transmission of
nerve impulses transport of nutrient across cell membrane it is also a good
donor of phosphate group for a variety of reaction
6.3 Metabolic function of nucleotides
i. They have a role in energy metabolism e.g ATP which is generated in
cell and is used in many metabolic reaction as phoshorelating agent
e.g glycolysis
ii. They are building block of nucleic acid which are RNA and DNA
iii. They act as physiological mediators they act as key mediators in many
metabolic processes e.g cylic Amp which plays a second messenger
role in many hormone action
iv. They are components of major co-enzymes <organic molecules that
are required for optimum enzyme action > they are active form of
vitamin and will bind non-convalently to the enzyme during catalysis
the co-enzymes formed from nucleotide include NAD <nicotimamide
Adenine denudeotide> these is a co-enzyme derived from niacin FAD
(flavin adenine dinucleotide )derived from riboflavin (B2)
v. They act as activated intermediate they serve as carriers of activated
intermediate for variety of reactions e.g GDP will act as intermediate in
fructose and UDP in galactose
Page 67 of 86
6.4 Nucleic acids
6.4.1 DNA
A single strand of DNA is polymer of nucleotides bonded to one another by
3’-5’ phosphodiester bond
The backbone of polymer is called sugar phosphate backbone because it is
composed of alternating unit of 5 carbon sugar of 2’ deoxyribose and a
phosphate group in a phosphodiester linkage
The DNA consist of double stranded helix formed by 2 poly
deoxyribonucleotide strands
Each of the two strands are called about a central [Link] sugar phosphate
backbone wind around the outside of the [Link] phosphodiester bond in
the 2 interwoven strands run in opposite direction i.e. they are anti-
[Link] run 5’3’ while the others run 3’ to 5’.
The 3’-5’ is called non-coding <doesn’t give information >or nonsense
strands the admire strand of DNA is hydrogen bonded to cytosine. There are
called the base pair.
The two strands of DNA are complementary strands because the sequence of
bases on automatically determines in sequence or bases on the other when
there is an adenine on one strand there will always be a thymine in the same
location on the opposite strand.
The ratio of pyrine to pyrimidine base in DNA molecules is always one.
6.4.2 RNA
The sugar phosphate backbone of RNA consists of ribonucleotides also linked
by 3’ 5’ phosphodiester bond. These phosphodiester bond are identical to
those found in DNA however RNA molecules differ from DNA molecules in
those basic properties
RNA molecules are usually single bond stranded
The sugar phosphate backbone of RNA consist of ribonucleotides linked by 3’
5’ phosphodiester bonds
These sugar ribose is found in spare of 2 deoxyribose

Page 68 of 86
The nitrogenous base uracil replaces thymine although RNA molecules are
single stranded base pairing between uracil and adenine and between
Quanine and cytosine can skill occur
Classes of RNA molecules
Three classes of RNA molecules are produced by transcription messenger
RNA transfer RNA and ribosomal RNA
1. Messenger RNA <MRNA> carries the scientific information for a protein
from DNA to the ribosomes it is a complementary RNA copy of agene
on the DNA
2. Ribosomal RNA (Rrna) its astructural and functional component of the
ribosome which are plate forms on which protein synthesis occurs
3. Transfer RNA (t RNA) consist about 10-20 of total celluar RNA
molecules there are at least 20 different tRNA molecules in every cell
and this correspond to 20 amino acid require for protein synthesis Trna
contain a site for attachement for amino acid and site that interact
with MRN known as anticodon TRNA fail back to themselves to form a
colour leaf with lither 4 or 5 double stranded paired stem
6.4.3 DNA function
i. Control of a cell activities to produce characteristics of an individual
and species
ii. Replication in order for material to be passed on from cell to cell
generation and for growth via meosis and mitosis
iii. Undergo mutation permanent change passed onto offspring may
advance to species via evolution
Each chromosome contain many liters most act as a blueprint on set of
instruction for the cell
Chromosome are mainly chromatin threads each containing DNA and protein
Somatic cells contains 46 chromosomes genetic cells contain 23
chromosomes 44 of our chromosome are auto some while two are called
sebc chromosomes
6.5 Genetic code

Page 69 of 86
The genetic code is the set of rules by which information encoded within genetic
material (DNA or mRNA sequences) is translated into proteins by living cells.
Biological decoding is accomplished by the ribosome, which links amino acids in an
order specified by mRNA, using transfer RNA (tRNA) molecules to carry amino acids
and to read the mRNA three nucleotides at a time. The genetic code is highly similar
among all organisms and can be expressed in a simple table with 64 entries.
The code defines how sequences of these nucleotide triplets, called codons,
specify which amino acid will be added next during protein synthesis. With
some exceptions, a three-nucleotide codon in a nucleic acid sequence
specifies a single amino acid. Because the vast majority of genes are
encoded with exactly the same code, this particular code is often referred to
as the canonical or standard genetic code, or simply thegenetic code, though
in fact some variant codes have evolved. For example, protein synthesis in
human mitochondria relies on a genetic code that differs from the standard
genetic code.
Serious efforts to understand how proteins are encoded began after the
structure of DNA was discovered in 1953. George Gamow postulated that
sets of three bases must be employed to encode the 20 standard amino
acids used by living cells to build proteins. With four different nucleotides, a
code of 2 nucleotides would allow for only a maximum of 42 = 16 amino
acids. A code of 3 nucleotides could code for a maximum of 43 = 64 amino
acids.
The Crick, Brenner et al. experiment first demonstrated that codons consist
of three DNA bases. They used a cell-free system to translate a poly-uracil
RNA sequence (i.e., UUUUU...) and discovered that the polypeptide that they
had synthesized consisted of only the amino acid phenylalanine. They
thereby deduced that the codon UUU specified the amino acid phenylalanine.
This was followed by experiments in laboratory that demonstrated that the
poly-adenine RNA sequence (AAAAA...) coded for the polypeptide poly-lysine
and that the poly-cytosine RNA sequence (CCCCC...) coded for the
polypeptide poly-proline. Therefore the codon AAA specified the amino acid
lysine, and the codon CCC specified the amino acid proline. Using different

Page 70 of 86
copolymers most of the remaining codons were then determined.
Subsequent work by Har Gobind Khorana identified the rest of the genetic
code. Shortly thereafter, Robert W. Holley determined the structure of
transfer RNA (tRNA), the adapter molecule that facilitates the process of
translating RNA into protein.
6.5.1 Characteristics of Genetic Code
 The genetic code is a triplet code: Three adjacent bases, termed as
codon, specify one amino acid
 Non-overlapping: Adjacent codonS do not overlap.
 No punctuation: The genetic code is comma less.
 The genetic code is universal i.e., a given codon specifies the same
amino acid in all protein synthesising organisms.
 The genetic code is degenerate: it lacks specificity and one amino acid
often has more than one code triplet.
 Each codon codes for only one amino acid, none for more than one.
 Three of the 64 codons, names UAA, UAG and UGA do not specify any
amino acid but signal the end of the message. They are called
nonsense or terminator codons.
 The codons AUG and GUG are called the initiation or start codons as they begin the synthesis of
polypeptide.

Second nucleotide

U C A G

UUU Phenylalanine UCU Serine UAU Tyrosine UGU Cysteine

U
(Phe) (Ser) (Tyr) (Cys)

UUC Phe UCC Ser UAC Tyr UGC Cys C

U UUA Leucine (Leu) UCA Ser UAA STOP UGA STOP A

UGG
UUG Leu UCG Ser UAG STOP Tryptophan G
(Trp)

C CUU Leucine (Leu) CCU Proline CAU Histidine CGU Arginine U

Page 71 of 86
 (Pro) (His) (Arg)

CUC Leu CCC Pro CAC His CGC Arg C

CAA Glutamine
CUA Leu CCA Pro CGA Arg A
(Gln)

CUG Leu CCG Pro CAG Gln CGG Arg G

ACU AAU
AGU Serine
AUU Isoleucine (Ile) Threonine Asparagine U
(Ser)
(Thr) (Asn)

AUC Ile ACC Thr AAC Asn AGC Ser C

A
AGA Arginine
AUA Ile ACA Thr AAA Lysine (Lys) A
(Arg)

AUG Methionine
ACG Thr AAG Lys AGG Arg G
(Met) or START

GCU Alanine GAU Aspartic GGU Glycine

GUU Valine Val U
(Ala) acid (Asp) (Gly)

GUC (Val) GCC Ala GAC Asp GGC Gly C

G
GAA Glutamic
GUA Val GCA Ala GGA Gly A
acid (Glu)

GUG Val GCG Ala GAG Glu GGG Gly G

6.5.2 Transcription
Before the synthesis of a protein begins, the corresponding RNA molecule is
produced by RNA transcription. One strand of the DNA double helix is used
as a template by the RNA polymerase to synthesize a messenger RNA
(mRNA). This mRNA migrates from the nucleus to the cytoplasm. During this
step, mRNA goes through different types of maturation including one called
splicing when the non-coding sequences are eliminated. The coding mRNA
sequence can be described as a unit of three nucleotides called a codon.

Page 72 of 86
The process of translation can be broken down into three stages. The first
stage is initiation. In this step, a special "initiator" tRNA carrying the amino
acid methionine binds to a special site on the small subunit of the ribosome
(the ribosome is composed of two subunits, the small subunit and the large
subunit). The mRNA is also loaded on, and positioned so that the initiation
codon (usually AUG) is base paired with the anticodon of the initiator tRNA.
The large subunit then binds to the small subunit. The resulting complex of
ribosome, mRNA, and methionine-bearing initiator tRNA is called an initiation
complex. Formation of this complex also requires a number of helper
proteins called initiation factors.
The second stage is called chain elongation. During this stage, additional
amino acids are progressively added. The methionine-bearing initiator tRNA
sits on a site of the ribosome called the P (peptidyl) site. A new tRNA, bearing
the next amino acid is base paired via its anticodon to the next codon of the
mRNA, using a site called the A (acceptor) site. This new amino acid is then
attached to the amino acid carried by the P site tRNA, forming a peptide
bond. This enzymatic step is carried out by the ribosome, at a site called the
peptidyl-transferase center.
The tRNA that has so far been attached to the amino acid in the P site is then
released through the E (exit) site, and the new tRNA, now carrying both its
own amino acid and the methionine moves into the P site. The mRNA also
slides three bases to bring the next codon into position at the A site. A
t78hird tRNA, again carrying a specific amino acid and recognizing the third
codon of the mRNA, moves into the A site, and the cycle is repeated. As
these steps are continued, the mRNA slides along the ribosome, three bases
at a time, and the peptide (amino acid) chain continues to grow. As with
initiation, elongation requires helper proteins, called elongation factors.
Energy is also required for peptide bond formation.
The final stage of translation is termination. The signal to stop adding amino
acids to the polypeptide is a stop codon (UAA, UAG, or UGA), for which there
is no partner tRNA. Rather, special proteins called release factors bind to the
A site of the ribosome and trigger an enzymatic reaction by the ribosome.
Page 73 of 86
This reaction causes the ribosome to release the polypeptide and mRNA,
ending the elongation process.
At a given time, more than one ribosome may be translating a single mRNA
molecule. The resulting clusters of ribosomes, which resemble beads on a
string, are called polysomes

UNIT 7: BIOENERGETICS
Unit objectives
By the end of the lesson the learner should be able to:
1. Define terms as used in bioenergetics
2. State the functions of energetic
3. Highlight sources of energy and inter=convertibility
4. State the laws of thermodynamics
7.1

Page 74 of 86
UNIT 8: HORMONES
Unit objectives
By the end of the lesson the learner should be able to:
1. State the organization of mammalian hormone system
2. Explain the functions of various hormones
3. Describe the secretion, mode of action and regulation of hormones
4. Explain the role of nucleic adenophosphate on the secretion action
5. List the clinical disorders of hormone deficiencies and excesses
8.1 Hormones are regulatory substances produced in an organism and
transported in tissue fluids such as blood to stimulate specific cells or tissues
into action. Is any member of a class of signaling molecules produced by
glands in multicellular organisms that are transported by the circulatory
system to target distant organs to regulate physiology and behavior
8.2 Functions of various hormones
1. Thyroid hormones
a) Growth and development they exact an important effect on protein
synthesis
b) Have cardiovascular effect under the influence of thyroid hormones
heart becomes rapid resulting in enhanced cardiac output
c) Stimulates oxygen consumption
d) They regulate carbohydrate lipids and protein metabolism
2. Adrenal cortisol hormone
a) Glucocotticiods that have effects on metabolism of proteins
carbohydrates
3. Ieutinizing hormone
It causes the ovulation and development of corpus leuteum in men it is the
source of production of testicular androgens
4. Follicle stimulating hormone
It influences the ovarian follicle to start developing stimulate the secretion of
oestrogen and progesterone
5. Growth hormone
Page 75 of 86
Promotes the linear growth of the long bones it aids in nitrogen calcium
phosphrous and carbohydrates metabolism
6. Insulin
i. stimulates glycolysis and short down citric acid cycles by inhibiting
several enzymes
ii. stimulates the uptake of glucose within the cells
iii. promotes storage of glucose and fatty acids
iv. decreases the blood glucose levels
v. increases glucose and amino acid transport
vi. promotes transport of K+ intracellulaly

7. Oestrogen
i. Are primarily responsible for the maintenance of the female
reproduction hormones the principle target organs are uterus ovary
vagina and mammary glands that show growth and maturation under
the impact of oestrogen the hormone prepares the ovary for ovulation
it also has a profound influence on certain metabolic functions e.g.
increased protein synthesis lipid metabolism and elevation of serum
calcium and phosphorus and fats
ii. Mineral corticoids which affects the electrolyte and water balance in
the body
iii. Oestrogens and androgens produced by ovaries and testis and affect
female and male sexual characteristics
iv. Prolactine hormone it is responsible for the secretion of milk and is
essential for the development and differentiation of mammary glands
in the preparation for milk production after child birth

8. Oxytocin
Mainly functions in stimulating smooth muscle contraction parturition and
circ neutral reflexes arising from the cervix and vagina stimulates the
secretion of oxytocin which in turn causes contraction in the uterine smooth
muscle circling of the breast also stimulates the contraction of oxytocin
Page 76 of 86
resulting the myoepithelial cells around the alveoli channels in the mammary
glands the milk start following through the nipple where it is available in the
infant thus oxytocin induces milk ejection it has a direct effect on vascular
smooth muscles it is a weak constrictor of renal and skeletal muscles at
arteries and it is a powerful of ambilical arteries and veins it has an effect on
contraction of urinary and gallbladder muscles
9. Vasopressin
It’s also called the ADH its major effect include water reabsorption from
distal and collecting tubules of kidneys and it also stimulates glycogenolysis
in the liver oxytosin another hormone made in the hypothalamus cause
uterine contraction during childbirth and milk let down when the body is
nursing the more the uterus contract during labour the more nerve impulses
reach the hypothalamus causing oxytocin to the release the more a baby
circles the more oxytocin from the exterior pituitary is controlled by positive
feedback the stimulus continue to bring about an effect that ever increases
in intensity
10. Progesterone
This is a hormone of corpus leuteum and it shows its appearance after
ovulation incase of pregnancy the hormone is essential for its maintenance
and growth of breast
It suppresses ovulation and luteinizing hormone
11. Anterior pituitary
This is a potol system consisting of two capillary system connected by a vein
lies between the hypothalamus and the posterior pituitary the hypothalamus
controller the anterior pituitary by producing hypothalamic releasing
hormones and hypotherlamic inhibiting hormone e.g. there is thyroid
releasing hormone and thyroid inhibiting hormone thyroid releasing hormone
8.3 Clinical disorders of hormone deficiencies and excesses
1. Hypogonadism
Is when the sex glands produce little or no hormones in men the thest glands
(gonads are testes) in women they are the ovaries can be primary cause or
central
Page 77 of 86
Some primary hypogonadism include
i. Genetic and dev disorders
ii. Infection
iii. Liver and kidney disease
iv. Radiation
v. Surgery
Causes of hypogonadism
i. Bleeding
ii. Certain medication including steroids
iii. Genetic problems
iv. Infections
v. Nistrition deficiencies
vi. Radiation
vii. Excess iron
viii. Rapid significant weight loss
ix. Surgery
x. Trauma
xi. Tumors
Symptoms
Girls who have hypogonadism during childhood will not begin menstruating
the condition can affect girls breast development and height if it occurs after
puberty it leads to loss of body hair hot flashes low libido menstruation chops
In boys hypogonalism in childhood affect muscle and bearal development
and leads to growth problems in men the symptoms are breast enlargement
decreased beard and body hair muscle loss sexual problems
The removal as destruction of a portion of thyroid gland by means of a radio
active iodine i.e. sometimes effective in cutting this addition

2. Malfunction of adrenal contex hormone

When the level of adrenal contex is low due to hypo secretion a person
develops Addison disease without the cartisal glucose cannot be replenished
when a stressful situation arises even a mild infection can lead to death the
Page 78 of 86
lack of aldosterone result in a loss of sodium and water the development of
low blood pressure and possibly severe dehydration
If left untreated addison disease can be fatal when the level of adrenal
contex hormone is high due to hyper secretion a person develops a …….
Syndrome the excess cartisol results in a tendency towards diabetes mellitus
as muscle protein is metabolized and subcutaneous fats is deposited in the
mid section the frunk is obese while the arm and legs remain a normal size
an excess of aldosterone and reabsorption of ceater and sodium by the
kidney leads to basic blood PH and hypertension the face is moon shaped
due to oedema
Musculanization may occur in women because of excess adrenal male sex
hormones

3. Malfunctioning of thyroid hormones

To produce thyroxin the thyroid glands actively acquires iodine. If iodine is
lacking in the diet the thyroid is unable to produce the thyroid hormones
In response to constant stimulation by the anterior pituitary the thyroid
enlarge resulting in a single goiter if the thyroid finds to develop properly a
condition known as cretinism results individuals with this condition are short
and stocky and have had extreme hypothyroidism since infancy or child hood
thyroid hormone therapy can initiate growth but unless treatment is began
within the 1st two months of life mental retardation results
The occurrence of hypothyroidism in adults produces the condition known as
myxedema which is characterized by
i. weight gain
ii. loss of hair
iii. slower pulse rate
iv. lower body temperature
v. thickness and puffiness of the skin
The administration of adequate closes of thyroid hormone restore the normal
function of capillaries in the case of hyperthyroidism(grave disease ) the
thyroid gland is overactive and a goiter forms this type of goiter is known as
Page 79 of 86
exothermic goiter the eye protrude because of oedema in the eye socket
tissues and swelling of the muscle that moves the eye the patient usually
becomes hyperactive nerves irritable and suffer from insomnia the hormone
has a stimulating effect on the smooth muscles of the interline and uterus

Page 80 of 86
UNIT 9: MUSCLES
Unit objectives
By the end of this lesson, the learner should be able to:
1. List the types and functions and muscles
2. Describe the structure of muscles, contraction, biochemical and physical
changes
Muscles is a contractile tissue of animals and is derived from the muscle
dermal layer of embrogonic germ cell
Muscle cells contain contractile filaments that moves past each other and
change the size of the cell
9.1 Functions of muscles
i. Involved in motion
ii. Help in maintaining the posture
iii. They are involved in heat production
9.2 Characteristics of muscles
i. Excitability-they respond to stimuli
ii. Contractility-they are able to shorten in length
iii. Extensibility-stretches when pulled
iv. Elasticity-they tend to restore the original shape and length after
contraction and extension
v. Conductivity-electrical charges are spread through the entire muscle
fibre and initiates the process that leads to muscle contraction
9.3 Types of muscles
Human have three types of muscles
i. Skeletal muscles
ii. Cardiac muscles
iii. Smooth muscles
I) Smooth muscles
They are spindle shaped each with a single nucleolus (they are uninucleated)
The cells are usually red in parallel lines forming shapes
Page 81 of 86
The striation does not occur in these muscles
Smooth muscle is located in the walls of hollow internal organs and it causes
these walls to contract
The contraction of smooth muscle is involuntary i.e. it occurs without
conscious control although smooth muscle is lower to contract than skeletal
muscle it can sustain and cannot fatigue easily e.g. peristalsis
II) Cardiac muscles
Forms the heart walls
Its fibers are uninucleated they are striated tubular and branch which allows
the fibers to interlock at intercalated discs
Intercalated discs permits contraction to spread quickly through out the
heart
Cardiac fibers relax completely between contraction which prevents fatigue
contraction of the cardiac muscles is rhythmically it occurs without outside
nervous stimulation and without unconscious control
III) Skeletal muscles
Its fibers are tubular multinucleated and striated they make up the skeletal
muscles attached to the skeletal
They run length of the muscle and they can be quiet long
Skeletal muscle is voluntary because its contraction can be consciously
stimulated and controlled by the nerves system
They have numerous functions
9.4 Functions of the skeletal muscles
1. They support the body
Skeletal muscle contraction opposes the force of gravity and allows us to
remain upright
2. Makes the bones move muscle contraction accounts not only for the
movement of arms and legs but also for the movement of eyes and facial
expression
3. Skeletal muscles help maintain a constant body temperature skeletal
muscle contraction causes the ATP to breakdown releasing heat that is
distributed about the body
Page 82 of 86
4. Skeletal muscle contraction assist movement in cardiovascular and in fatty
vessels the pressure of the skeletal muscle contraction keeps blood moving
in the cardiovascular veins and lymph in the lymphatic vessels
5. Skeletal muscles protects internal organs and stabilize joints the muscle
pad the bones that protect organs and they have tendons that help hold
bones bound together to joints

9.5 Structure of the muscle

Each muscle is an organ composed of several tissues
Its essential constituents is a number of fibers consisting of stripped
muscular tissue they are supported and protected by connective tissues
intertwined with blood and lymph vessels which conveys nourishments
The cross-sectional area of a muscle determines the amount of force. It can
generate by defining the number of sarcomeres which can operate in parallel
A muscle is mainly composed with muscle cells within the cells are myofibrils
which contain sarcomeres which are composed of
i. Actin
ii. Myosin
Individual muscle fiber are surrounded by endomysium
Muscle fiber are joined together by perimysium into bundles called fascicles
the bundles are put together to form muscle endorsed in a sheath known as
epimysium
Endomysium
Within the muscle
It’s the inner most tissue layer that surrounds the muscle
Perimysium
Means around muscles
It surrounds bundle of the muscle fiber called fascicles
Epimysium
It’s a layer of dense irregular connective tissue that surrounds the whole
skeletal muscle
Page 83 of 86
Physical changes during muscle contraction
1. Shortening of the muscle fiber
During muscle contraction the sacormere shortens by about 60-70 %
2. Viscosity
During muscle contraction and density of the sacomere increase
3. Iconicity
Passion contraction of a relaxed muscle is called tonace during muscle
contraction the tonicity increase during as more and more motor units comes
into the face of contraction

4. Heat production
The energy released by ATP during muscle contraction is partially converted
into heat
5. Electric changes
The sacormere is with a rest 90 MV during contraction an action potential of
45MV to 50MV is developed
9.6 Biochemical changes during muscle contraction
During muscle contraction a number of biochemical changes occurs in
resting muscle fiber surcolemma is electro positive outside and
electronegative inside this potential difference across a membrane is called a
resting potential
A membrane with such a resting potential is said to be polarized Na+ ions
predominate the outside of the sarcolemna while the potassium ion
predominate the inside
Due to the difference in the concentration on the two sides of the sacormere
potassium ions links leave and the sodium ions enters the muscle fiber
sacomere is more permeable to potassium ions than Na+ hence the K+
leaves the muscle fiber faster than the sodium ion enter and this builds a
positive charge outside when the motor nerve impulse reaches the neurone

Page 84 of 86
muscular junction the vesicles present in the motor end plate secret a neuro
transmitter chemical known as acetycholine (Ach)
Ach binds to the receptor on the sarcolemma making it more permeable to
Na+ than K+ so that Na+ rapidly diffuse along the concentration gradients
and electrical gradient now the sacomere becomes electro positive inside
and electro negative outside this new difference is called the action potential
such sacomere is called depolarized
9.7 Mechanism of muscle contraction
The sequence of events leading to contraction is initiated somewhere in the
central nervous system either as voluntary activity from the brain or as
reflex activity from the spinal cord
A motor neuron in the ventral horn of the spinal cord is activated and an
action potential passes outward in a ventral root of the spinal cord
The axon branches to supply a number of muscle fibers called motor unit
and the action potential is conveyed to a motor end plate on each muscle
fiber
At the motor and plate the action potential causes the release of packets or
quanta of acetylcholine into the synaptic defts on the surface of the muscle
fiber
Acetycholine causes the electrical resting potential under the motor end
plate to change and this then initiates an action potential which passes in
both directions along the surface of muscle fiber
At the opening of each transverse tubule into the muscle fiber surface the
action potential spreads inside the muscle fiber
At each point where a transverse tubule touches part of the sacroplasmic
reticulum it causes the sarcoplasmic reticulum to release calcium ions
The calcium ions result in movement of troponin and tropomyosin on their
thin filaments and this enables the myosin molecule needs to grab and swirel
their way along the thin filament this is the dividing force of muscle contract.

Page 85 of 86
REFERENCES
1. Albert I. Lehninger; (2007) Principles Of Biochemistry; 1 st edition; worth
publishers; new York
2. Chatterjea M. N and Rana Shinde; (2002) Medical Biochemistry. 8 th
edition, Jaypee brothers publishers; New delhi
3. Conn Eric E, and Stumpf P. K (1994). Outline Of Biochemistry; 4 th edition.
Wiley Eastern limited; London

DIP_BASIC BIOCHEMISTRY_EMBU ZERO DRAFT

Page 86 of 86