UNIT 1: MOLECULES, DIET, TRANSPORT AND HEALTH

TOPIC 1 – MOLECULES, TRANSPORT AND HEALTH

BIOLGICAL MOLECULES

- These are molecules that constitute life.

- They include:
o Water
o Carbohydrates
o Lipids
o Proteins
o Nucleic acids

WATER

- A water molecule consists of 2 hydrogen atoms and 1 oxygen

- Each hydrogen atom shares electrons with an oxygen atom but the electrons are not equally
shared. This causes water to have an uneven distribution of charge.
- Oxygen has a higher pull on electrons and this draws electrons closer to the oxygen atom and
causes a slight negative (-) on the oxygen atom and causes a slight positive charge on the
hydrogen atom (+). This means that there are small amounts of positive and negative charge on
the water molecule as shown below.

The water molecules are attracted to one another by hydrogen bonds (weak a weak electrostatic
force) formed between the slightly negatively charged oxygen atom and the slightly positively charged
hydrogen atom as shown below.

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PROPERTIES OF WATER
1. Dipole nature (Dipolar)
- The slight negative charge on oxygen atom and the slight positive charge on hydrogen makes
a water molecule have a dipole nature.
- The condition where in a molecule one side is slightly positive and the other side is slightly
negative is called dipole and the molecule is called dipolar.
2. Water has a high melting and boiling point compared to other molecular substances of similar
mass.
- This is because it requires more energy to break the hydrogen bonds in addition to the covalent
bonds. Although the hydrogen bonds are weak, they are very many.
3. It has a high specific heat capacity
- It requires high amount of energy to raise or lower the temperature of one gram of water by 1 0c
4. Cohesive properties
- The slight negative charge on oxygen of one water molecule attracts the slight positive charge of
hydrogen of another water molecule forming a hydrogen bond. This makes water molecules to
stick together.
5. It has a high surface tension
- At the air – water interface, the cohesion forces between water molecules causes water
molecules on the surface to form hydrogen bonds with other water molecules around and below
but not with the air molecules above.
- This makes the water to behave as if the whole surface is covered with a thin elastic sheet.
- This enables aquatic plants to float on water and small animals to walk on water and offer
support to large animals to swim.
6. Water has high latent heat of vaporisation.
- High amount of heat energy is needed to change 1g of water to gas .This is due to the presence
of hydrogen bonds in addition to the covalent bonds.
7. Unusual freezing density / Unusual expansion of water
- Water has a maximum density at 40C and not 00C.
- At 40C water is still liquid but at 00C it becomes solid (ice).
- The solid ice is less dense than the liquid water therefore the ice floats above the liquid water.
- When water freezes, hydrogen bonds strengthen and this causes the water structure to open up,
increasing the volume and decreasing the density i.e. water expands as it freezes.
- The importance of this is that ice acts as a heat insulator so that the lower atmospheric
temperature during winter does not affect the water below the ice, hence the water below this ice
remains relatively warm for the survival of aquatic animals.

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BIOLOGICAL ROLES OF WATER
1. Water is a solvent
Due to the dipole nature water dissolves many substances
Examples;
a) Ionic substances such as sodium chloride which dissolves to form a solution. The positive
ion (Na+) is attracted to the - charge of oxygen and the negative ion (Cl -) is attracted to
the + charge on hydrogen. This makes the ionic substance to separate and go into
solution.
b) Covalent compounds such as ethanol and sugar that have hydroxyl group to which water
molecules are attracted to.
c) Non polar substances with large molecules form colloids in water e.g proteins. The
molecules spread out in water but do not separate
d) Insoluble particles with small molecules form emulsions in water. They become suspended
as tiny droplets.

2. Transport medium
The cohesive property of water due to presence of hydrogen bonds enables transport of
materials within organisms in solution form, emulsions or colloids e.g. transport of ions in
solution form in the xylem and transport of soluble products of digestion.
NB: Not all lipids are transported in form of emulsions, most lipids are transported by
lipoproteins in blood.

3. As a coolant
Due to hydrogen bonding, high energy is required to break these hydrogen bonds in
addition to covalent bonds to change water into gaseous state.
Therefore, heat energy from the body is used to evaporate the water in the sweat hence
cooling the body.

4. Maintaining body temperature relatively constant

Due to the high specific heat capacity of water because of hydrogen bonding, a lot of
energy must be lost for the temperature of 1g of water to fall by 1 oc. Likewise a lot of
energy must be gained for the temperature of 1g of water to rise by 1 oc.
This is important in living organisms because sudden changes in body temperature are
avoided.
Most of the excess heat produced in the body is taken up by the water.
It also prevents large fluctuations of temperature of a water body enabling aquatic
organisms to survive.

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 5. As a reagent.
Water is important in metabolic reactions such as hydrolysis. During hydrolysis, water
molecules break large molecules into smaller subunits e.g. hydrolysis of maltose into
glucose

6. Water acts as abuffer.

Water molecules can donate H+ ions and OH- ions. Therefore water molecules can act as
an acid or a base. This helps to controlpH during biochemical reactions whereby the
excess H+ ions or OH- ions can be taken up by water.

7. Water is used as a raw material during photosynthesis where it’s a source of H +

CARBOHYDRATES
Contain 3 elements: Carbon (C), Hydrogen (H) and Oxygen (O)
Functions of carbohydrates
1. Source of energy e.g glucose
2. Store of energy e.g. starch and glycogen
3. Forms body structure e.g cellulose
4. Source of metabolic water when broken down

 Carbohydrates are found in one of the three forms:

1. Monosaccharides
2. Disaccharides
3. Polysaccharides

MONOSACCHARIDES
- These are the simplest sugars.
General formula for monosaccharides is CnH2nOn, where n is 3 to 9.
Common monosaccharides with 5 or more carbon atoms occur in ring forms

PENTOSES

- They are monosaccharides with 5 carbons.

- There are 2 main types of pentoses;
a) Ribose (C5H10O5)
b) Deoxyribose (C5H10O4)
- The difference between ribose and deoxyribose is that on carbon atom 2, ribose has OH group
and deoxyribose has just H group (deoxyribose lacks a oxygen at carbon number 2)

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- The importance of pentoses include:
a) Synthesis of nucleic acids i.e. DNA and RNA.
DNA consists of deoxyribose while RNA consists of ribose
b) Synthesis of a nucleotide co-enzymes (hydrogen acceptors) such as NAD, NADP and FAD
c) Synthesis of molecules such as ATP (Adenosine triphosphate), ADP (Adenosine
diphosphate), and AMP (Adenosine monophosphate).
HEXOSES

- These are monosaccharides with 6 carbon atoms.

- They consist of both linear and ring forms.
- Their chemical formula is C6H12O6.
- The common hexoses are glucose, fructose and galactose
Glucose
- There are 2 isomers of glucose
a)  - glucose
b)  - glucose

 - glucose  - glucose

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- In  - glucose, OH- on carbon number one (C1) is below the ring while, in  - glucose the, OH- is
on carbon number one (C1) is above the ring.

Galactose
- There are 2 isomers of galactose
c)  - galactose
d)  - galacose

- In  - galactose, OH- on carbon number one (C1) is below the ring while, in  - galactose the, OH-
is on carbon number one (C1) is above the ring.
 Galactose is identical to glucose except for the OH- group on carbon number 4, where, in
glucose the OH- group is always below the ring while in galacttose the OH- group is always
above the ring.
Fructose
- There are 2 isomers of glucose
e)  - sucrose
f)  - sucrose

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  - Fructose  - Fructose

- In  - glucose, OH- on carbon number one (C1) is below the ring while, in  - glucose the, OH- is
on carbon number one (C1) is above the ring.

DISACCHARIDES
- The formula for disaccharide is CnH2n-2On-1, where n is 12
- They are sugars made up of 2 monosaccharides.
- They are also called double sugars.
- The common disaccharides are;
(i) Maltose Glucose + Glucose
(ii) Sucrose Glucose + Fructose
(iii) Lactose Glucose + Galactose
- The chemical formula for all disaccharides is C12H22O11 .
- They are formed when two monosaccharides are condensed together.
- One monosaccharide loses an H atom from carbon atom number 1 and the other loses an OH
group from carbon 4 to form a bond called glycosidic bond.
- The reaction, involves the loss of water (H2O) and its called a condensation reaction,.
1. Maltose

- It is made up of 2 -glucose molecules

- A condensation reaction occurs between the OH - group on carbon number 1 of one alpha glucose
molecule and OH- group on carbon number 4 of another alpha glucose molecule.
- The products are MALTOSE + WATER (H2O)
- The bond formed is  - 1, 4 glycosidic bond

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H 2O

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 MALTOSE + WATER
 - 1, 4 glycosidic bond

OR

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2. Lactose
Its made up of galactose and glucose.

 -The products are LACTOSE + WATER

e.g.
- A condensation reaction occurs between the OH- group on carbon number 1 of  - galactose
molecule and OH- group on carbon number 4 of  - glucose molecule.
- The bond formed is  - 1,  - 4 glycosidic bond
 -The products are LACTOSE + WATER (H2O)

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 OR

 - 1,  - 4 glycosidic bond

3. Sucrose

- The products are SUCROSE + WATER (H2O)

DIAGRAM

Disaccharides are broken down by the process of hydrolysis which involves enzymes and water
molecules.
Hydrolysis breaks the glycosidic bonds

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e.g.

Polysaccharides
- They are polymers made up of many monomers which are joined by glycosidic bonds through
condensation reactions.
- The 3 common polysaccharides are;
1) Starch – energy storage molecule in plants.
2) Glycogen – energy storage molecule in animal cells, bacteria and fungi
3) Cellulose – it is a structural carbohydrate that gives strength in the plant cell walls.

The structure of starch

- It is a polymer made up of many -glucose molecules (monomers)
- These glucose monomers (molecules) are joined by glycosidic bonds
- It consists of two polymers namely amylose (30%) and amylopectin (70%)
Amylose
- It is a straight chain polymer made up of -glucose monomers joined by -- 1,4 glycosidic bonds

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- It is unbranched and with only 1,4 glycosidic bonds.
- Its formed by condensation reactions which involves loss of water molecules
- Each amylose is made up of 200 – 500-glucose molecules
- As the chain becomes longer, amylose becomes spiral and takes a helical shape. This makes it
more compact.
- The spirals / the helical shape is held in position by hydrogen bonds.
- The spirals have 6 monomers per turn.
- It consists of 30% of starch.

Amylopectin
- It is a branched polymer made up of  - glucose monomers joined by -- 1,4 glycosidic bonds
and  - 1, 6 glycosidic bonds.
- The  - glucose molecules are joined by -1,4 glycosidic bonds to form a straight chain and  - 1,
6 glycosidic bonds form branches.
- The branching occur every 20 -30 monomers
- This results in many terminal ends increasing surface area for enzymatic action. This makes
amylopectin to be easily broken down to release glucose monomers.
- Its formed by condensation reactions which involves loss of water molecules
- It consists of 70% starch.

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Note that
- The alpha1-6 glycosidic bonds cause branching
- A sports person is advised to take a carbohydrate meal rich in starch before tan exercise
because;
i) Presence of amylopectin which is branched provides glucose easily because it is readily broken
down
ii) Presence of amylose provides long term release of glucose molecules at a slow rate which are
broken down to release energy for a longer period.
iii) Break down of starch molecules releases many glucose molecules which are broken down to
release high amount of energy

Differences between amylose and amylopectin

Amylose Amylopectin
Short (200 -300 glucose molecules) Long (1,500 glucose molecules)
Straight chain / Unbranched Branched, hence has alpha 1,4 and alpha 1,6
glycosidic bonds
Contains hydrogen bonds No hydrogen bonds

Release glucose slowly Release glucose faster

Has alpha 1,4 glycosidic bonds Has alpha 1,4 and alpha 1,6 glycosidic bonds

Properties of starch
1. Its insoluble in water therefore, it does not affect the osmotic properties of the cell.
2. Its compact therefore, does not take much space.
3. Its inert therefore, it’s not involved in chemical reactions in the cell.
4. Its relatively large in size hence remains in the cell and does not diffuse out of cell in which it is
stored.
5. It contains many glucose molecules hence when hydrolysed, it releases many glucose molecules
which are broken down to release energy.
6. It contains amylopectin which is easily broken down to release glucose molecules when needed.
7. It contains amylose which releases glucose molecules more slowly for a long period of time.

The structure of glycogen

- It is a branched polymer made up of  - glucose monomers joined by -- 1,4 glycosidic bonds
and  - 1, 6 glycosidic bonds
- The  - glucose molecules are joined by -1, 4 glycosidic bonds to form a straight chain and  - 1,
6 glycosidic bonds form branches.
- The branching occur every 8 - 12 monomers
- Therefore, glycogen has many branches increasing surface area for enzymatic action. This
makes glycogen to be easily broken down to release glucose monomers.
- Its formed by condensation reactions which involves loss of water molecules

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Properties of glycogen
1. Its insoluble in water therefore, it does not affect the osmotic properties of the cell.
2. Its compact therefore, does not take much space.
3. Its inert therefore, it’s not involved in chemical reactions in the cell.
4. Its relatively large in size hence remains in the cell and does not diffuse out of cell in which it is
stored.
5. It contains many glucose molecules hence when hydrolysed, it releases many glucose molecules
which are broken down to release energy.
6. It has many branches therefore, it’s readily broken down to release glucose molecules when
needed.
Note
Amylopectin (starch) and glycogen are energy storage molecules, they are both branched and coiled
but glycogen is more branched, therefore stores more energy.

Functions of carbohydrates
1. Substrate for respiration (glucose).

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2. Energy stores (e.g. starch, glycogen).
4. Structural (e.g. cellulose, chitin in arthropod exoskeletons and fungal walls).
5. Transport (e.g. sucrose is transported in the phloem of a plant).
6. Recognition of molecules outside a cell (e.g. attached to proteins or lipids on cell surface
membrane).
LIPIDS

- They are fats and oils

- They are made up of the elements carbon, hydrogen and oxygen
- They are insoluble in water but soluble in organic solvents such as ethanol. Therefore, they do not
interfere with water based reactions in the cell
- The most common type of lipid is the triglyceride

Lipids can exist as fats, oils and waxes. Fats and oils are very similar in structure and both are
triglycerides.
Triglycerides

 Triglyceridesare one of the most important lipids

 The basic unit is glycerol and fatty acid.

Glycerol

Fatty acid
R – Represents a long hydrocarbon chain e.g. like the one shown below

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The long hydrocarbon chain can also be represented as;

One glycerol combines with 3 fatty acids to form a triglyceride (lipid molecule)

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  During formation of triglycerides, one of the OH- group of glycerol reacts with the
COOH (carboxylic group) of a fatty acid with removal of water molecules.
 The bond formed is called an ester bond and the reaction is a condensation reaction

Thus; Triglycerides are made of one molecule of glycerol and three fatty acids joined by ester bonds
formed by condensation reactions.

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 Structure of a triglyceride molecule

Types of Fatty Acids

 Fatty acids can be;

 Saturated fatty acids
 Unsaturated fatty acids

Saturated Fatty acid

 A saturated fatty acid has all carbon atoms in the hydrocarbon chain joined by single bonds
 Saturation refers to the amount of hydrogen in the molecule. A saturated fatty acid has no
double bond, hence, has the maximum number of hydrogen atoms bonded to the carbons,
and therefore is "saturated" with hydrogen atoms
 Due to lack of double carbon – carbon bonds in the hydrocarbon chain, there is no straining,
and therefore no kinking (bending). The intermolecular forces between molecules are
stronger and therefore, they have high melting point, above 40 0C and they remain solid at
both room and body temperatures.
 Lipids made of saturated fatty acids have high melting point hence solid at room temperature.

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Unsaturated Fatty acid.

 An unsaturated fatty acid has at least one or more carbon – carbon double bond within the
hydrocarbon chain.
 A fatty acid chain is monounsaturated if it contains one double bond, and polyunsaturated if it
contains more than one double bond.
 Where double bonds are formed, hydrogen atoms are removed from the hydrocarbon chain.
 Due to formation of carbon – carbon double bonds in the hydrocarbon chain, there is
straining, and therefore kinking (bending) occurs. This weakens the intermolecular forces
between the molecules lowering the melting points.
 The more the double bonds, the more the kinking and the lower the melting point.
 Therefore, they have lower melting point and they remain liquid at both room and body
temperatures.
 Lipids made of unsaturated fatty acids have low melting point hence liquid at room
temperature

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BASIS FOR
SATURATED FATTY ACIDS UNSATURATED FATTY ACIDS
COMPARISON

Saturated fatty acids contain single

Unsaturated fatty acids contain carbon
Meaning chain of carbon atoms with no double
chains with one or more double bond.
bond.

Hydrocarbon chain without double bond Hydrocarbon chain with one or more
Type of Bond
(only single bond). double bonds (C=C).

Physical appearanceSolid at room temperature. Liquid at room temperature.

Type of chain Straight chain. Bend chains at double bond.

Melting point Relatively higher. Relatively lower.

Fatty acids, they vary in the length of the chain i.e. number of carbons in the chain

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Phospholipids

 A phospholipids is a molecule made up of:

1 glycerol molecule bonded to 2 fatty acids linked by ester bonds and also bonded to
phosphate group by phospho-ester bond
 A phosphate group replaces one fatty acid chain. This makes this part of the molecule (the
head) soluble in water while the fatty acid chains remain insoluble in water.
 Due to this arrangement, phospholipids form play a major role in formation of cell membranes

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Cholesterol

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- This is a type of lipid made up in the liver from saturated fatty acids absorbed from food.
- The structure of cholesterol is

- In the cell membranes cholesterol has 2 major roles;

1. Control fluidity so that the cell membrane is not too fluid or too rigid
2. Provides the mechanical strength to the cell membranes. So, the cell membranes with little or
no cholesterol easily break down.
 In the cell membrane cholesterol occurs between the fatty acid tails

Functions of lipids
1. Storage - lipids are non-polar and so are insoluble in water. 2. High-energy store - they have a high
proportion of H atoms relative to O atoms and so yield more energy than the same mass of

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carbohydrate. 3. Production of metabolic water - some water is produced as a final result of
respiration.
4. Thermal insulation - fat conducts heat very slowly so having a layer under the skin keeps metabolic
heat in.
5. Electrical insulation - the myelin sheath around axons prevents ion leakage.

6. Waterproofing - waxy cuticles are useful, for example, to prevent excess evaporation from the
surface of a leaf.
7. Hormone production - steroid hormones. Oestrogen requires lipids for its formation, as do other
substances such as plant growth hormones.
8. Buoyancy - as lipids float on water, they can have a role in maintaining buoyancy in organisms

MASS TRANSPORT
Why we need a transport system

 Diffusion in single-celled organisms can occur directly between the external environment and
the cell cytoplasm, this is known as simple diffusion as it occurs only across the cell
membrane.
 Exchange of substances, such as oxygen for these organisms occurs very quickly as they
have a large surface area to volume ratio.
 Larger organisms, like humans, have a small surface area to volume ratio, meaning diffusion
would be too slow to supply all cells with the nutrients they need and this is why larger
organisms have mass transport systemsthat supply all cells with vital substances.

CIRCULATORY SYSTEM
- It includes blood vessels, the heart and the blood
BLOOD VESSELS
- Structure of blood vessels

- The mammalian circulatory system is comprised of the heart and three types of blood
vessels: arteries, veins and capillaries. Each blood vessel is adapted to its role in the
circulation of the blood.

1. ARTERIES

- Arteries transport oxygenated blood Away from the heart

- They thick walls containing muscles and elastic that expand and recoil with each heartbeat to
withstand the high pressure of the blood
- They have a relatively small lumen through which the blood passes
- Arteries contain no valves

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- Ateries split into smaller blood vessels called arterioles which split into capillaries
- They are lined with smooth endothelium to reduce friction and ease flow of blood
- Arteries have an external layer made of collagen fibers called tunica external / adventitia
- They also have a thick middle layer called tunica media made of elastic fibers, smooth
muscles and some collagen fibers
The elastic fibers stretch and recoil to maintain high B.P.

The smooth muscles contract and relax to allow the expansion of the lumen when blood flows
in pulses
The few collagen fibers offer strength and flexibility to withstand the high B.P in the arteries
- The artery also has an inner layer called tunica interna / intima. It consist of a single layer
of endothelium cells which are smooth and lines the lumen. This layer allow easy blood flow
with minimal resistance and reduces friction between the walls and the blood.
- The arteries have a narrow lumen to maintain high B.P

2. VEINS
- They consist of tunica externa, tunica media and tunica interna
- They tunica exerna consists of thinner collagen fibers than inarteriesas blood flows under low
pressure hence no risk of bursting the vein
- The tunica media consists of very little smooth muscles and elastic fibers. There is no need of
expansion of the lumen as blood does not flow in pulses and the lumen is wider
- The tunica interna consists of a single layer of endothelial cells which are smooth to allow
blood flow under minimal resistance and reduces friction between the blood and the wall
- They have a wider lumen which accommodates large volumes of blood and acts as a blood
reservoir due to the low blood pressure in the veins
- They have valves to stop back flow of blood as the blood is under low pressure

3. CAPILLARIES
- They have very thin walls to allow quick diffusion for fast exchange of substances between
the blood and the tissue fluid
- They have pores to allow exchange of substances. They have no collagen fibers, no elastic
fibers and no smooth muscles so that they can easily fit between calls and speed up diffusion
of substances across their walls
- They have no valves because their lumen is narrow
- They form a network to increase surface area for exchange of substances

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27
Vessel Structure Functional significance
1. Artery Tunica adventitia – collagen fibres Collagen fibres provide strength so
that arteries withstand high pressure
of blood without bursting. In addition,
they prevent overstretching of arteries.
Some elastic fibers. They stretch and recoil the arteries to
maintain pressure of blood
Tunica media
a) Smooth muscles They contract and relax to alter the
diameter of lumen to regulate blood
flow.
b) Elastic fibres

They stretch and recoil the arteries to

c) Some collagen fibres
Tunica intima (endothelium) –
maintain pressure of blood or
smoothen blood flow.
For strength to withstand high
pressure of blood.
It reduces friction between the walls

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 smooth, single layer of cells and the blood to ease blood flow
(squamous epithelium).
Narrow lumen To maintain high pressure of blood.
2. Vein Tunica adventitia – thinner collagen Blood is under low pressure hence
fibres vessels cannot burst.
Tunica media
a) Very little smooth muscle No pulse of blood so no alteration of
the diameter of the lumen
b) Very little elastic fibres No pulse of blood hence no
stretching and recoiling of veins
Tunica intima – (endothelium) – Reduces friction between the wall and
smooth, single layer of cells- blood to ease blood flow
squamous epithelium.
Wide lumen It acts as a blood reservoir to
accommodate large volume of blood
due to low blood pressure
Valves To stop the back flow of blood as it is
under low pressure
3. Capillaries Very thin wall (1 cell thick) Allows rapid exchange of substances
between blood and tissues i.e.
reduces diffusion distance
Pores Allows exchange of substances
Capillary network/bed Increases surface area of exchange of
substances
No valves Narrow lumen
No collagen fibres So that they can easily fit between
No smooth muscles and cells and speed up diffusion across
No elastic fibres their thin walls

STRUCTURE OF THE HEART

 The heart is comprised of 4 chambers: the left and right ventricles (which receive blood into
the heart), and the left and right atria (which pump blood out of the heart and into arteries to
be transported to the lungs or the body).
 Between the ventricles and the atria are the atrioventricular valves which prevent blood
flowing back from the ventricles and into the atria
 Between the ventricles and the arteries leaving the heart are the semilunar valves which
prevent backflow of blood from the arteries into the ventricles.

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 Mammals are described as having a ‘double circulatory system’, this is because the blood
flows through the heart twice in each circulation.
 The right and the left pumps of the heart are separated by a septum.
 The right side of the heart (right pump) receives deoxygenated blood from the body via the
vena cava, and it pumps it to the lungs for oxygenation and removal of CO 2 through the
pulmonary artery.
 The left side of the heart (left pump) receives oxygenated blood from the lungs through
pulmonary vein and pumps it to the body via the aorta.
 The blood in the left side of the heart does not mix with the blood in the right side of the
heart.
 The papillary muscles control movement of the atrioventricular valves (tricuspid & bicuspid).
 They contract to hold the tendinous chords tight
 The tendinous chords prevents the atrioventricular valves from being turned inside out when
the ventricles contract
 The carotid artery branches from the aorta and transports oxygenated blood to the brain
 The walls of the heart are made up of cardiac muscle (heart muscle)
 The cardiac muscles;
1. it contracts rhythmically without resting or fatigue.
2. It contracts on its own without being stimulated by a nerve (myogenic contraction),
 Atrial walls have thinner cardiac muscles while ventricle walls have thicker cardiac muscles.
However the left ventricle walls has thicker muscles than the right ventricle wall.

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CARDIAC CYCLE

 The movement of blood through the heart is carefully controlled by the contracting and
relaxing of heart muscles.
 Cardiac cycle refers to the sequence of events which take place to make a complete
heartbeat
 The periods of contraction are called systole. The periods of relaxation are called diastole.
 Regulation of the cardiac cycle is by the heart itself
 The heartbeat (cardiac cycle) is initiated in a specialised area of cardiac muscle in the right
atrium called the sinoatrial node (SAN) or the pacemaker. The SAN starts the waves of
depolarisation, which results in contraction.
 One cycle of systole and diastole make up one heartbeat [cardiac cycle]. One cardiac cycle
lasts about 0.8 seconds and produces the sound “lub dub“
 The cardiac cycle has three stages as follows:

1. Atrial systole
- The two atria contract pumping blood to the ventricles. This forces the atrio-ventricular valves
open and blood flows out of the atria and into the ventricles. Pressure in the atria is greater
than in the ventricles, so blood is forced out of the atria. It lasts about 0.1 seconds. The atrio –
ventricular valves are forced to open due to increased blood pressure in the atria and the

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 semilunar valves close because the ventricles are relaxed semilunar valves close because
the ventricles are relaxed

1. Ventricular systole
- The ventricles contract, causing the atrio-ventricular valves to close and semi-lunar valves to
open. Thus allowing blood to leave the left ventricle through the aorta and right ventricle
through the pulmonary artery.
- This is the contraction of the ventricles when they are filled up with blood. Its role is to pump
blood to the aorta and the pulmonary artery from the ventricles. It takes place 0.13 seconds
after the atrial systole and lasts for 0.3 seconds. The atrio – ventricular valves are closed to
prevent backflow of blood from the ventricles into atria and to build up pressure in the
ventricle. The semilunar valves are forced open and blood flows to the aorta and the
pulmonary artery. The closing of the atrio – ventricular valves produces the sound “lub”
2. Diastole
- During diastole, the atria and the ventricles relax and the atrio – ventricular valves open.
Deoxygenated blood flows from the right atrium to the right ventricle while oxygenated blood
flows from the left atrium to the left ventricle. Atrial and ventricular diastole take place at the
same time. Due to the relaxation of the ventricles, the semi-lunar valves close producing the
sound “dub “
The stages of the cardiac cycle relates to pressure changes

Pressure changes in the heart during a cardiac cycle

- During atrial systole, the atrial pressure is greater than the ventricular pressure because of
the refilling of the atria by the blood
- The blood flows to the ventricle and when the pressure in the ventricle exceeds the pressure
in the atria, the atrio – ventricular valves close
- The pressure in the ventricles continues to rise suddenly and forces the semi lunar valves
open
- Blood is pumped into the aorta and the pulmonary artery. The pressure in the aorta begins to
rise and when it exceeds the pressure in the left ventricle, the semi lunar valves close to
prevent backflow of blood to the left ventricle from the aorta
- Pressure in the left ventricle suddenly drops as the heart muscles relax
- The pressure in the aorta continues to reduce as elastic fibers stretch and then slightly
increases as elastic fibres recoil and continues to reduce as blood flows to the branches of
the artery

32
Thickness of the cardiac muscles
- The pressure generated by the cardiac muscles differ between the atria and the ventricle and
between the right and left ventricle
- The thicker the cardiac muscles, the more the contraction, the greater the pressure generated
and the longer the distance the blood flows

Thin cardiac muscles of the atria

- They are thick compared to those of the atria but less thick compared to those of the left
ventricle. The right ventricle pumps blood to a longer distance when they contract i.e. from the
atria to the ventricle.
- This requires less pressure to be generated thus the thin cardiac muscles of the atria

Thick cardiac muscles of the right ventricle

33
 - They are thick compared to those of the atria but less thick compared to those of the left
ventricle pumps blood to a longer distance compared to the atria but a shorter distance
compared to the left ventricle
- Therefore the right ventricle has more muscles than the atria. To generate pressure to pump
blood to the lungs but less muscles than the left ventricle
Thicker cardiac muscles of the left ventricle
- They pump blood to all body parts when the contract. They have thicker muscles that contract
powerfully to generate higher pressure to pump blood to all body parts through the aorta

NB; Therefore, the thicker cardiac muscles of the left ventricle function to
I] Generate higher blood pressure to pump blood to all body parts
II] To generate high pressure to overcome the effect of the elastic recoil in the aorta
III] To overcome combined resistance of multiple capillary network

HEART RATE

*It is the speed of a heartbeat measured by the number of contractions of the heart per minute
(Bpm-beats per minute)

Control of a heart rate

- Heart cells have intrinsic rhythmicity. It is maintained by a wave of electrical excitation initiated
by the Sino atrial mode [SAN]. However, heart rate can be controlled by the cardiovascular
center in the medulla oblongata
- The sympathetic nerve speeds up heart re
- Rate and the parasympathetic nerve slows the heart rate to normal

Factors that affect heart rate

1. Age – heart rate is high in children than in adults. Average heart beat in an adult is 70 beats
per minute and in children it’s about 120 per minute.
The high rate in children is due to various factors such as; they have high surface area to
volume ratio compared to adults therefore they need a faster transport of blood to supply heat
to compensate for the heat loss due to their large S.A. to volume ratio.
They also have a faster growth rate hence they need a faster transportation of glucose
oxygen for aerobic respiration
2. Stress- it rises levels of hormones like adrenaline thus increasing heart rate
3. Excitement – it also rises levels of hormones like adrenaline increasing heart rate
4. Stimulants – such as Nicotine and Caffeine increases heart rate
5. Exercise – during exercise, aerobic respiration is high and therefore cells need more glucose
and oxygen to provide more energy for the muscles to work

34
 The high rate of respiration leads to high levels of CO 2 in the blood. The heart rate increases
to supply O2 & glucose to the cells and to remove CO2

6. Receptors at the base of the aorta and the carotid artery there are receptors that respond to
high concentration of carbon dioxide. They respond by sending impulses to the cardio-
vascular center which sends impulses to the sympathetic nerve to the SAN in the heart rate.
Once the excess CO2 is removed, the parasympathetic nerve slows the heart rate back to
normal
7. Temperature – The higher the temperature, the higher the heart rate. High temperature
causes the blood vessels to dilate. This lowers the pressure within the blood vessels and
therefore the heart has to pump faster to maintain normal blood pressure.

BLOOD
- It’s the main transport medium in the body. However, there are 2 transport systems in humans
namely;
i] Cardio vascular system
ii] Lymphatic system

 Humans do not rely on diffusion for transport of substances in their body and that is why they
have a specialized transport system.
 Blood is involved in mass transport of substances because human have a small surface area
to volume ratio and therefore cannot rely on diffusion to meet the requirements of the
organisms.
 Small organisms such as amoeba have a large surface area to volume ratio and therefore
they rely on diffusion for absorption and movement of substances

Function of blood
1. It transports the requirements needed by body cells eg glucose, oxygen, amino acids
2. It transports waste products of metabolism from the cells such as urea, co 2
3. It transports hormones from endocrine glands to target cells
4. It forms part of the defence system of the body
5. It distributes heat throughout the body hence maintains homeostasis

Components of blood
- It consists of – White blood cells
- Red blood cells
- Platelets
- Plasma
Red blood cells [ RBCs]

35
  They are biconcave in shape in shape to increase area for transportation of gases
 They lack most organelles including the nucleus to increase surface area for transportation of
gases
 They contain haemoglobin, a protein that has the ability to bind respiratory gases particularly
oxygen to transport it to the body cells.

TRANSPORT OF GASES IN THE BLOOD

- Majority of the oxygen [around 98.5] in the body is transported when bound to haemoglobin.
About 1.5 of the O2 dissolves and is transported when dissolved in blood plasma
- At high concentrations, CO2 can also bind to haemoglobin

Haemoglobin

- Hemoglobin is composed of four iron-containing ring structures (hemes) chemically bonded to

a large protein (globin).
- Haemoglobin is a water soluble globular protein found in red blood cells, which consists of
two beta polypeptide chains (sub units), 2 alpha polypeptide chains (sub units), and 4 haem
groups. The four iron-containing ring structures (hemes) are chemically bonded to a large
protein (globin).

36
 - Each of the 4 polypeptide chains is bound to a haem group (Fe2 + ion) to which one oxygen
molecule can bind.
- This means each molecule of haemoglobin can carry 4 oxygen molecules
- The oxygen binds with haemoglobin to form oxyhaemoglobin, and can unbind when needed
in respiring cells and tissues.

Transport of oxygen and carbon dioxide

 The affinity of oxygen for haemoglobin (how easily oxygen loads onto haemoglobin) varies
depending on the partial pressure of oxygen, which is a measure of oxygen concentration.
 The greater the concentration of dissolved oxygen in cells the greater the partial pressure.
 Therefore, as partial pressure increases, the affinity of haemoglobin for oxygen increases.
 This means that oxygen binds to haemoglobin more readily. This occurs in the in the lungs.
 Binding of oxygen to the haemoglobin makes the entire haemoglobin molecule appear bright
red, thus oxygenated blood appears bright red while deoxygenated blood appears dark red.
 When the first oxygen molecule binds to haemoglobin, the haemoglobin changes its shape
(conformation) and this makes it easier for the other three oxygen molecules to bind.

37
  Binding of oxygen to haemoglobin depends on the partial pressure of oxygen (PO 2).
 When haemoglobin is exposed to a region where the PO 2 is high, e.g. in the lungs, oxygen
rapidly binds to haemoglobin.
 As oxygenated blood circulates, haemoglobin releases the oxygen molecules depending on
PO2.
 The dissociation of the first oxygen molecule causes the haemoglobin molecule to change its
shape making it easier for the other 3 oxygen molecules to dissociate.
 During respiration, oxygen is used up therefore the partial pressure decreases, decreasing
the affinity of oxygen for haemoglobin. As a result of that, oxygen is released from
haemoglobin in respiring tissues where it is needed.
 As oxygen diffuses into respiring tissues for respiration, carbon dioxide diffuses out and into
the capillaries.
 Here, in the low partial pressure of oxygen environment, carbon dioxide binds to
haemoglobin to form carbaminohaemoglobin . The deoxygenated blood returns to the lungs
where carbon dioxide unloads from haemoglobin, which binds to oxygen again.

Dissociation curves

 Dissociation curves illustrate the change in haemoglobin saturation as partial pressure

changes. The saturation of haemoglobin is affected by its affinity for oxygen, therefore in the
case where partial pressure is high, haemoglobin has high affinity for oxygen and is therefore
highly saturated, and vice versa.
 The relationship in blood between oxygen saturation (SO2) and partial pressure (PO2) is
described graphically by the oxygen–haemoglobin dissociation curve.
 SO2 represents the overall percentage of haemoglobin binding sites which are occupied by
oxygen. Each haemoglobin molecule can bind reversibly up to four oxygen molecules; in
addition, haemoglobin has the property that the binding of one oxygen molecule facilitates the
binding of subsequent oxygen molecules. Consequently, the affinity of each haemoglobin
molecule for oxygen increases until all four of its binding sites are occupied.
 At higher oxygenation, the curve flattens off as all the haemoglobin molecules approach full
saturation, resulting in the characteristic sigmoid (s-shaped) as shown below.

38
Theoretical oxygen–haemoglobin dissociation curve of a healthy individual with a normal blood
haemoglobin (Hb) concentration. The y-axis can be plotted as either % saturation or oxygen content
(concentration)

 Partial pressure is the pressure that would be exerted by one of the gases in a mixture if it
occupied the same volume on its own
 Thus, partial pressure of oxygen represents the pressure which oxygen would exert if it alone
occupied the volume.
Example
Since inspired air is 21% oxygen and atmospheric pressure is 760 mmHg (at sea level), the
partial pressure of oxygen is 0.21 x 760 mmHg = 160 mmHg. As air moves into the alveoli,
water vapour and carbon dioxide are added, and that reduces the partial pressure of oxygen
to about 100 mmHg in the alveolar gas.

Factors that affect affinity for oxygen by haemoglobin

 Saturation
- Saturation can also have an effect on affinity. After binding to the first oxygen
molecule, the haemoglobin molecule changes in shape and the affinity of
haemoglobin for oxygen increases, thus making it easier for the other oxygen
molecules to bind.
 Temperature.

39
 - High temperature reduces haemoglobin affinity for oxygen. This is because the bond
between the iron in the heme group and the haemoglobin protein chain denatures.
 pH
- A decrease in pH reduces the haemoglobin affinity for oxygen.

- This is because The H+ ions bind to the amino acids in the haemoglobin making it difficult
for oxygen to bind, resulting in haemoglobin releasing their oxygen molecules.
- The dissociation curve shifts to the right.

 Carbondioxide concentration (The Bohr effect)

- Haemoglobin’s oxygen binding is inversely related both to acidity and to the concentration
of carbon dioxide.
- Thus, the Bohr effect refers to the shift in the oxygen dissociation curve caused by
changes in the concentration of carbon dioxide or the pH of the environment.
- Carbon dioxide reacts with water to form carbonic acid, releasing H + ions, decreasing
blood pH. The H+ ions bind to the amino acids in the haemoglobin making it difficult for
oxygen to bind, resulting in haemoglobin releasing their oxygen molecules.
- The dissociation curve shifts to the right.

- Conversely, a decrease in carbon dioxide provokes an increase in pH, which results in

haemoglobin picking up more oxygen.
- Therefore affinity of haemoglobin for oxygen is also affected by the partial pressure of
carbon dioxide. Carbon dioxide is released by respiring cells therefore, in the presence of
carbon dioxide, the affinity of haemoglobin for oxygen decreases, causing oxygen to be
released.
- High carbon dioxide concentration in blood can lead to formation of
carbaminohaemoglobin, a compound formed when carbon dioxide reacts with
haemoglobin. This lowers the ability of haemoglobin to bind to oxygen.
 Carbon monoxide
- Haemoglobin reacts with carbon dioxide 200- 250 times more readily than with
oxygen forming carboxyhaemoglobin.
- Carboxyhaemoglobin is very stable and not easily broken down. The haemoglobin
binding site may remain blocked throughout the life cycle of that red blood cell.
-

40
The curve is shifted to the right by lower saturation, higher carbon dioxide concentration, greater
acidity (lower pH) and higher temperature.
This implies a reduction in the affinity of the blood hemoglobin for oxygen.

Fetal haemoglobin

- The haemoglobin present in foetuses has a different affinity for oxygen compared to
adult haemoglobin, as it needs to be better at absorbing oxygen because by the time
oxygen reaches the placenta, the oxygen saturation of the blood has decreased.
Therefore, fetal haemoglobin must have a higher affinity for oxygen in order for the
foetus to survive at low partial pressure.
- It consists of 2 alpha chains and 2 gamma chains.

Myoglobin

- Within the muscles of adults, there is an oxygen binding protein molecule called
myoglobin which has a higher affirnity for oxygen than haemoglobin in red blood cells.
- This allows oxygen to diffuse from haemoglobin in blood to the myoglobin in muscle
cells.
- The myoglobin also doesn’t release oxygen easily.

41
S

42
Sample Assessment Paper Question 7 (c)
7. (c) Fetal haemoglobin has a similar structure to adult haemoglobin. Fetal haemoglobin has two a
polypeptides and two γ polypeptides.The graph shows the percentage of each polypeptide
present in red blood cells in an individual before and after birth.

(i) Describe the changes in the percentages of polypeptides present in red blood cells. Use the
information in the graph to support your answer. (3)

A description that includes the following points:

 a polypeptide increases to maximum by 6 months before birth and then stays constant at 50% (1)

 ß polypeptide rises slowly during pregnancy but then increases rapidly after birth (1)

 γ polypeptide increases to maximum by 6 months before birth and thendrops rapidly after birth (1)

Platelets

 They are fragments of larger cells known as megakaryotes.

 They lack a nucleus.
 They initiateblood clotting when blood vessels are damaged.

Blood clotting
Blood clots are formed to minimise blood loss from damaged vessels, and also to prevent pathogens
entering the bloodstream. Blood clots are important to preventing damage to the body, however when
they form on the inside of blood vessels, they can restrict blood flow through the vessel and cause a

43
blockage. This is known as thrombosis and can cause cardiovascular disease. Blood clots are
formed as follows:

- Its clotting process is stimulated when there is damage to a blood vessel.

- Damage causes collagen fibres to be exposed in the vessel.
- Platelets rapidly stick to the exposed collagen fibres and these platelets release a clotting
factor called thromboplastin / thrombokinase (enzyme) that starts the cascade.
- In the presence of calcium ions and vitamin K, thromboplastin catalyses the conversion of
prothombin (inactive plasma protein) to an enzyme called thrombin (an active plasma protein).
- Thrombin (enzyme) catalyses the conversion of fibrinogen (soluble plasma protein) into fibrin
(insoluble plasma protein).
Fibrin forms a mesh that traps blood cells and platelets to form a blood clot

 Platelets become exposed to air or come into contact with the collagen fibres in a damaged
blood vessel wall and change shape from flattened discs to spherical shapes with thin
outward projections which form a temporary plug by clumping together.
 The platelets release clotting factors such as thromboplastin (thrombokinase) and serotonin.
 Thromboplastin in presence of calcium ions catalyses conversion of prothrombin to thrombin.
 Thrombin enzyme catalyses the conversion of fibrinogen to insoluble fibrin, whose strands
form a mesh, trapping red blood cells and platelets resulting into formation of a clot.
- Special proteins in the structure of platelets contract making the clot tighter and tougher.

NB:
Blood clotting process also involve other factors such as;

a) Clotting factor VIII – lack of this factor causes haemophilia A

b) Clotting factor IX - lack of this factor causes haemophilia B
c) Von Willebrand factor – it makes platelets stick to themselves and to the wall of the
injured blood vessel. It also acts as a carrier protein that carries clotting factor VIII. Lack
of this factor causes Von Willebrand factor diseases.

Questions
1. Suggest two differences between fibrinogen and fibrin.
Fibrinogen is globular (spherical) and fibrin is fibrous.
Fibrinogen is soluble and fibrin is insoluble
They are of different sizes

Exam Question
5. There are many venomous (poisonous) snakes in the world. Many of the venoms from these
these snakes affect the blood clotting process.
*(a) Describe the blood clotting process. (4)

1. idea that there is a cascade of events (leading to blood clotting) ;

44
2. ref to thromboplastin (starting the cascade) 3. ref to conversion of prothrombin into
thrombin ;
4. idea that {thromboplastin /thrombin} is {an enzyme / a catalyst} ;
5. ref to conversion of fibrinogen into fibrin ;
6. ref to formation of mesh of {fibres / fibrin} ;7. ref to requirement of {calcium ions/ Ca2+
/ vitamin K} ;
8. ref to {platelets / blood cells} getting trapped (in the mesh) ;

b) Factor Xa is a clotting factor present in human blood.

An experiment was carried out to investigate the time taken for human blood
to clot in the presence of different masses of Factor Xa. The experiment was
repeated using snake venom in place of Factor Xa.
The graph below shows the results of these experiments.

(i) Using the information in the graph, describe the effect of the snake venom on the clotting time of
human blood. (3)
1. snake venom decreases the clotting time /eq
2. (overall) as mass of snake venom increases the clotting time decreases /eq ;
3. idea that only a very small increase (0.004) in mass causes very sharp drop in clotting time ;
4. concentrations above {0.004 /0.02} cause little change in clotting time / eq ;
5. credit correct use of manipulated figures ;

45
(ii) Suggest why the clotting time of the human blood with snake venom added was compared with the
clotting time in the presence of Factor Xa. (1)
idea of one of the following:

if the snake venom has similar effects as a known clotting factor an idea of its mode of action can be
worked out /
how deadly the snake is /compare to normal (clotting) process /
possible use as medication /
for research into antidotes / eq ;

(c) The component of the snake venom that affects blood clotting is an enzyme.
(i) Describe the structure of an enzyme. (3)
1. ref to an enzyme as a protein ;

2. ref to {3D / tertiary / globular} structure ;

3. ref. to named bonds (holding structure in
place) ;
4. between the R groups ;
5. ref to active site ;
6. idea of specificity of active site ;

(ii) Suggest how the enzyme in the snake venom could be involved in the blood clotting process. (2)
1. it is one of the enzymes /similar to one of the
enzymes, in the clotting process / eq ;

2. idea that has active site complementary to

one of the substrates ;
3. ref to it activating other enzymes ;
4. ref to effect on platelets ;

5. idea that it triggers the clotting process ;

Exam Question 4

4. Cocaine use increases the risk of a heart attack.

Cocaine also affects the levels of a number of blood components, including
von Willebrand factor and fibrinogen. These two components are involved in
blood clotting.
(a) The normal range for von Willebrand factor is 50 to 150 mg per cm 3

46
and for fibrinogen is 150 to 300 mg per cm3.
The graphs below show the effects of frequent and occasional cocaine use on the
mean concentration of von Willebrand factor and fibrinogen in the blood.

(i) Describe the effects of frequent and occasional cocaine use on the mean
concentrations of von Willebrand factor and fibrinogen in the blood. (3)

1. idea that frequent cocaine use results in

{higher / an increase in / eq } levels in both
blood components (compared to occasional
use) ;
2. correct manipulation of figures to
approximate the increase in levels of one of
the blood components ;
3. frequent use increases fibrinogen beyond
normal range / eq ;
4. idea that the levels of both the blood
components are within the range for normal
levels in occasional users ;

(ii) Using the information given, explain why conclusions cannot be made about the
effect of occasional cocaine use on the concentrations of these blood components.
(1)

47
1. the levels are given as a {range / not one level / blood components within normal level
range}

2. no indication of data analysis e.g. spread of data, statistics

3. no indication of number in {samples / study /

4. no indication of other variables / named variable / eq ;

(b) The diagram below shows two functions of von Willebrand factor.

Using the information in this diagram and your own knowledge of the blood
clotting process, suggest why frequent cocaine use could increase the risk of a
blood clot forming. (4)
1. idea that von Willebrand factor results in platelets sticking to {the endothelium /each
other} ;

2. reference to release of thromboplastin (from platelets) ;

3. (as a result) the blood clotting process is triggered / eq ;

4. credit one correct detail of clotting process ;

5. reference to more fibrinogen resulting in the clot {being larger / growing faster } ;

6. reference to von Willebrand factor making the platelets stickier ;

7. as a result of {platelet stickiness /platelets sticking together} the {clot grows faster /
blood flow is decreased / eq} ;

8. If the blood is flowing slower then there is an increased chance of blood clotting / eq ;

48
(c) It has been suggested that there is a correlation between the change in the
concentrations of fibrinogen in the blood and the increased risk of heart disease
due to cocaine use. Explain why this suggestion is valid. (2)
1. idea that a correlation is {a relationship between two factors / when one factor
changes another factor changes} ;

2. fibrinogen increases with (cocaine) use / eq ;

3. heart attacks increase with cocaine use / eq ;

4. idea that increased fibrinogen levels have not been shown to result in the increase in heart
disease ;

Negative effects of blood clotting

It may lead to heart attack

1. Angina
2. Stroke
3. High blood pressure
4. Atherosclerosis

- Blood clots in the cardio vascular system ae caused by

I) Chemicals in cigarette smoke
II) Damage to endothelial lining
III) Accidents
IV) Atherosclerosis

 Clot formation in the cardiovascular system (blood vessels and the heart) may lead to
cardiovascular diseases (CVDs).
 Formation of a blood clot inside the blood vessel is called thrombosis. This obstructs the flow
of blood through the circulatory system.
 A blood clot that forms due to blood clotting process and remains stationary in a specific part
of a blood vessel is called a thrombus
 A clot, or a piece of the clot, that breaks free and begins to travel around the body is known
as an embolus. It is capable of travelling along the bloodstream into a distance from its point

49
 of origin, until they reach a narrowing in an artery through which they cannot pass. When
stuck, they significantly reduce the blood flow to cells beyond the blockage.
- If an embolus ends up in the human brain, it most often results in a stroke. If an
embolus lands in the heart, there is a high probability of heart attack. If it ends up in
the lungs, it will cause pulmonary embolism.

Negative effects of blood clotting

It may lead to heart attack

5. Angina
6. Stroke
7. High blood pressure
8. Atherosclerosis

- Blood clots in the cardio vascular system ae caused by

V) Chemicals in cigarette smoke
VI) Damage to endothelial lining
VII) Accidents
VIII) Atherosclerosis

 Clot formation in the cardiovascular system (blood vessels and the heart) may lead to
cardiovascular diseases (CVDs).
 Formation of a blood clot inside the blood vessel is called thrombosis. This obstructs the flow
of blood through the circulatory system.
 A blood clot that forms due to blood clotting process and remains stationary in a specific part
of a blood vessel is called a thrombus
 A clot, or a piece of the clot, that breaks free and begins to travel around the body is known
as an embolus. It is capable of travelling along the bloodstream into a distance from its point
of origin, until they reach a narrowing in an artery through which they cannot pass. When
stuck, they significantly reduce the blood flow to cells beyond the blockage.
- If an embolus ends up in the human brain, it most often results in a stroke. If an
embolus lands in the heart, there is a high probability of heart attack. If it ends up in
the lungs, it will cause pulmonary embolism.

50
CARDIOVASCULAR DISEASES (CVDs)
These are the diseases of the heart and blood vessels.

1. Atherosclerosis
It may start with a damage to the endothelial lining in an artery.
Atherosclerosis is the narrowing and the hardening of arteries caused by the build-up of fibrous
plaque called an atheroma. Atheroma formation is the cause of many cardiovascular diseasesand
occurs as following:

 The endothelium which lines the arteries is damaged, for instance by accidents, smoking or
high blood pressure.
 This increases the risk of blood clotting in the artery and leads to an inflammatory response
causing white blood cells to move into the damaged area of the artery.
 The process of blood clotting occurs and a clot forms at that point.
 Substances in blood especially cholesterol and fatty deposits accumulate at the damaged
area of the artery forming an antheroma.
 Fibrous tissue and calcium build up around the antheroma forming a hardened plaque and
that area of the artery becomes less elastic and this s called arteriosclerosis. This may
weaken the wall of the artery, a condition known as aneurysm.
 Over time, white blood cell, cholesterol, calcium salts and fibres build up and further harden
the plaque.
 The build-up of fibrous plaque leads to narrowing of the artery and restricts blood flow thus
increasing the blood pressure which in turn damages the endothelial lining further and the
process is repeated.
 The antheroma may break off into the circulation stimulating further blood clotting at that
point. The antheroma is then carried away in blood and may block another region of the blood
vessels.

51
Note;

 Atherosclerosis is caused by a build-up of fatty material in artery walls, which reduces the flow
of blood and therefore oxygen to the tissues.
 An atheroma is a build-up of cholesterol, fibres, dead muscle cells and platelets and is more
likely to develop upon damage to the artery wall by high blood pressure
 Aneurysm is the of the wall of an artery which produces a balloon like blood filled
swelling formed behind a plaque with a clot on its surface. Aneurysm frequently burst leading
to bleeding and therefore loss of blood in the region of the body.

2. Coronary heart disease (CHD)

- Disease that affects coronary artery which supply the heart muscle with oxygenated blood
transporting glucose and oxygen needed for respiration.
- When one of these arteries becomes blocked, the area of the heart muscle beyond the blockage
is cut off from oxygen and glucose supply, and it dies giving rise to heart attack or myocardial
infarction.
- When one of these arteries is partially blocked, it leads to angina pectoris.
- The two main reasons why blockages occur in the coronary arteries are:
a) Atherosclerosis – formation of plaque
b) Thrombosis – formation of clot that is usually formed on the rough surface of plaque
- So, there are two main forms of CHD (coronary heart disease);
a) Heart attack –
Due to complete blockage of a coronary artery.
It occurs as a sudden and severe chest pain due to death of heart cells, as a result of
blockage of the coronary artery starving the heart muscles of oxygen and glucose.
The symptoms of the heart attack are;
1. Shortness of breath

52
 2. Angina pectoris
3. Arrhythmia – the heart beats irregularly
4. Fatigue
5. Indigestion

b) Angina pectoris –
Due to partial blockage of a coronary artery.
Due to partial blockage, there is reduced blood flow to the parts of the heart muscles
beyond the blockage.
This makes the heart cells beyond the blockage to lack enough oxygen especially during
exercise.
The heart cells therefore carry out anaerobic respiration producing lactic acid.
The lactic acid produces a gripping pain in the chest.
The person feels breathlessness but the symptoms subside after exercise.
Other forms of CHD
- Overtime, CHD can weaken the heart muscle and lead to;
(i) Heart failure – condition in which the heart cannot pump enough blood to meet the body’s
requirements.

3. Stroke (cerebral infarction)

- Condition that affects carotid artery which supply the brain with oxygenated blood transporting
glucose and oxygen needed for respiration.
- When one of this artery becomes blocked, the area of the brain beyond the blockage is cut off
from oxygen and glucose supply, and it dies giving rise to stroke.
- It may also occur if an artery in the brain bursts and blood leaks into the brain tissue. The brain
tissue becomes starved of oxygen and dies. Strokes can be fatal or very mild and may affect
speech, memory and control of the body.
- The extent of damage depends on the size of the brain region that is affected.

4. Peripheral vascular disease (PVD)

- This is due to blockage or narrowing of arteries leading to periphery especially in the legs. This
leads to tissue death and then tissue decay also called gangrene.

5. High blood pressure (Hypertension)

It’s a condition in which there is a long term force of blood which is higher than normal against the
artery walls.

RISK FACTORS FOR CARDIOVASCULAR DISEASE

Risk is defined as the chance of something unfavourable occurring. There are a number of factors
that increase the risk for cardiovascular diseases, some within a person’s control and down to their
lifestyle choices, others outside of their control.

53
These factors include;

1. Genetics –
Certain genes can increase the risk, sometimes indirectly for instance by having genes for a
higher blood pressure or genes that result in faulty cholesterol metabolism. Family history of the
disease also increases your risk.
Studies show that there is some genetic tendency in some families and some ethnic groups to
develop CVDs.
These tendencies include;
 Tendency to have arteries that are easily damaged.
 Tendency to have high blood cholesterol due to faulty cholesterol metabolism
 Tendency to have high blood pressure
 Tendency to have mutations that affect high density lipoproteins to low density lipoproteins.

2. Diet –
Diets high in cholesterol, fatty foods, salts and carbohydrates have increased chances of build-up
of plaque on arteries in case of damage of endothelial lining.
 High intake of carbohydrates and fats may lead to increased weight and increased rate of
plaque formation.
 High intake of salts leads to retention of body fluids to balance osmotic properties. This
increases blood volume hence high B.P.

Antioxidants

 Diets with more antioxidants (vitamins) and soluble fibre decrease the risk of developing
CVDs.
 High intake of antioxidants e.g. vitamins E and C reduces the risk of developing CVDs and
vice versa.
 Antioxidants are compounds that donate electrons to free radicals to stabilise them, so that
these free radicals become non-toxic to cells.
 Natural antioxidants are mainly found in fruits and vegetables, marine plants and some sea
animals that eat marine plants.
 The most common dietary antioxidants are vitamins A,C E, beta carotene and lycopene –
found in tomatoes, water melon and papayas.
 Beta carotene is found in fruits.
Free radicals
 Free radicals are atoms or molecules that are highly reactive with the other structures of the
cell because they contain unpaired electrons.
 Free radicals cause damage to endothelium of blood vessels, by taking away their electrons
through oxidation. This is called free radical damage or oxidative damage.
 When free radicals oxidize endothelium it causes endothelial damage that triggers clot
formation or atherosclerosis.

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  One of the major sources of free radicals in the body is cigarette smoke.
 However free radical generating substances can also be found in the foods mainly fried foods,
drugs, medicines,, the air we breathe, alcohol, pesticides and air pollutants.
 Antioxidants lower the levels of low density lipoproteins lowering the risk of developing CVDs.

Oxidative stress

 Its an imbalance of antioxidants and free radicals of oxygen in the body. Free radicals of
oxygen are oxygen atoms with an uneven number of electrons, making it highly reactive and
meaning it can cause damaging chains of chemical reactions in the body.
 Antioxidants can donate electrons to make the oxygen radical stable, without making itself
unstable. It’s thought that this oxidative stress can contribute towards the cause of
cardiovascular disease, so the intake of additional antioxidants in the diet should help prevent
some cases of cardiovascular disease and at least lessen the risk.

Fibre
 Soluble fibre such as oat grain, barley, nuts, beans, lentils, peas, plums, pears, citrus fruits
e.g. lemons, oranges and limes, carrots and broccoli mix with water to form a substance that
traps dietary cholesterol so that it’s not absorbed into the blood stream.
 Since fibre is not absorbed, the absorbed cholesterol is passed out with faeces together with
the fibre. This removes cholesterol from the body and the body cells have to use the blood
cholesterol synthesized in the liver reducing the amount of circulating cholesterol. This
reduces blood cholesterol lowering the risk of developing CVDs.
 Fibre also traps bile so that it’s not absorbed into the blood stream.
Bile is released to aid in digestion of lipids. The bile acids are then reabsorbed back into the
bloodstream so they can be used again.
However, when trapped by fibre in the intestines, bile is broken down to cholic acid and the
cholic acid is further broken-down to a fatty acid that reduces cholesterol synthesis in the
liver.
 This results in an overall blood cholesterol level reduction.

Alcohol intake
 High alcohol intake raises levels of triglycerides circulating in the bloodstream that lead to
also block the lumen of arteries that carry blood to the heart. If coronary arteries are clogged
with fats, blood cannot flow freely, resulting in heart disease or stroke.
 Alcohol intake increases formation of low density lipoproteins increasing the rate of plaque
formation in case of damage to the endothelial lining
 Too much alcohol intake increases the blood viscosity affecting blood flow. This may lead to
high blood pressure and damage to the heart.
 Alcohol directly contributes to heart failure by damaging the heart muscle and arteries.

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 Long term use of alcohol leads to enlargement of the heart muscle. An enlarged heart no
longer works efficiently and fails to provide enough oxygenated blood to other organs of the
body.
 Long – term use of alcohol is associated with irregular heartbeat, sudden cardiac arrest and
stroke.

3. Age –
 Elasticity and width of lumen of arteries decrease with age. The heart has to pump harder
to overcome the resistance to blood flow due to the reduced lumen and reduced elasticity.
This causes blood pressure to rise. Increasing the risk of developing CVDs.
 Prevalence of CVD increases with age. Arteries weaken as age increases, therefore older
people are more likely to suffer from CVDs due to damage of endothelia lining of the
artery walls.
4. High blood pressure (hypertension) –
 This can damage the endothelia lining of the artery walls causing atherosclerosis that
lead to CVDs.

5. Smoking –
 Smoking damages the lining of arteries and can cause the formation of atheroma.
 Smoking increases the concentration of blood cholesterol, which is a risk factor, so
smokers have increased risk of developing a CVD than non-smokers.
 Tobacco smoke has substances that increases the risk of developing CVDs. These
include:
 Carbon monoxide – This Increases the levels of low density lipoproteins and
lower high density lipoproteins.
 Nicotine - Causes vasoconstriction reducing blood flow to the heart and
increasing blood pressure. Nicotine binds to proteins called nicotinic receptors
and this signals the smooth muscle in blood vessels to contract, making the
lumen of the blood vessels narrower. This can contribute to heart disease in two
ways--by reducing blood flow to the heart and by increasing blood pressure.
Constricted coronary arteries reduce the amount of blood that gets to the heart.
Constricted arteries throughout the body increase the blood pressure, which
forces the heart to pump harder to overcome resistance due to the narrowed
lumen.
 Chemicals in cigarette smoke cause damage to endothelium of blood vessels, by
taking away their electrons through oxidation as they are a source of free
radicals.
This causes damage to the endothelial lining of blood vessels increasing
chances of atherosclerosis.

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  There is a correlation between high levels of nicotine and inflammation as well as
damage of endothelial cells in blood vessels. Endothelial cells line blood vessels
throughout the body.
 Presence of nicotine in the brain, causes the release of adrenaline that causes
heart rate to increase, leading to higher blood pressure.
 Nicotine makes platelets ‘sticky’ increasing the chances of blood clotting.

6. Gender
 Under the age of 50 years, and men are more at risk of suffering from CVDs than
women. This is because oestrogen hormone gives women some protection from CVDs
before menopause. After menopause the risk in both sexes is about the same.
7. Obesity
 Being overweight strains the heart as it has to pump blood through he extra tissues. This
increases chances of developing high blood pressure and other CVDs.

8. Inactivity (lack of exercise) - has been linked with an increase in blood pressure
 Physical exercise at regular basis lowers risk of developing CVDs. This is because it
slows heart rate, lowers blood cholesterol and balances the high Density Lipoprotein: Low
Density Lipoprotein ratio.
9. Stress
 Stress causes increased heart rate hence increased blood pressure as the heart muscles
have to contract faster to maintain faster blood supply to the active cells. This may
eventually lead to development of other CVDs such as atherosclerosis due to the high
blood pressure.
 It may also lead to damage to the heart muscle.
 Studies show that people with little control over their own lives and work suffer more
stress are more likely to suffer from CVDs.

TREATMENT OF CARDIOVASCULAR DISEASES

 Antihypertensives

These are drugs that are used to lower blood pressure.

They include:
a) Diuretics
 They have effects opposite to those of antidiuretic hormone.
 They make the kidney tubules less permeable to water reducing water reabsorption
increasing the volume of urine.
 They increase the volume of urine produced by the kidneys and therefore remove the excess
fluids and salts in the body, hence lower the blood pressure.

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  Urine removes excess water and sodium out of the body. This lowers the volume of blood in
the bloodstream hence lower pressure on artery walls, reducing BP.
 In addition, loss of excess sodium causes blood vessels to open wider, further lowering the
blood pressure.
 They are generally effective on most patients and inexpensive.

Side effects of diuretics: muscle cramps, nausea, dizziness.

b) Beta blockers
 They interfere with the normal system of controlling heart rate by the Sino Atrial Node (pace
marker).
 They also reduce blood pressure by preventing the heart from responding to adrenaline
hormone.
 Beta blockers have similar shape to adrenaline, so, they bind to adrenaline receptors (beta-
adrenergic receptors ) on the cell surface membrane of the heart muscle cells. So, when
adrenaline is released it does not bind the heart cells hence no increase in heart rate.

c) Vasodilators
 They prevent the muscle cells in the tunica media of arteries from responding to the nerve
impulse hence no contraction. The arteries remain dilated, reducing blood pressure.

d) Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)

 They inhibit the enzyme called Angiotensin Converting Enzyme (ACE) so that it does not
activate a hormone called Angiotensin I into Angiotensin II.
 Angiotensin II hormone stimulates the constriction of blood vessels, raising the blood
pressure.
 ACE inhibitors are drugs with a similar shape to Angiotensin I. So, they bind to the active site
of the Angiotensin Converting Enzyme preventing Angiotensin I from binding. Angiotensin I is
therefore not converted to Angiotensin II.
 Angiotensin II is not therefore synthesized and the arteries remain dilated; hence reducing
blood pressure. They are active site directed Inhibitors.

e) Calcium channel protein blockers

 They block the calcium channels proteins in the muscle cells in the tunica media of arteries.
 This prevents contraction of the muscle cells so that arteries do not constrict and this lowers
blood pressure.
 For blood vessels to contract, calcium ions to enter the muscle cells to cause contraction.
 Calcium channel blockers attach to receptors of the muscle cells so that the chemical signal
that stimulates the opening of the calcium channel proteins is blocked.

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  Calcium ions therefore do not enter the muscle cells to cause contraction and therefore the
artery remains dilated, lowering the BP.

f) Sympathetic nerve inhibitors

 Sympathetic nerve increases heart rate and it leads to constriction of some arteries raising
blood pressure.
 Sympathetic nerve inhibitors prevent this nerve from sending impulses to the heart hence
heart rate is not increased.
 They also prevent this nerve from sending impulses to the arteries hence keep all arteries
dilated lowering blood pressure

Side effects of antihypertensives

a) Dizziness due to rapid lowering of blood pressure
b) Swelling of ankles
c) Constipation
d) Nausea
e) Muscle cramps
f) Abnormal heart beats
Risks of using antihypertensives
 If not monitored, blood pressure may fall too low leading to low metabolic activity, less heat
distribution and eventually death.

Risks of using antihypertensives

They reduce blood pressure hence reduce damage to organs like the brain, heart, lungs, and arteries.

3. Statins

 Also known as HMG-CoA reductase inhibitors,

 Plant statins are drugs that lower blood cholesterol level.
 They block the enzyme in the liver responsible for production of cholesterol and low density
lipoproteins.
 Statins have an active site that binds to enzymes like HMG-CoA reductase which is involved
in the synthesis of cholesterol.
 This interferes with the process cholesterol synthesis lowering cholesterol levels hence,
reducing the amount of cholesterol in circulation.
 Statins also improve the balance between LDLs and HDLs as well as generally reduce
inflammation in case of damage of endothelial lining.
 The side effects of statins include:-
a) Joint problems
b) Liver problems
c) Kidneys problems

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 d) Constipation
e) Respiratory cancer
f) Reduced vitamin intake

4. Anticoagulants

 These are drugs that helpprevent blood clot formation or prevent a clot that has formed from
enlarging by breaking it up.
 This is the treatment given when someone is at risk of getting heart attack or stroke due to
high blood pressure and high blood cholesterol level.
 Such people, in addition to antihypertensive drugs and plant statins, they are given drugs to
prevent clotting in the artery.

Anticoagulants are classified into three groups:

1. Inhibitors of synthesis of clotting factors

 These anticoagulants inhibit the production of clotting factors in the liver, e.g. warfarin –
which inhibits synthesis of prothrombin.

2. Inhibitors of thrombin.

 These drugs interfere with blood clotting process by blocking the activity of thrombin. They
include heparin and lepirudin and heparin.

3. Platelets inhibitory drugs)

 These drugs interact with platelets, to block them from aggregating or adhering to one
another or sticking to one another by making them less sticky so that they do not form clots.
Examples include asprin, and clopidogrel.

NB: The Liver synthesises many blood clotting factors such as :

i) Factor I (Fibrinogen) ii) Factor II (Prothrombin) iii) Factor IV
iv) Factor V v) Factor VI vi) Factor VII

Risk of using anticoagulants

1. Some like the platelet inhibitory drugs irritate the stomach lining, causing bleeding in the
stomach.
2. They may also lead to stomach ulcers
3. Since they are blood thinners they may lead excessive bleeding in case of an injury.

Treatment of angina pectoris

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 1. Use of medical drugs to dilate coronary artery and / or its branches for sufficient oxygen
supply to the heart cells.
2. If the condition is serious, a heart bypass surgery (Coronary artery by-pass operation) is
done.
This involves removing an artery of another body part or use of an artificial artery like
structures to bypass the blocked region.
3. Heart transplant
4. Coronary angioplasty
5. Insertion of a coronary stent
 Agioplasty is a technique that involves widening the narrowed artery lumen mechanically
 A coronary stent is a tube-shaped device placed in the coronary arteries that supply blood
to the heart, to keep the arteries open in the treatment of coronary heart disease.

Coronary angioplasty procedure is used to open clogged heart arteries. Angioplasty uses a tiny tube
that is inserted in a blocked blood vessel to help widen it and improve blood flow to your heart.
Angioplasty is often combined with the placement of a small wire mesh tube called a stent. The stent
helps maintain the artery open, decreasing its chance of narrowing again. Angioplasty is also often
used during a heart attack to quickly open a blocked artery and reduce the amount of damage to your
heart.

Treatment of stroke
The quick treatment for stroke that may help the patient to survive is giving clot bursting drugs
such as aspirin.

SIGNIFICANCE OF BLOOD CHOLESTEROLLEVELS TO HEALTH

 Cholesterol is a lipid synthesised in the liver from saturated fatty acids.

 Cholesterol, being a lipid, it has low solubility in plasma and it’s therefore largely transported
when combined with molecules called lipoproteins.
 Thus cholesterol is transported in your body in high-density lipoproteins (HDLs) or low-density
lipoproteins (LDLs)
 A lipoprotein is made up of phospholipids and proteins and they play a major role in in
transport of cholesterol in blood.
 The lipid part of the lipoprotein enables it to combine with cholesterol
 There are two types of lipoproteins.

The major types of lipoproteins:

1. Low density lipoproteins

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  They are formed from saturated lipids and proteins.
 They contain less proteins and more lipids and therefore they are less dense i.e. LDL is larger
than HDL.
 Normal concentration of LDL is required to transport cholesterol from the liver to the body
cells.
 The liver is the primary organ that synthesises cholesterol in the body.
 The body cells have LDL receptors onto which the LDL bind to in order to enter these body
cells.
 When LDL concentration is high, the receptors on the cell surface membrane becomes
overloaded or saturated and the excess LDLs remains in the blood. This raises the blood
cholesterol level, and can lead to atheroma formation in case of damage to the endothelia
lining.
 They should be maintained at low levels.

2. High density lipoproteins

 They are formed from unsaturated lipids and proteins.
 They contain more proteins and therefore are denser as proteins are compact molecules. i.e.
HDL is smaller than LDL; it has more proteins, less cholesterol.
 They carry cholesterol from the body cell to the liver cells
 HDL transport cholesterol from the body cells including blood vessels back to the liver to
be broken down and excreted. This lowers circulating blood cholesterol and educes chances
of atheroma formation reducing the risk of CVDs.
 HDL removes excess cholesterol from the tissues and arteries, and returns it back to the liver
for recycling and removal from the body. This is known as “reverse cholesterol transport”.
 When HDLs carry cholesterol to the liver, they enter the liver cells without binding to the cell
receptors.
 HDL has a positive anti-oxidant effect, which helps protect blood cells and important
chemical messengers in the blood from being broken down.
 HDL is advisable to improve the health.

NB:

 Sources of blood cholesterol are:

1. Liver
2. Diet: associated with saturated fats from products like eggs, meat and dairy products
 During cholesterol synthesise in the liver, enzyme HMG-CoA reductase is involved. This is
the enzyme that plant statins interferes with to stop cholesterol formation reducing the risk of
developing CVDs.

ROLES OF CHOLESTEROL IN THE BODY

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 a) Synthesis of steroid hormones such as progesterone and testosterone
b) Synthesis of bile salts
c) Synthesis of some growth hormones
d) Regulating fluidity of the membranes and give strength to them.
e) Controlling permeability of the cell membrane.
f) Synthesis of vitamin D in the skin

 Cholesterol is important in the body, health problems arise when there is excess cholesterol.
 The higher the amount of LDLs the lower the amount of HDLs and vice versa.
 At puberty, in males, HDLs drop and LDLs increase which is thought to be the effect of
testosterone production.
 In females, oestrogen increases HDLs levels.

LDLs HDLs

Made from saturated lipids Made from unsaturated lipids

Bind to receptors on the cell surface Do not bind to receptors on the cell surface
membrane which can become saturated membrane.
leaving LDLs in circulation

Transport cholesterol from the liver to the Transport cholesterol to the liver cells where it is
body cells broken down and excreted.

Excess LDLs are associated with Reduce chances of development of CVDs

development of CVDs

OBESITY INDICATORS

 Obesityis one of the causes of cardiovascular disease.

 Being aware you are overweight or obese can help encourage a change in diet and increase
in exercise to reduce the risk of CVDs.

Two obesity indicators are;

a) Body Mass Index (BMI)
b) Waist to hip ratio

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Body mass index (BMI)

BMI is a value calculated using the following equation:

Body mass in Kilograms ÷ (body height in metres)²

Body mass(kg)
- i.e. BMI =
Height ∈meters squared

The value generated is compared to a chart which classifies you under the following:
- Under 18.5 - underweight
- 18.5 - 25 - normal
- 25 - 30 - overweight
- Over 30 - obese

Example, mass of a person is 60kg and height is 1.5m

BMI = 60 = 26.6 kgm-2 - normal weight
2
(1.5)

Limitations of Use of BMI

a) It does not give the difference in BMI caused by bones, muscles and fats e.g. the weight of
large muscle will be treated as the weight of fat by BMI.
b) It does not explain why some athletes have high BMI and yet healthy
c) It underestimates body fat in older people who have lost a lot of their muscles hence
incorrect with advanced age due to reduced body mass.
The effects of obesity;
a) Risk factor for Type II Diabetes
b) Risk factor for CVD
c) High blood pressure, that lead to development of CVD
d) Joint problems including arthritis due to damage of cartilage.

Waist to hip ratio (WHR)

 WHR is another way to view if someone is overweight and can also be used to view their risk
of developing certain diseases.
 The waist measurement is taken above the hip bone and below the rib.
The hip measurement is taken around the widest part of the hips.
 One is classified as obese as a male the value is greater than 0.9 and as a female if the is
value greater than 0.85.
 For men, it should not be more than 0.90 and for women, it should not be more than 0.85.

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  Waist to hip ratio is the best indicator of obesity compared to BMI because it only considers /
measures fat.

BASAL METABOLIC RATE (BMR)

It’s the minimum amount of energy required by the body at rest to maintain body processes per day
i.e 24 hours. Such body processes are; breathing, processes that maintain body temperature constant
and heart rate
- Its affected by;
a) Age
Its higher in children than adults because they need energy for growth
b) Gender
Its higher in males than females because males have more muscles that need more
energy to maintain.
c) Body mass – Its higher in overweight people because they have extra tissue.
d) Level of activity
Its higher in active people

PHYSICAL ACTIVITY LEVEL (PAL)

In addition to BMR, energy is needed for physical activity.
BMR X PAL = EAR (Estimated Average Requirements for energy)
Therefore, PAL reflects physical activity.
In an average man in UK, Physical Activity Level (PAL) 1.4.
 Intake of energy should be balanced.
- Energy input should be equal to energy output/expenditure to prevent underweight or
overweight occurrences.
- When one consumes more energy than the body requires, it leads to overweight or obesity
and when one consumes less energy than the body’s requirements it leads to underweight.

POPULATION STUDIES ON RISK FACTORS

 Risk is the probability / chance of something unfavourable occurring.

Two types of risks are;

a) Perceived risk - It’s a subjective judgment made on the probability of an event occurring.
b) Actual risk - It’s an actual probability of an event occurring.

 Statistical chance of something occurring can be supported using data obtained by scientific
research

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  Perceived risk varies from person to person and is based on different factors, as a result of
that, the perceived risk can vary greatly from the actual risk, thus leading to underestimating
or overestimating the probability of occurrence of an unwanted event or outcome.

A risk factor shows a correlation or a causation relationship between an event or the risk and the
outcome.

Correlation

It’s a relationship or a link between two variables which, does not prove that the factor is the cause of
the outcome. However, the factor and the outcome change in a similar direction e.g. as one variable
increases, the other also increases.

Values can have a correlation, but that does not mean they cause each other. For instance, the
average temperature in 2 places both increase over 2 months, this is correlation, because one has not
caused the increase in the other, so there is no causation.

Further research must be done to determine the actual cause.

Causation
This is when one variable causes another to change.
E.g. an increase in cholesterol levels can cause an increase in plaque formation because the
cholesterol is directly deposited on damaged endothelial lining.

Epidemiology
 Epidemiology is the study of risk factors for health in a population.
 There are two kinds of epidemiological studies;
a) Cohort studies
b) Case-control studies
Cohort studies
 The main features are:-
 Large number of people is followed.
 It takes long period of time.
 Individuals are monitored to see if they develop the condition under study while they
are exposed to risk factors under investigation.
 Those that develop the condition are placed in a different group from those who do
not develop the condition.
 Various risk factors that the subjects (people) have been exposed to are looked into.
 Correlations and causations are looked for.
Disadvantages

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a) Large number of people is observed hence takes time and resources
b) It takes long period of time and so results are not immediate
c) It is expensive
d) Due to the long period of time, some subjects may withdraw, move, migrate or die.

Case-control studies
The main features are:-
 A group of people with the condition (case) is compared with a group that does not have
(control)
 Their past history is investigated to identify factors leading to one group having the disease
and the other not.
When epidemiological studies are carried out across the countries;
 Large number of subjects are used to increase the chances of getting subjects with the
condition
 The same number of subjects is used in all counties. This is because different countries have
different population sizes and therefore for validity, the number of subjects per country should
be equal.
Advantages
 It’s faster hence results are available faster
 Data can be collected face to face or using questionnaires therefore its cheaper as few
staff are involved

Disadvantages
 Relatively high level of literacy is required especially when questionnaires are used.
 Participants may likely give inaccurate information as they may not take the study
seriously.
 Participants might give answers that show a healthier lifestyle than they live / have.
 Some participants may not accurately remember their past history.

A good epidemiological study should have the following features;

 Sample should be representative to avoid
 Sample size should be large. The larger the sample size, the more valid the results are.
 Variables / factors such as age should be controlled when selecting cohort or case control
groups.

EVALUATING STUDIES

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In order to make conclusions from scientific studies they must have been carried out appropriately to
avoid bias and to be representative of the whole population.

 Sample selection must be done randomly to avoid bias,

 The study must have a sample size that is large enough to be representative of the whole
population
 The samples must be sampled across different areas. For instance a nationwide study cannot
sample from one city only or an international study cannot sample from one country only.
 The data should have values that are read as accurately as possible and the most accurate
equipment available should be used.
 All other factors that affect the outcome should be controlled
 The results should be reliable – reliability is increased by carrying out repeats to calculate the
mean and indicating variability by drawing range bars or error bars.
- Range bars are drawn using the highest and the lowest values from the raw data.
- Error bars are drawn using the standard deviations calculated.

TOPIC 2 – MEMBRANES, PROTEINS, DNA AND GENE EXPRESSION

GAS EXCHANGE

Exchange surfaces
Multicellular organisms require gas exchange systems in order to obtain sufficient oxygen for
respiring cells, and to expel the carbon dioxide produced by these cells. In order to maximise the rate
of exchange of substances, gas exchange surfaces are adapted to have a:

1) Large surface area to volume ratio - the larger the ratio, the greater the surface area for the
organism to carry out exchange, so a faster transfer of substances across the surface.
2) Short diffusion distance - a short distance for substances to move across means they move
faster.

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 3) Steep concentration gradient - a large difference in concentrations between 2 areas means
diffusion of particles from an area of high concentration to an area of lower concentration
occurs faster.

The mammalian lung

 When we breathe, air enters the mouth, passes into the trachea which splits into 2 bronchi;
one on the left side and one on the right side of the body.
 Each bronchus branches out into smaller bronchioles which end in tiny air sacs called alveoli
where gas exchange takes place.
 Deoxygenated blood flows into the alveoli, where carbon dioxide diffuses out of the capillary,
through the alveolar membrane and into the surrounding air, down a concentration gradient.
Oxygen moves in the opposite direction from the surrounding air and into the blood steam,
making the blood oxygenated.
 The extensive branching of vessels in the lungs means there are many

Properties of the mammalian gaseous exchange surface / adaptations of the alveoli to gaseous
exchange

1) The alveoli are numerous to increase surface are for gaseous exchange - (over 300 million in
an average adult) –
This gives them a very large surface area which increases the rate of diffusion of oxygen into
the blood, and carbon dioxide out of the blood.
2) They have a rich blood supply from surrounding capillaries which maintains a steep
concentration gradient between the blood in the capillaries and the air entering the lungs,
which again increases the rate of diffusion.
3) Alveoli also have a moist outer lining, allowing gases to dissolve and move across their
membrane faster.
4) Alveoli have a wall of only one cell thick and pores in the endothelium, this creates a short
distance for the gases to travel over so they can diffuse quickly.
5) The alveoli wall secretes a lung surfactant that lower the surface tension of water for gases to
dissolve faster.

FICK’S LAW

The rate of diffusion is proportional to the surface area multiplied by difference in concentration,
divided by the length of diffusion pathway.
Fick's Law states that the rate of diffusion of a gas across a permeable membrane is determined by
the chemical nature of the membrane itself, the surface area of the membrane, the concentration
gradient of the gas across the membrane, and the thickness of the membrane.

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 A measure of the ease with which an ion or molecule can cross a unit area of membrane expressed
per second is called permeability constant.
Permeability constant varies with the characteristics of the membrane and those of the solute.
The permeability constant is different for each organism.
 The rate at which gases can diffuse across membranes is an important aspect of respiratory
physiology as oxygen and carbon dioxide must cross the alveolar membrane during the gas exchange
process.
Rate of diffusion = Permeability constant X Surface area X Concentration gradient
Thickness of the membrane
(Distance the gas travels)

Note;

 Rate of diffusion is directly proportional to the surface area, therefore, as surface area
increases the rate of diffusion increases.
 Rate of diffusion is directly proportional to the difference in concentration gradient, therefore,
as the concentration gradient increases, the rate of diffusion increases.
 Rate of diffusion is inversely proportional to the thickness of the gas exchange surface,
therefore as the thickness increases the rate of diffusion decreases.

Question
The cell membrane has a thickness of 10 nm.
Describe what happens to the rate of diffusion of oxygen into the cell if the thickness changes
to 20 nm.
The rate of diffusion will halve.
Example
A section of alveolar epithelium has a surface area of 2.2 µm2 and is 1.0 µm thick. The permeability
constant of the alveolar epithelium for oxygen is 0.012 s–1. The concentration of oxygen on one side
of the epithelium (C1) is 2.3 × 10–16 mol µm–3 and the concentration of oxygen on the other side (C2) is
9.0 × 10–17 mol µm–3. To calculate the rate of diffusion of oxygen across the alveolar epithelium, you
need to put these values into the equation;

Rate of diffusion = 0.012 X 2.2 µm2 X (2.3 × 10–16 mol µm–3 - 9.0 × 10–17 mol µm–3)
1.0 µm

= 3.7 X 10 -18 mol-2 s-1

NB: There are different ways of writing Fick’s Law as an equation. No matter what equation given in
the exam, you’ll also be given all the information you need to use it.

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For Example sometimes the permeability constant may not be given;
Using the above example;

A section of alveolar epithelium has a surface area of 2.2 µm2 and is 1.0 µm thick. The concentration
of oxygen on one side of the epithelium (C1) is 2.3 × 10 –16 mol µm–3 and the concentration of oxygen
on the other side (C2) is 9.0 × 10–17 mol µm–3. To calculate the rate of diffusion of oxygen across the
alveolar epithelium, you need to put these values into the equation;

Rate of diffusion = Surface area X Concentration gradient

Thickness of the membrane
(Distance the gas travels)

Rate of diffusion = 2.2 µm2 X (2.3 × 10–16 mol µm–3 - 9.0 × 10–17 mol µm–3)
1.0 µm
= 3.08 X 10 -16 mol-2 s-1

CELL MEMBRANES

 All cells and most organelles are surrounded by a partially / selectively permeable membrane
composed of phospholipids with protein molecules between the phospholipid molecules.
 The main function of the membrane iscontrolling the movement of substances in and out of
the cell/organelle.
 The membrane also contains receptors for other molecules, such as hormones, and enables
adjacent cells to recognise one another and to stick together.

Structure of the cell membrane

Fluid Mosaic Model

 The fluid mosaic model is the currently accepted model / theory used to explain the structure
of the cell membranes.
 The model suggests that the membrane is a ‘fluid’ structure made up of mainly phospholipids
that move within the membrane or slide past each other, with a mosaic of different proteins
randomly arranged.
 Due to the fluidity of the phospholipid bilayer it allows molecules to move freely within it.
 The cell membrane also contains a ‘mosaic’ of proteins of varying shapes and sizes.

Thus;
The membrane is fluid because the phospholipids move around the membrane making the
cell membrane to be constantly in motion and the membrane is mosaic because different
types of proteins are randomly arranged among the phospholipids in the membrane.

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  Cholesterol molecules are also found in the bilayer, these give the membrane stability and
regulate its fluidity.

The main structure of a membrane is the phospholipid bilayer - 2 rows of phospholipids.

 A phospholipid is a lipid made up of one glycerol, two fatty acids and one phosphate group.

 A phospholipid is made up of one glycerol, two fatty acids and one phosphate group
 The phosphate groups are hydrophilic (water loving). So they orientate / face towards the
water molecules in the cytoplasm of the cell as well as towards the tissue fluid surrounding
the cell.
 The fatty acid chains are hydrophobic (water hating), so lie in between the 2 rows of
phosphate heads
 This arrangement results in formation of a bilayer.
 The phospholipids contain saturated and unsaturated fatty acids. This allows for the control
of the fluidity of membranes, which is useful, for example, in maintaining membrane fluidity at
low temperatures.

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 The fatty acid chains are non-polar.
 Therefore the phospholipid bilayer allows small non-polar molecules like carbon dioxide and
oxygen as well as fat soluble organic molecules to pass through the phospholipid bilayer.
While large and/or polar/ionic substances, like water, cannot pass through the phospholipid
bilayer. They have to move through channel proteins, since they aren’t soluble in the fatty
acid tails.
 The membrane is more fluid when it contains more unsaturated fatty acids.

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The cell membrane also consists of proteins.
There are different kinds of proteins in the cell membrane.

- These proteins include;

(i) Peripheral protein - These are attached to the surface of phospholipid bilayer.
(ii) Integral protein - These are embedded in the phospholipid bilayer. Integral proteins are
permanently attached to the membrane.
Integral proteins include:
- Those embedded in the inner or outer phospholipid layers i.e. they span part of the bilayer.
These may function as enzymes that catalyse reactions linked to the cell surface
membrane e.g. sucrose molecules in the cell surface membrane of intestinal cells.
- Trans-membrane proteins that penetrate / span through the phospholipid bilayer so that they
are exposed at both sides.
Some trans-membrane proteins function as channel proteins which are either fixed proteins
that form pores or gated channels proteins that open or shut depending on the conditions of
the cell.
Some trans-membrane proteins function as carrier proteins that use energy in form of ATP to
move molecules across the membrane.

The cell membranes also has cholesterol.

The cholesterol molecules are found in the bilayer.

 It helps separate the phospholipids so that the fatty acid tails do not come together.
 This give the membrane mechanical strength / stability and regulates its fluidity.
 With little cholesterol, the membrane more fluid and with much cholesterol, the membrane
rigid.
When too rigid, materials may leak out of the cell i.e. the membrane become too permeable –
thus cholesterol affects membrane permeability.

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 The cell membrane also consist of glycolipids.

- A Glycolipid is made up of a lipid and a carbohydrate.

- It is found only on the outer part of the phospholipid bilayer.
Their functions are:-
(i) Some act as cell to cell recognition sites
(ii) Some play a role in cell to cell adhesion
(iii) Act as receptors /such as hormone receptors / hormone binding sites.
(iv) Acts as antigens
In addition the cell membrane is made up of glycoproteins.
A glycoprotein is made up of protein and a carbohydrate.
Their roles are;
i. Some act as cell to cell recognition sites
ii. Some play a role in cell to cell adhesion
iii. Act as receptors /such as hormone receptors / hormone binding sites.
iv. Acts as antigens

- Therefore the structure of the cell surface membrane is made up of:

1. Lipids;
(i) Phospholipids
(ii) Cholesterol
(iii) Glycolipids
2. Proteins;

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 (i) Peripheral proteins
(ii) Integral proteins
(iii) Glycoproteins

Membrane proteins perform a variety of functions

 The glycoproteins allow cells to identify each other and interact, for example, proteins
involved in immune responses. Others form proteins that relay signals between the cell's internal
and external environments.
 Transport proteins move molecules and ions across the membrane.
 Membrane enzymes catalyse reactions linked to the cell membrane.

3. Carbohydrates;
(i) Glycoprotein
(ii) Glycolipid
- This means that the carbohydrates occur either in association with proteins (glycoproteins) or lipid
(glycolipids)
- Glycoproteins and glycolipids are collectively called glycocalyx

Role of fluidity of membranes

The importance of fluidity of the membranes are:

(i) Allows membrane to change shape i.e. during phagocytosis, active transport and facilitated
diffusion.
(ii) Allows vesicles to be pinched off from the membrane e.g. during endocytosis.
(iii) Allows vesicles to fuse with the membranes during exocytosis or membranes to fuse with
other membranes.

Evidences that support the fluid mosaic model

1. To support that the membrane is fluid;
a) Membranes of different cells join to form one continuous membrane when the cells fuse
together.
b) When cells fuse, some proteins change in position showing that the proteins of the two cells
intermingle randomly.
c) When a membrane of a cell is punctured with a needle, the membrane seals off.
d) Vesicles pinch off from membranes e.g during exocytosis.
2. To support that the membrane is a phospholipid bilayer;
Phospholipids at an air/water interface form one layer/monolayer with the phosphate heads in
the water and fatty acid tails in the air meaning that the phosphate heads are hydrophilic while

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 the fatty acid tails are hydrophobic. So, the phospholipids form a bilayer with the hydrophobic
tails hidden away from the water molecules in the cytoplasm and the tissue fluid.

3. To support that phospholipids form a large part of the cell membrane;

When the cell is supplied with both lipid soluble and polar substances, the lipid soluble
substances through the membrane easily than other substances showing that a large part of
the membrane is made up of lipids through which they pass through.
4. To support that proteins play a transport role across the membrane;
Large polar/charged molecules and ionic molecules can only cross the membrane if
channel proteins and/or carrier proteins are present.

TRANSPORT OF SUBSTANCES ACROSS THE CELL MEMBRANE

 The movement of molecules through cell membrane depends on;

a) The properties of the molecule for instance
i. Its size
ii. Whether it is polar or nonpolar

b) The requirements of the cell.

Movement can be;

a) Passive (require no energy) or

b) Active (requires energy in form of ATP released from respiration).

There are several types of movement:

1. OSMOSIS

Osmosis is the movement of water molecules from a region of high concentration of water molecules
to a region of low concentration of water molecules through a partially permeable membrane.

The water molecules move through aquaporins.

Osmosis is a special type of diffusion

Osmosis is a special case of diffusion in which only movement of water molecules are involving the
movement of water.
Water potential
This is a measure of the tendency of water molecules to move from one place to another. Water
potential can also be described as a measure of how freely water molecules can move in a particular
environment.

Osmosis in animal and plant cells

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If the water potential surrounding an animal cell is higher than that of the cell, it will gain water, swell
and burst. If the surrounding solution's water potential is lower than that of the cell, it will lose water
and shrivel up had crenate. This is why it is so important to maintain constant water potential inside
the bodies of animals.

NOTE:

 Osmosis can be described as the net diffusion of water molecules from an area of higher
water potential to an area of lower water potential, through a partially permeable membrane.
 In the case of osmosis, ‘water potential’ is used to describe the relative concentration of
water molecules.

A high water potential means there is a low concentration of solute, in other words a high
concentration of water. Pure water has the highest water potential possible.

When comparing 2 solution’s water potentials, they can be described as:

 Isotonic solution - the two solutions have the same water potential. i.e two solutions have
equal solute concentration.
 Hypertonic solution - the solution with a lower water concentration relative to another solution.
It has high solute concentration, so has lower concentration of water, therefore a lower water
potential.
 Hypotonic solution - the solution with a high water concentration relative to another solution. It
has low solute concentration, so has high concentration of water, therefore a high water
potential.

2. DIFFUSION

Diffusion is the passive movement of molecules down a concentration gradient, from an area of high
concentration to an area of lower concentration through a partially permeable membrane.
There are two types of diffusion –

(i) Simple diffusion,

(ii) Facilitated diffusion and osmosis.

Simple diffusion

 Simple diffusion is the passive movement of small, non-polar / uncharged lipid soluble
molecules, such as carbon dioxide and oxygen, from an area of high concentration to an
area of low concentration.
 The molecules move directly through the phospholipid bilayer.

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Facilitated diffusion

 Facilitated diffusion is the movement of large polar / charged molecules down the
concentration gradient involving membrane proteins.
 These molecules cannot pass across the phospholipid bilayer
 It requires a membrane protein to transport large, polar (charged) and water soluble
molecules across the membrane, since these molecules cannot pass through the non-polar
fatty acid tails inside of the bilayer.
 Charged particles or large molecules move across the membrane through protein-lined
pores.

ACTIVE TRANSPORT

 This is the movement of all types of molecules through carrier proteins from an area of low
concentration to an area of high concentration.
 This process moves particles against the concentration gradient, and so requires energy in
the form of ATP.

ENDOCYTOSIS
This is transport of large particles into the cell. The particles are enclosed in vesicles made from the
cell surface membrane and transported into the cell / organelle.

EXOCYTOSIS.
This is transport of large particles out of the cell. The vesicles made within the cell fuses with the cell
surface membrane and transported out of the cell.
In exocytosis, vesicles containing large particles or substances are fused with the membrane and
leave the cell/organelle.

MEMBRANE PROTEINS INVOLVED IN TRANSPORT ACROSS THE CELL MEMBRANE

Different types of protein in a membrane are involved in different types of transport:
● Carrier proteins - can move particles through the membrane by both active transport and facilitated
diffusion.
● Channel proteins - forms pores in the membrane for polar particles to move through by facilitated
diffusion.
● Extrinsic proteins - a membrane protein that goes through only 1 layer of the bilayer.
● Intrinsic proteins - a membrane protein that goes through both layers of the bilayer.

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PROTEINS

 The basic unit is an amino acid.

 Amino acids are the monomers from which proteins are made.

Generally, amino acids have the following structural properties:

 A carbon (the alpha carbon) bonded to the four groups below:
 A hydrogen atom (H)
 A Carboxyl group (-COOH)
 An Amino group (-NH2)
 A "variable" group or "R" group

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  R groups vary between amino acids and affects the way amino acids bond with each other in
a polypeptide chain.
 Different proteins can appear very different and perform diverse functions (e.g. the water-
soluble antibodies involved in the immune system and the water-insoluble keratin of hair,
hooves and feathers). Despite this, each one is made up of amino acid subunits.
 There about 20 different amino acids that all have a similar chemical structure but behave in
very different ways because they have different side groups (R groups).
 Hence, arranging them together in different combinations produces very different proteins.

e.g

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  When 2 amino acids are joined together (condensation) the amino group from one and the
acid group from another form a bond, producing one molecule of water. The bond formed is
called a peptide bond.


 Hydrolysis is the opposite of condensation and is the breaking of a peptide bond using a
water molecule.

There are 20 different amino acids with different R groups. Amino acids are joined by peptide bonds
formed in condensation reactions. A dipeptide contains two amino acids and polypeptides contain
three or more amino acids.

The structure of proteins is determined by the order and number of amino acids, the bonding present
and the shape of the protein:

FOUR PROTEIN STRUCTURE TYPES

The four levels of protein structure are distinguished from one another by the degree of complexity in
the polypeptide chain. A single protein molecule may contain one or more of the protein structure
types: primary, secondary, tertiary, and quaternary structure.

1. Primary Structure
Primary Structure describes the unique order in which amino acids are linked together to form a
protein. Proteins are constructed from a set of 20 amino acids.
● The primary structure of a protein is the sequence and number of amino acids in a protein.

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All amino acids have the alpha carbon bonded to a hydrogen atom, carboxyl group, and an amino
group. The "R" group varies among amino acids and determines the differences between these
protein monomers. The amino acid sequence of a protein is determined by the information found in
the cellular genetic code. The order of amino acids in a polypeptide chain is unique and specific to a
particular protein. Altering a single amino acid causes a gene mutation, which most often results in a
non-functioning protein.

2. Secondary Structure
Secondary Structure refers to the coiling or folding of a polypeptide chain that gives the protein its 3-
D shape. ‘
● The secondary structure is the shape that the chain of amino acids folds into – either alpha helix or
beta pleated sheet. The shape is determined by the hydrogen bonding
There are two types of secondary structures observed in proteins. One type is the alpha (α)
helix structure. This structure resembles a coiled spring and is secured by hydrogen bonding in the
polypeptide chain. The second type of secondary structure in proteins is the beta (β) pleated sheet.
This structure appears to be folded or pleated and is held together by hydrogen bonding between
polypeptide units of the folded chain that lie adjacent to one another.

3. Tertiary Structure
Tertiary Structure refers to the comprehensive 3-D structure of the polypeptide chain of a protein.
There are several types of bonds and forces that hold a protein in its tertiary structure. 
 Hydrophobic interactions greatly contribute to the folding and shaping of a protein. The "R"
group of the amino acid is either hydrophobic or hydrophilic. The amino acids with hydrophilic
"R" groups will seek contact with their aqueous environment, while amino acids with
hydrophobic "R" groups will seek to avoid water and position themselves towards the center
of the protein. 
 Hydrogen bonding in the polypeptide chain and between amino acid "R" groups helps to
stabilize protein structure by holding the protein in the shape established by the hydrophobic
interactions.
 Due to protein folding, ionic bonding can occur between the positively and negatively
charged "R" groups that come in close contact with one another.
 Folding can also result in covalent bonding between the "R" groups of cysteine amino acids.
This type of bonding forms what is called a disulfide bridge..

4. Quaternary Structure
Quaternary Structure refers to the structure of a protein macromolecule formed by interactions
between multiple polypeptide chains. Each polypeptide chain is referred to as a subunit. Proteins with
quaternary structure may consist of more than one of the same type of protein subunit. They may also
be composed of different subunits. It contains four subunits: two alpha subunits and two beta
subunits.

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How to Determine Protein Structure Type

 The three-dimensional shape of a protein is determined by its primary structure. The order of
amino acids establishes a protein's structure and specific function.
 The distinct instructions for the order of amino acids are designated by the genes in a cell.
 When a cell perceives a need for protein synthesis, the DNA  unwinds and is transcribed into
an RNA copy of the genetic code.
 This process is called DNA transcription. The RNA copy is then translated to produce a
protein. The genetic information in the DNA determines the specific sequence of amino acids
and the specific protein that is produced. Proteins are examples of one type of biological
polymer. Along with proteins, carbohydrates, lipids and nucleic acids  constitute the four major
classes of organic compounds in living cells.

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Fibrous proteins are made of long molecules arranged to form fibres (e.g. in keratin). Several helices
may be wound around each other to form very strong fibres.
Fibrous, globular proteins and conjugated Proteins
1. Fibrous proteins
- They are long (fibrous)
- Are tough hence have structural role
- Insoluble in water
- Found in tendons, bones, muscles, hair, nails, horns, skin, beaks, hooves etc.

Globular proteins are made of chains folded into a compact structure. One of the most important
classes are the enzymes. Although these folds are less regular than in a helix, they are highly specific

85
and a particular protein will always be folded in the same way. If the structure is disrupted, the protein
ceases to function properly and is said to be denatured.
- They are spherical /compact
- Soluble in water
- Are involved in metabolism e.g. enzymes are involved in catalysis
- Example
1. Enzymes such as amylase
2. Antibodies
3. Some hormones such as glucagon and insulin

Conjugated proteins
- Consist of amino acids and other non-protein chemical groups (prosthetic groups)
- Examples of conjugated proteins are
1. Haemoglobin – prosthetic group is haem group that contains iron. Oxygen binds to iron
2. Glycoprotein – prosthetic group is carbohydrate
3. Lipoprotein – prosthetic group is lipid
Note; If a protein is made up of several polypeptide chains, the way they are arranged is called the
quaternary structure. Again, each protein formed has a precise and specific shape (e.g. haemoglobin)

FUNCTIONS OF PROTEINS
1. All enzymes are proteins.
2. Structural: e.g. collagen and elastin in connective tissue, keratin in skin, hair and nails.
3. Contractile proteins: actin and myosin in muscles allow contraction and therefore movement.
4. Hormones: many hormones have a protein structure (e.g. insulin, glucagon, growth hormone).
5. Transport: for example, haemoglobin facilitates the transport of oxygen around the body, a type of
albumin in the blood transports fatty acids.
6. Transport into and out of cells: carrier and channel proteins in the cell membrane regulate
movement across it.
7. Defence: immunoglobulins (antibodies) protect the body against foreign invaders; fibrinogen in the
blood is vital for the clotting process.

ENZYMES
 These are globular proteins that act as biological catalysts to speed up chemical reactions
by reducing the activation energy.
 Activation energy is the energy required to start a reaction.
 A catalyst is a substance that speeds up a reaction by lowering the activation energy.
 Enzymes, being biological catalysts, are specific in action, that is, they catalyze a specific
reaction or groups of reactions. So, enzymes show a great specificity

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  The majority of the reactions that occur in living organisms are enzyme-controlled.
 Enzymes are proteins and thus have a specific shape. They are therefore specific in the
reactions that they catalyse - one enzyme will react with molecules of one substrate.
 The site of the reaction occurs in an area on the surface of the protein called the active site.

Enzyme Controlled Reactions

- Reactions proceed because the products have less energy than the substrates.
- However, most substrates require an input of energy to get the reaction going, (the reaction is
not spontaneous).
- The energy required to initiate the reaction is called the activation energy.
- When the substrate(s) react, they need to form a complex called the transition state before
the reaction actually occurs. This transition state has a higher energy level than either the
substrates or the product.
- Enzymes lower activation energy.
Graph indicating activation energy with and without enzyme.

a b
Energy

Reaction Time
a. Energy in reactants
b. Activation energy with enzyme
c. Activation energy without enzyme
d. Energy in products

Factors Affecting the Rate of Reaction

1. Temperature
2. pH
3. Enzyme Concentration
4. Substrate Concentration Cofactors

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Most enzymes require additional help from cofactors, of which there are 2 main types:
1. Coenzymes - these are organic compounds, often containing a vitamin molecule as
part of their structure.
2. Metal ions - most speed up the formation of the enzyme-substrate complex by
altering the charge in the active site e.g. amylase requires chloride ions, catalase
requires iron.

Inhibitors
Inhibitors slow down the rate of a reaction. Sometimes this is a necessary way of making sure that the
reaction does not proceed too fast, at other times, it is undesirable.

 Reversible Inhibitors:
 Competitive reversible inhibitors
 Non-competitive reversible inhibitors
 Irreversible Inhibitors: These molecules bind permanently with the enzyme molecule and so
effectively reduce the enzyme concentration, thus limiting the rate of reaction, for example,
cyanide irreversibly inhibits the enzyme cytochrome oxidase found in the electron transport
chain used in respiration. If this cannot be used, death will occur.

The primary structure of an enzyme determines its 3D (tertiary) structure and its properties.

 Primary structure is the sequence of amino acids joined by peptide bonds to form a
polypeptide chain.
 These amino acids have R-groups.
 These R-groups determine the type of chemical bonds such as hydrogen
 The chemical bonds determine the shape and property of the active site of enzymes. These
active sites allow specific substrates to bind to form enzyme- substrate complex.
 Polar or hydrophilic R-groups face outwards in the enzyme while non-polar or hydrophobic R-
groups face inwards of the enzyme and this ensures solubility of enzymes.

DNA AND THE GENETIC CODE

EVIDENCE FOR THE STRUCTURE OF DNA

 The Structure of DNA

 DNA is a polymer of nucleotides.
 Nucleotides are made up of:
- a phosphate.
- a sugar - deoxyribose.
- a base - either adenine, guanine, thymine or cytosine.

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 DNA is a macromolecule polymer made of subunits called nucleotides. The nucleotides are
arranged in two chains which are coiled into a spiral shape called a double helix.
 There are four types of nitrogenous bases in DNA
- Adenine
- Thymine
- Cytosine
- Guanine
 Adenine and Guanine are called purines while Thymine and Cytosine are called pyrimidines.

 There is a fixed rule of pairing nitrogenous bases, mainly based on their mass i.e. bases with
equal mass pair up together.
 A purine pairs up with a pyrimidine as shown below;

GC  Triple hydrogen bond

A=T = Double hydrogen bond

 Adenine pairs with thymine by formation of two hydrogen bonds while Guanine pairs with
cytosine by formation of three hydrogen bonds

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 G and C have triple hydrogen bonds because there are two O-H and one N-H between them.
T and A have double hydrogen bonds because there is one O-H and one N-H between them
NB:
 The two strands are antiparallel.
 DNA is directional in both strands, signified by a 5' and 3' end. This notation signifies which
side group is attached the DNA backbone. The 5' end has a phosphate (P) group attached,
while the 3' end has a hydroxyl (OH) group attached.

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THE STRUCTURE OF RNA

 It is a single stranded molecule.

 The pyrimidine Thymine never occurs but is always replaced by Uracil, another pyrimidine.
 It is much shorter than DNA.
 It comes in three different forms, ribosomal, transfer and messenger.
 The mononucleotides of RNA contain a pentose sugar called ribose.

 The nitrogenous bases in RNA are:

A – Adenine

U – Uracil

G – Guanine

C – Cytosine

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They pair up as follows;

A=U - Two hydrogen bonds

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GC - Three hydrogen bonds

 There are 3 types of RNA in the cells:

(i) messenger RNA (mRNA)

(ii) transfer RNA (tRNA)

(iii) Ribosomal RNA (tRNA)

1. Messenger RNA (mRNA)

 It is synthesized by the antisense DNA strand (template strand) in the nucleus through
complementary base pairs.
 Its role is to carry genetic information from the antisense DNA strand in the form of codons
(triplet of bases) to the surface of ribosomes in the cytoplasm.
 The mRNA molecules are linear (straight chains) to ensure that the codons are exposed for
reading and translation of the codons into a sequence of amino acids.
 During transcription (synthesis of the mRNA by the antisense DNA (5’-3’) strand through
complementary base pairing in the nucleus), enzymes known as DNA helicase and RNA
polymerase are used.

2. Transfer RNA (tRNA)

 It is synthesized by the DNA through transcription in the nucleus and then passes out to the
cytoplasm.
 The tRNA molecule is clover leaf shaped. When stretched out, it has 80 bases and it runs
from 5’ to 3’ end.
 At the 3’ end there is a free OH group which acts as a binding site for the amino acids.
 The tRNA molecule also has anti –codon loop which consist of an anti-codon.
 An anti-codon is a triplet of bases on tRNA which is complementary to the codon on mRNA.
 Its function is to carry a specific amino acid from the cytoplasm to the ribosome and to
attach to the mRNA so that the amino acids are aligned correctly to form polypeptide.

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 Differences between mRNA and tRNA

The mRNA The tRNA

1. Straight chain Clover leaf shaped (folded)

2. It is of variable length Fixed length

3. Usually a longer chain Usually a shorter chain

4. No hydrogen bonds Has hydrogen bonds

3. Ribosomal RNA (rRNA)

 It is synthesized in the nucleolus in the nucleus

 Its function is to synthesize ribosomes by forming a component of the ribosomes.
 It is highly folded into a compact globular shape

DNA REPLICATION

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Since DNA forms the genetic code and that it is known that genes may be inherited, it follows that
DNA must be copied exactly before being incorporated into gametes at meiosis.

It also follows that all new cells in an organism must gain a copy of the genes at mitosis, because they
are able to continue the characteristic biochemical behaviour of that organism.

Before a cell duplicates and is divided into new daughter cells through either mitosis   or meiosis,
DNA, must be replicated in order to ensure that each new cell receives the correct number of
chromosomes.

DNA replication is semi conservative – meaning when replication occurs an original strand pairs with
a newly synthesised strand to form a double helix.

SEMI CONSERVATIVE REPLICATION OF DNA

 DNA helicase breaks the hydrogen bonds between base pairs to separate the two strands of
DNA and expose bases.
 The two DNA strands act as templates to synthesize new DNA molecules.
 A short piece of RNA called a primer binds to the 3' end of the strand.
 Mononucleotides bind to complementary mononucleotides of the DNA template strands
 DNA polymerase catalyses the addition of mononucleotides according to base pairs pairing
rule where A pairs with T and C pairs with G.
 Once both the continuous and discontinuous strands are formed all RNA primers are
removed.
 DNA ligase catalyze the synthesis of phosphodiester bonds between these mononucleotides
from 5’ to 3’ and 3’ to 5’, respectively, forming a leading strand and a lagging stand,
respectively.
 Each new DNA molecule has one old parental DNA strand and one new DNA strand hence
semi conservative replication of DNA.
 The DNA template strand is the strand being copied to synthesise a new strand
 The template strand is also called the antisense strand.

NB

 DNA polymerase cannot catalyze the formation of phosphodiester bonds in the 3’ to 5’

direction and therefore the 3’ to 5’ end is replicated in short sections, known as Okazaki
fragments. This is a lagging strand because its synthesis is slow.
 These fragments or sections are joined by the enzyme DNA ligase to form a continuous
polynucleotide chain.

Meselson and Stahl Experiment to show that DNA Replicates Semi –Conservatively.

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They grew E.coli bacteria in a medium containing heavy nitrogen (15N) for many generations so that
all the E.coli cells contained only the heavy DNA. Nitrogen forms the nitrogenous bases in the DNA.

 They took a known mass of a sample of these bacteria, isolated DNA through centrifuging
and put it in a separating solution containing caesium chloride.
 The DNA band occupied the lower position of the tube indicating that all the strands of these
DNA had heavy nitrogen.
 They grew the remaining bacteria in a medium containing light nitrogen ( 14N) for several
generations.

(i) In the 1st generation (1st replication)

 They grew the remaining bacteria in a medium containing light nitrogen ( 14N) for one
generation.
 After this first generation, they took the same known mass of a sample of these bacteria,
isolated DNA through centrifuging and put it in a separating solution containing caesium
chloride.
 The DNA band occupied the middle position indicating that all the strands of DNA had
heavy and light strands forming hybrid DNA, hence proving semi conservative replication
of DNA.

(ii) In the 2nd generation

 They grew the remaining bacteria in a medium containing light nitrogen ( 14N) to get 2nd
generation
 After this 2nd generation, they took the same known mass of a sample of these bacteria,
isolated DNA through centrifuging and put it in a separating solution containing caesium
chloride.
 The DNA had two bands in the separating solution with equal thickness i.e. a hybrid band of
DNA in the middle position and a light band of DNA near the top.

(iii) In the 3rd generation

 They grew the remaining bacteria in a medium containing light nitrogen ( 14N) to get 3nd
generation
 After this 3nd generation, they took the same known mass of a sample of these bacteria,
isolated DNA through centrifuging and put it in a separating solution containing caesium
chloride.
 The DNA had two bands in the separating solution i.e. a hybrid band of DNA in the middle
position whose thickness was one third and a light band of DNA near the top whose thickness
was two thirds. The ratio of the light to hybrid band was 3:1

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97
98
Meselson and Stahl’s experiment supported the theory of semi-conservative replication and
refuted the idea of conservative replication
The experiment showed that after one replication (generation) in a medium containing light nitrogen,
the DNA band occupied the middle position in the separating medium proving that all the DNA
molecules had one strand containing heavy nitrogen and the other strand containing light nitrogen
(hybrid DNA), and this explains semi conservative replication of DNA, where one original strand
containing 15N paired up with a newly synthesized strand containing 14N. If there had been
conservative replication, they would have found half the DNA molecules containing heavy nitrogen
and the other half containing light nitrogen.
However, in all replications, a parental strand (15N) will always be there, further giving evidence of
semi conservative replication of DNA

THE GENETIC CODE

The genetic code is the set of rules used by living cells to translate information encoded within genetic
material (DNA or mRNA sequences of nucleotide triplets, or codons) into proteins. Translation is
accomplished by the ribosome, which links amino acids in an order specified by messenger RNA
(mRNA), using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three
nucleotides at a time.

 The nature of the genetic code is highly similar among all organisms and can be expressed in
a simple table as shown below;

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The nature of genetic code

Property of genetic code

1. Triplet code
There are 20 different types of amino acids. There are 4 different
types of bases. So, if one type of base codes for one type of
amino acid, only 4 out of 20 different types of amino acids will be
coded for (41=4); for 2 different types of bases, only 16 different
types of amino acids will be coded for (42=16). For 3 different
types of bases, 64 triplet of bases will be obtained which are more
than enough (43=64).
The importance of triplet code is that all the 20 different types
of amino acids, the start signal and the stop signals are
coded for.

2. Non overlapping Each triplet is discrete / each base is only used once in a triplet
i.e. no base from one triplet is part of another triplet. The
importance of this is to avoid confusion about which amino acid is
being coded for

3. Degenerate Degenerate code means that one amino acid can be coded for by
more than one triplet of bases. Usually, if the first 2 bases are the
same the triplet of bases with those bases would code for the
same amino acid e.g. CCC, CCA, CCT, CCG code for the amino
acid called proline.
The importance of degeneracy is to offer protection against
substitution mutation that affects the 3rd base. It results into silent
mutation as it is never expressed in the phenotype.

PROTEIN SYNTHESIS
DNA is the molecule which controls the synthesis of proteins. Proteins are used for growth and repair
and also as enzymes, in which form they catalyse all other cellular activities.
Thus DNA is able to exert a controlling influence over the whole cell and ultimately, the whole
organism. The segments of DNA which hold the key to this control are the genes
- A gene is a sequence of bases on one strand of DNA which codes for a polypeptide (sequence
of amino acids), or it is also a small section of DNA that codes for a polypeptide chain (chain of
amino acids)
- Gene locus is the region on the chromosome where a gene is located.
Protein synthesis relies on the effective communication of the coded information held in the genes to
the sites of protein manufacture, the ribosomes in the cytoplasm.
Since DNA is part of larger structures (chromosomes), which are unable to move from the nucleus,
intermediate messenger molecules are needed. These are messenger RNA molecules.

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The three major stages/process in protein synthesis are;
(i) Transcription
(ii) Post-transcription modification of pre-mRNA
(iii) Translation

Transcription in eukaryotic cells

Definition:
This is the synthesis of mRNA by the anti-sense (template) DNA strand in the nucleus through
complementary base pairs.
During transcription;
 DNA helicase breaks down the hydrogen bonds between the base pairs to get two separate
DNA strands.
 The anti-sense DNA strand acts as a template to synthesize mRNA.
 Nucleotides bind to complementary nucleotides of the anti-sense DNA strand/template
strand.
 RNA polymerase catalyses the addition of mononucleotides according to base pairs pairing
rule where A pairs with U and C pairs with G.

 DNA ligase catalyze the synthesis of phosphodiester bonds between these

mononucleotides from 5’ to 3’ forming a continuous stand.
 The synthesized mRNA leaves the nucleus through a pore to the cytoplasm.
 The DNA strand is the strands wind again to form the double helix.

NB
The DNA strand from which the rnais synthesized is called the anti-sense DNA strand.
It is also called template strand because it provides the pattern ordering the sequence of nucleotides
in RNA transcript.

TRANSLATION
Definition
This is the conversion of the specific sequence of codons (triplet of bases on the mRNA into a specific
sequence of amino acids (polypeptide chain) on the surface of ribosomes. The mRNA acts as a
template during translation to synthesis protein. The amino acids are joined by peptide bonds.
These amino acids are carried to the surface of ribosomes by specific tRNA molecules

Amino acid activation

 When mRNA reaches the ribosome, it binds to a site on the small sub unit of the ribosome. This
sub unit binds to two codons at a time.
 This binding of mRNA to ribosome triggers amino acid activation.
 Amino acid activation is the binding of amino acids to specific tRNA molecules at the end of 3’

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 This binding requires;
1. An enzyme called amino acyl tRNA synthetase
2. Energy from ATP

Translation process
 The mRNA binds to the smaller sub-unit of the ribosome. The ribosome binds or encloses 2
codons at a time.
 This triggers amino acid activation (amino acids bind to specific tRNA at 3’ end)
 The first tRNA with its specific amino acid moves to the mRNA on the ribosome where its
anti-codon binds to complementary codon on mRNA by hydrogen bonds
 The second amino acid is added in the same way to the second codon on mRNA
 Peptide bond is formed between the 2 amino acids catalyzed by peptidyl transferase
enzyme in a condensation reaction to form a dipeptide molecule (chain initiation).
 The ribosome moves one codon further along the mRNA. The first tRNA dissociates from
the codon on the mRNA and the amino acid and moves to the cytoplasm.
 The third amino acid is added in the same way as the first two (chain elongation).
 This continues till a stop codon (UAA/UGA/UAG) is reached (chain termination)

GENE MUTATIONS
- A gene mutation is the change in a base sequence on the DNA.
- If mutations occur in reproductive cells, in ovaries and testes, then the gametes (sperm and egg
cells) formed from these reproductive cells will have mutations and can be inherited.

Substances that can cause mutations are called mutagens and include;
1. Harmful chemicals e.g. nitrous acid
2. Ionizing radiations e.g. gamma rays

Types of gene mutations

1. Frame shift gene mutations
This is when there is a change in the entire sequence of the triplet of bases from the region of point of
mutation.
Occurs as a result of insertion or deletion of nucleotides. They are more harmful as they result in
change in base sequence, hence change in amino acid sequence in the polypeptide coded for.

2. Non frame shift mutations

- Only one or few of the nucleotides in the gene/base sequence are altered.
- Occurs as a result of substitution of nucleotides and inversion.
- They are less harmful.
- However they could have serious effect if a stop codon is introduced.
- They may not have any effect on the phenotype because;

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 (i) It could be a recessive allele that does not express itself phenotypically
(ii) It could be an intron that is removed during post transcription modification.
(iii) The new codon could be a codon that codes for the same amino acid. This is because the
genetic code is degenerate i.e. several codes code for the same amino acid.

QUESTION
Explain how a gene mutation results in a protein that does not function normally
- Gene mutation is the change in a base sequence on the DNA due to insertion, deletion or
substitution.
- This gene with different bases is transcribed into mRNA with different codons
- This mRNA is translated into different amino acids in the polypeptide chain/primary structure.
- These amino acids have different R groups which determine different chemical bonds that in turn
give rise to different shape/structure of protein that cannot function properly or has different
functions.

EXAMPLES OF GENETIC DISORDES DUE TO MUTATIONS

1. CYSTIC FIBROSIS (CF)

Genetic disorder caused by a recessive allele that codes for faulty CFTR protein (chloride channel
protein) on the membrane of the epithelial cells. This causes accumulation of thicker and stickier
mucus in the mucus secreting ducts such as pancreatic duct in the pancreas, airways, oviducts, cervix
and sperm ducts.
It result from mutations that affect CFTR gene on chromosome no. 7 giving rise to faulty CFTR gene
that codes for a faulty CFTR protein.

How CFTR protein works

 CFTR protein forms gated channels that open in presence of ATP.
 The protein allows chloride ions to diffuse into or out of the cell by facilitated diffusion.
 ATP binds to the CFTR ATP binding site and the ASTP is hydrolysed releasing energy. This
causes the shape of the protein and opens the channel protein to allow chloride ions to
diffuse
 The chloride ions to diffuse out of the epithelial cells that lines mucus producing ducts, tubes
and glands.
 Movement of chloride ions causes water to move out of the cells by osmosis into the mucus,
making it thinner.

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NOTE: In the sweat ducts, the CFTR protein works by allowing movement of the chloride ions to
diffuse into the cells lining the sweat ducts.

Examples of common gene mutations that causes CF include:

 DF- 508; whereby the 508th triplet of bases (the CFTR gene consists of 1480 triplet of bases)
on the CFTR gene is deleted so that phenylalanine amino acid is not coded for in the CFTR
protein; and this faulty protein will not fold correctly, hence will not allow chloride ions to
diffuse from the epithelial cells, water will also not diffuse into the mucus.

 Another type of gene mutation affecting CFTR gene is loss of ATP binding site on the CFTR
protein.
This means that ATP will not bind, there will be no energy to open the chloride channel protein (CFTR
protein), Chloride ions will not move, causing the accumulation of chloride ions in the epithelial cells.

Question
a) Give reasons why most designed DNA tests for CF mutations give false negative
results.
Answer;
CF is caused by many different types of mutations, about 2000, and so any designed DNA tests will
detect few mutations and leave out others. So,the person maybe declared negative for CF, but it is a
false negative.
b) CF analysis is done in the body cells (diploid cells) and not in the gametes (haploid
cells). Suggest reasons for this.
Answer;
 It is easier to obtain body cells than gametes
 Body cells are genetically similar unlike gametes.
 Diploid cells have full no. of chromosomes and this allows mutations to be detected
from all the chromosomes; gametes, haploid cells, have half the no. of chromosomes.

THE EFFECTS OF FAULTY CFTR PROTEIN

1. Respiratory problems
Thick and sticky mucus accumulate in the respiratory ducts and this results to:
 Reduction in airflow due to reduced lumen size of bronchioles

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  Reduction in gaseous exchange between the alveoli and lung capillaries as diffusion
distance is increased
 Bacterial infections in lungs and the respiratory tract as the trapped mucus become a
source of infection.
 The trapped mucus makes the respiratory cells lose their antibacterial properties because
white blood cells and antibodies do not work well in dehydrated mucus.

2. Digestive problems
 Thick and sticky mucus blocks the pancreatic duct in the pancreas so that digestive enzymes
don’t reach the duodenum and this reduces digestion of food.
 Also there is reduced absorption of food molecules as thick mucus clog the villi and microvilli.
In addition, it causes fatigue due to less energy.
Enzymes trapped within the pancreas cause cysts (swellings) and this cause damage to insulin
producing cells, leading to diabetes.
3. Reproduction problems
- In women, mucus block the cervix and oviducts are blocked hence infertlity.
- In men, the vas deferens (sperm ducts) are blocked with mucus so sperm cannot leave the
epididymis

4. Saltier sweat.
In the CF patient, CFTR protein channels are non-functional, causing accumulation of Cl ions in the
sweat in the sweat duct that also attract Na ions and water, from the sweat gland so that there is more
sweat with a lot of salts. This is why salt supplement should be given to CF patients to compensate for
the lost ones.

5. Nervous system problems

- Accumulation of Cl ions in the sweat in the sweat duct that also attract Na+ ions to balance the
charges.
- Excessive loss of Na+ ions in sweat affects transmission of nerve impulses.

MECHANISMS THAT REDUCE THE EFFECT OF CF

1. Taking drugs –Antibiotics – to treat bacterial infections
- Mucolytics – that break down the thick mucus
- Asthma drugs – to relieve breathing difficulties
2. Taking enzymes -To aid in digestion
3. Taking hormone such as insulin
4. Physiotherapy – Tapping the affected part e.g the chest.
This loosens and removes the thick, sticky mucus from the lungs to improve airflow of air,
increase
gaseous exchange and reduces bacterial infection.

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5. Transplant of the affected organ
6. Infertility treatment through IVF.
7. Gene therapy - This is the transfer of a normal allele, carried by a vector, to a target cell so that it is
expressed to produce a normal functional protein.

SICKLE CELL ANAEMIA

 This is an inherited blood disorders that affect Shape of red blood cells lowering their surface area
transport oxygen.
The sickle shaped rbcs also are not able to the narrow lumen of blood capillaries hence they clog
/block the capillaries causing some cells to lack oxygen.
 Its caused by recessive allele
 symptoms of sickle cell anaemia include;
1) Shortness of breath as the body tries to take in more oxygen
2) Lack of energy due to insufficient oxygen in the blood hence fatigue
 If an individual has one defective allele, he/she is a carrier. This condition is results in mild
anaemia because both alleles are expressed.
 If both alleles are defective the condition is results severe anaemia.

Sickle cell anaemia and malaria

- Carriers for this condition have protection against malaria. The Plasmodium parasite that causes
malaria does not survive and reproduce inside sickle shaped red blood cells.
- Hence the condition contains a selective survival advantage on carriers allowing the mutation to
be passed on to successive generations.
- So in malaria prone zones the highest pupation is that of carriers.
- The carriers suffer from mild anemia as mild form of malaria.

TREATMENT OF GENETIC DISORDERS

Mainly done through gene therapy

GENE THERAPY
 This is the transfer of a normal allele by a vector to a target cell, so that it is expressed to
produce a normal functional protein.
 The requirements for gene therapy are:-
1. Restriction Enzymes/ Restriction Endonucleases - They cut DNA at restricted
sites of specific bases.
2. DNA Ligases - It catalyzes the formation of phosphodiester bonds between the
allele and the vector, forming a recombinant DNA (rDNA).
3. Vectors -These are molecules that carry normal alleles to the target cells.

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  There are 3 types of vectors:-
1. Harmless Virus
2. Plasmids
3. Liposomes
 Liposomes are vesicles that consist of a membrane made of phospholipid bilayer.
 This layer is similar to the animal phospholipid bilayer of the plasma membrane,
hence they can easily fuse.

Once the DNA is introduced into the host, it codes for the synthesis of the right protein, relieving the
symptoms of the disorder.

PRINCIPLE OF GENE THERAPY

1. Restriction enzyme is used to cut out the normal allele from the DNA.
2. The same restriction enzyme cuts open a plasmid.
3. The allele is introduced into the plasmid using enzyme ligase that catalyses the formation of
phosphodiester bonds between the allele and the plasmid, forming recombinant DNA (rDNA).
4. The rDNA molecules are inserted into a vector.
5. The vector carrying the recombinant DNA is introduced to the host with the defective allele
- The mode of introduction depends on the disorder to be treated.
e.g
- in case of sickle cell anaemia it can be introduced as an injection into the circulatory system.
- For CF, if the target cells are in the lungs, the complexes are taken as aerosol/ nasal spray
to the target cells. If the target cells are the digestive and reproductive system cells, the
complexes are
injected into the blood.
Inside the mucus producing cells, the allele is expressed (Transcription and
Translation) to form a
normal CFTR channel protein. This protein allows chloride ions to leave the cells
and move into
mucus. Water leaves the cell by osmosis and enters mucus causing the mucus to
become less sticky.

PROBLEMS WITH THE CURRENT GENE THERAPY FOR CF.

1. Only about 25% of the normal chloride transport is restored.
2. The effect is temporary, because when the epithelial cells with the normal allele die, they are
replaced by new cells with the faulty allele.
3. Use of viruses as a vector can cause side effects such as, immune reaction, headache, fever,
fatigue and raised heart rate
4. Delivery of the allele to the target cells is not very successful, only about 1 out of 1000 alleles
gets into the target epithelial cell nucleus.

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Types of gene therapy
Somatic gene therapy
- This is the introduction of a normal allele into the body cell/somatic cell using a vector.
- It only affects target body cells
- It is not passed on to the subsequent generations
- No consent is needed from future generations
Germ-line gene therapy
 This is the introduction of a normal allele into a sperm in the testis or egg in the ovary using a
vector such as a viral DNA.
 This is raises ethical issues due to the following reasons:-
a) It affects all the body cells
b) It is passed on to the subsequent generations.
c) Consent from future generations is required yet they are unable to give consent.
NOTE:
Genetic disorders can also treated by targeted mRNA therapy, where by a vector carrying the mRNA
carrying the base sequences coding for the normal allele is introduced.
The mRNA is then taken up, translated leading to the synthesis of the functional protein relieving the
symptoms.

Question (october, 2019)

The amino acid aspartate is converted into the amino acid arginine in the urea cycle. The urea cycle
involves several enzymes and takes place in the liver. The diagram shows part of the urea cycle.

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(a) Ornithine transcarbamylase (OTC) is one enzyme involved in the urea cycle. Ornithine
transcarbamylase deficiency is an inherited genetic disorder.
(i) Suggest how a person can be shown to have this disorder. (3)

Answer
- genetic screening / named screening method / looking for a mutation
- biochemical test / blood test / description of named molecule whose level would be different
- family history / pedigree analysis

(b)Targeted mRNA therapy is being developed to treat OTC deficiency in mice. Targeted mRNA
therapy involves injecting mice with phospholipid particles containing OTC mRNA. These
particles, shown in the diagram, target liver cells.

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The table shows the results of one study using these particles.

Explain how this treatment works. Use the information in the diagram of the urea cycle, the diagram of
the particle and the table of results to support your answer.
(6)
Answer
From the Diagram of urea cycle:
• ammonia levels will build up if carbamyl phosphate is not combined with ornithine because OTC
deficiency will result in carbamyl phosphate not combining with ornithine.
Diagram of particle:
The particle targets liver and this is where the urea cycle takes place
The phospholipids will fuse with the liver cells to enable the mRNA to enter the cells because the
phospholipids can move
The mRNA will be translated inside the liver cells producing functional OTC
The OTC will combine carbamyl phosphate with ornithine reducing the levels of urea
From the table of results:
• OTC mRNA treatment reduces the levels of ammonia back to nearly normal

GENETICS
- This is the study of inheritance.
- It deals with the transmission of alleles from parents to offspring.
- The terms used in genetics include:

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Chromosome
- Thread of DNA made up of two chromatids joined by a centromere.
- It consists of many genes.
- The region on the chromosome where a gene is located is called gene locus.
Gene
- Small section of DNA that codes for a polypeptide
- Usually a gene has two different forms called alleles
Allele
- This is one of the alternative forms of a gene (different forms of a gene).
- For example, the gene Tt has two different forms, T and t. T and t are alleles of the gene Tt.
Phenotype
- This is the outward expression of the organism
- It is determined by the inherited alleles or the environment or the interactions between the two.
- It is always expressed in words e.g. tall, short, green, black
Genotype
- Genetic constitution of an individual organism in terms of the alleles present in that organism.
Recessive
- This is the allele of a gene that only expresses itself in homozygous state such as tt, aa, bb and
does not express itself in presence of a dominant allele.
Dominant
- This is the allele of a gene that always expresses itself in both heterozygous and homozygous
condition
TT Tt

Tall
Homozygous
- Condition where the two alleles of a gene are identical e.g. TT, tt
Homozygote
- An organism whose two alleles of a gene for a particular characteristic are identical.
- Homozygotes show true breeding when crossed with genetically identical organisms
Heterozygous
- Condition where the two alleles of a gene are not identical e.g. Tt, Hh.
Heterozygote
- An organism whose two alleles of a gene for a particular characteristic are not identical.

Genetic carrier (Carrier)

- An individual with the recessive allele for the condition and does not express the condition
phenotypically, but can pass on the allele to the next generation/offspring.
Recessive genetic disorder

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  Condition that results from a faulty allele.
 To express this condition, the two faulty alleles must be present.
Filial generation
Generations after the parental generation.
Punnett square
- Diagram that is used to predict an outcome of a cross. It shows genotypes of offspring.
Monohybrid inheritance
- This is the inheritance of one gene that codes for one polypeptide that
determines one characteristic e.g. the gene for height.
Karyotype
- A diagrammatic profile of an individual’s chromosomes showing the number, form and size of the
chromosomes.

MONOHYBRID CROSSES
 The rules of genetic crosses are;
1. Parents’ phenotypes are written first. The dominant phenotype/trait is
written first in the cross.
2. Parents’ genotypes follow in the cross.
These are written in letters. For both dominant and recessive phenotypes/traits, only one letter is
used. The letter comes from the first letter of the dominant phenotype. The capital letter represents
the dominant phenotype while the lower case letter represents recessive phenotype. The
genotype/gene is represented by two letters.
3. Parents’ gametes follow in the cross.
4. Gametes must be encircled.
5. Offspring (F1) genotypes follow in the cross.
6. Offspring (F1) phenotypes follow in the cross
7. Offspring (F1) Phenotypic ratio follows (if necessary).
Genetic cross for plant height
- The allele for tallness is dominant
- The allele for dwarfness (shortness) is recessive
Parents’ phenotypes Tall x dwarf
Parents’ genotypes TT x tt
Parents’ Gametes (T) (T) (t) (t)
Offspring (F1) genotypes Tt Tt Tt Tt
Offspring (F1) phenotypes all are tall

Genetic crosses for seed morphology

- The allele for round is dominant
- The allele for wrinkled is recessive

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Parental phenotypes round x wrinkled
Parental Genotypes RR x rr
Parental Gametes (R) (R) (r) (r)
F1 genotypes Rr Rr Rr Rr
F1 phenotypes All are round

Human Genetics
- Setting up genetic crosses in humans raises ethical issues.
- Genetic pedigree diagrams are instead used to study the natural crosses and their
outcome.
- Genetic pedigree (family tree) is a diagram of family relationships.
- It uses:
(i) Squares represent males
(ii) Circles represent females
a) Lines: to represent genetic relationships;
(i) Horizontal lines connecting a male and female represent mating.
(ii) Vertical lines extending downwards from a couple represent their offspring.
Genetic pedigrees can be used to study the inheritance of genetic conditions such as CF and Sickle
cell anaemia

SEX LINKED GENES

- Refers to genes found on the sex chromosome (X or Y) but, they code for other characristics
besides
sex determination.
- Those that occur in the X chromosome are more common in males than in females because males
have one X
chromosome while females have two. Thus, males express the allele in their X chromosome even if
its
recessive while females do not express the recessive allele as long as the dominant allele is
present in the other X
chromosome.

GENETIC SCREENING
 This is the identification of genetic carriers by the identification of a faulty allele in the DNA of
any cells.
 Types of Genetic Screening:
1. Pre-implantation Genetic Screening/ Pre-implantation Genetic Diagnosis
(PIGD)
2. Pre-natal Genetic Screening
3. Genetic Screening of new born babies

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 4. Genetic screening of adults
PRE-IMPLANTATION GENETIC SCREENING/ PRE-IMPLANTATION GENETIC DIAGNOSIS
(PIGD)
 This is genetic screening of embryos created through IVF to see if they carry faulty alleles.
 The embryos that do not have faulty alleles are implanted into the woman.
 After cell division through IVF, when the embryo is 8 – 16 cells, a single cell is removed
without harming the embryo for DNA analysis to find out if there is a faulty/defective allele.
The embryo that does not have faulty allele is implanted into the woman.

Advantages of PIGD
1. Takes place beforeimplantation hence no risk of miscarriage or termination of pregnancy.
2. Involves IVF hence one is sure that the baby is free from the recessive allele.

Disadvantages of PIGD
1. Very expensive during procedure
2. Implantation can be unsuccessful.
3. Raises ethical issues because of destruction of the extra embyos of the embryos with the
faulty allele.
Some people consider the embryo a potential human being. So, it is unethical to destroy it.
4. Manipulation of the embryo during the process may lead to unwanted mutations.
5. Harm to the embryo during the process leading to subsequent health issues.
6. Can be misused to come up with designer babies.
7. Spare embryos can be used in stem cell research which some people consider unethical
(murder of a potential human).
8.
PRENATAL GENETIC SCREENING
 This involves genetic testing of embryos or foetuses.
Two types are:
a) Chorionic Villus Sampling (CVS)
b) Amniocentesis
Chorionic Villus Sampling (CVS)
 Placental tissue is removed within 8 – 10 weeks of pregnancy using a syringe and a suction
tube.
 Fetal cells are present in the placental tissue.
 DNA is analyzed in those fetal cells to detect defective genes.
Advantages of CVS
1. If termination of pregnancy is an option, it’s less traumatic for the mother as this method is
carried out early in the pregnancy.
2. Results are available immediately compared to amniocentesis as the sample size is larger
hence no need for culture.

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Disadvantages of CVS
1. Risk of miscarriage 2.5% to 4.8% risk of miscarriage due to procedure.
2. Risk of harm to foetus due to procedure with subsequent health problems.
3. May lead to false results. Parternal X chromosomes are inactivated in the placental cells
hence genetic defect on that chromosome cannot be detected at this early stage
Amniocentensis
 About 20cm3 of amniotic fluid is removed from the amniotic sac of the mother using a
syringe and a needle within 14 – 16 weeks of pregnancy.
 This amniotic fluid has few fetal cells.
 These cells are cultured for 2 – 3 weeks.
 DNA is analysed to detect defective genes.
Advantages of amniocentesis
1. Less risk of miscarriage compared to CVS (1% risk) regardless of the genetic make-up of the
foetus.
2. Defects in the paternal X chromosomes can be detected.
Disadvantages of amniocentesis
1. Carried out late in pregnancy so abortion is more traumatic to the mother if abortion is the
option.
2. Results aren’t available immediately until 2 – 3 weeks later causing more trauma and anxiety.
3. Has 1% risk of miscarriage due to procedure.
Ethical issues relating to the use of prenatal testing.
1) Fetus is living hence has right to life
2) Abortion is wrong as its murder
3) Who has right to decide if tests should be performed
4) Tests may reveal other abnormalities causing more problems
5) Who has the right to know results
6) Who has the right to make the decision for the fetus / fetus has decision rights but cannot give
consent especially when results are positive.
7) Results may deny future employment and insurance services to the child
8) Results may be used by employers and insurance services against parents of the affected
child.
Factors to consider when making the right decision on prenatal screening.
There are factors to be considered when deciding what is best in relation to prenatal screening.
These are:-
1. Harm to the foetus with subsequent health issues.
2. Right to life of the foetus.
3. Accuracy of results. – Amniocentensis is more accurate than CVS.
4. Risk of miscarriage whether the foetus is healthy or not.
5. The cost of bringing up a baby with the condition.

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 6. Mental, social and emotional issues surrounding the birth of a child with the condition.
7. Time of pregnancy – If the pregnancy has developed more than 10 weeks, one cannot carry
out CVS as its done earlier.

GENETIC SCREENING OF NEW BORN BABIES

 These new born babies are tested for defective alleles for genetic disorders such as CF.
 The blood sample is taken and the defective genes identified.
 This will help in the introduction of early treatment, in case they are sick, in terms of medicine
and nutrition which improves health in later years.

GENETIC SCREENING OF ADULTS TO IDENTIFY CARRIERS

One can go for screening?
a) If one member of a family is born with genetic disorder or born as a carrier, the other
members of the family need genetic screening.
b) If one partner in a couple has been detected to be a carrier then the other partner needs
genetic screening. This is because in case both are carriers, there is a quarter chance
that the child will have CF.
- So genetic screening helps the couple to understand their condition and make informed
decision.
Advantages of genetic screening of adults
(a) To make informed decision such as whether or not to have a child.
(b) To make informed decision to take the necessary precautions.
Disadvantages of genetic screening of adults
1. Insurance problems-termination of insurance cover or lack of insurance cover if one is known
to have a genetic disorder.
2. Difficulties in employment-loss of employment or lack of employment if one is known to have
a genetic disorder.
3. Difficult to get a partner to marry/ marriage breakages
4. Social stigma
5. Making of wrong decisions due to inaccurate results that shows you have the condition yet you
don’t have.
5. Lack of confidentiality of results. Such results can be passed to other people, insurers and
employers.

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Genetic counselling
 Involves the giving of advice to prospective parents concerning the risks of genetic disorders
in a future child. The counsellor;
 Explains results of tests
 Estimates chances of having affected child
 Discuss termination as an option
 Discuss possible treatments
 Discuss financial implications of bringing up affected child
 Discuss ethical issues that arise depending on the conclusion reached

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