Secti on III

Topic 1 CHEMISTRY AND

METABOLISM
OF CARBOHYDRATES
BIOCHEMISTRY

LONG ESSAYS
Q. 1. Give the steps of glycolysis and its ATP
Phosphofructokinase
energetics. Or ADP Fructose 1,6-bisphosphate
Describe the reactions of glycolysis. Mention Aldolase
its significance. 3-Phosphoglyceraldehyde Dihydroxyacetone phosphate Pi.
Phosphotriose isomerase
Or
NAD+
Define glycolysis. Enumerate the reactions
NADH + H+ Glyceraldehyde 3-phosphate
of pathway. Explain the energetics of dehydrogenase

pathway. Or 1, 3-Bisphosphoglycerate
ADP
Describe the anaerobic glycolysis in
Mg2+ Phosphoglycerate kinase
muscles and compute energetics. ATP 3-Phosphoglycerate
Phosphoglycerate mutase
Glycolysis is defined as the sequence of reactions 2-Phosphoglycerate
Mg2+ Enolase
converting glucose or glycogen to pyruvate or H2O
lactate, with the production of ATP. Phosphoenolpyruvate
Glycolysis is also known as Embden–Meyerhof ADP
Mg2+ Pyruvate kinase
pathway, which takes place in all cells of the body.
ATP
The enzymes required for this pathway are present in Pyruvate
the cytosomal fraction or extramitochondrial Fig. 3.1.1 Reactions of glycolysis pathway.
compartment of the cell.
If the process of glycolysis occurs

In the presence of oxygen, it is 2. In the lack of oxygen, it

known as aerobic glycolysis, is known as anaerobic
e.g. only in skeletal muscle glycolysis, e.g. it occurs in
most of the tissues like
liver, kidney and
erythrocytes
The sequence of reactions of glycolysis is shown in
Fig. 3.1.1:
Glycogen Glucose ATP Glucokinase Glucose 1-
phosphate Mg2+ Hexokinase ADP
Glucose 6-phosphate
Phosphohexose isomerase
Fructose 6-phosphate
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The glycolysis pathway can be divided into three distinct regeneration of NAD1, which can be reused by
phases: glyceraldehyde 3-phosphate dehydrogenase so that
Energy investment phase glycolysis proceeds even in the absence of oxygen to
Splitting phase 3. Energy generation phase. supply ATP.
ENERGY INVESTMENT PHASE Pyruvate
NADH + H+
In the presence of ATP and Mg 21 glucose is phosphorylated Lactate dehydrogenase
to glucose 6-phosphate by hexokinase or glucokinase, NAD+
Lactate
which is an irreversible reaction. Fig. 3.1.2 Energy generation phase.
In the presence of the enzyme phosphohexose isomerase The occurrence of uninterrupted glycolysis is
and Mg21 glucose 6-phosphate undergoes isomerization to very essential in skeletal muscle during
give fructose 6-phosphate. strenuous exercise where oxygen supply is very
Fructose 6-phosphate is phosphorylated to fructose 1,6- limited. Glycolysis in the erythrocytes leads to
bisphosphate by an allosteric enzyme phosphofructokinase lactate production because mitochondria, the centres for
(PFK). This is an irreversible and regulatory step in aerobic oxidation, are absent.
glycolysis. PRODUCTION OF ATP IN GLYCOLYSIS
SPLITTING PHASE The details of ATP generation in glycolysis are shown in
The fructose 1,6-bisphosphate (a hexose) is split to two Table 3.1.1. Under anaerobic conditions, two ATP are
trioses, glyceraldehyde 3-phosphate and dihydroxyacetone synthesized, while under aerobic conditions, eight or six
phosphate by the enzyme aldolase, hence the name ATPs are synthesized — depending on the shuttle pathway
glycolysis. that operates.
Since only glyceraldehyde 3-phosphate enters the glycolytic Table 3.1.1 Energy production in glycolysis pathway
pathway, the reversible interconversion of glyceraldehyde Enzymes involved and method of ATP Number of ATPs
3-phosphate and dihydroxyacetone phosphate is catalysed synthesis synthesized
by the enzyme phosphotriose isomerase. Thus, two Glyceraldehyde 3-phosphate 6
molecules of glyceraldehyde 3-phosphate are obtained from dehydrogenase [2 NADH, electron
one molecule of glucose. transport chain (ETC), oxidative
ENERGY GENERATION PHASE (FIG. 3.1.2) phosphorylation]
Glyceraldehyde 3-phosphate dehydrogenase oxidizes Phosphoglycerate kinase (substrate-level 2
phosphorylation)
glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate in
the presence of NAD1 and inorganic phosphate (Pi). Pyruvate kinase (substrate-level 2
phosphorylation)
The enzyme phosphoglycerate kinase acts on 1,3-
bisphosphoglycerate, resulting in the formation of 3- In the reactions catalysed by hexokinase 22
and phosphofructokinase, two ATPs are
phosphoglycerate and synthesis of ATP. This step is a good consumed
example of substrate-level phosphorylation because ATP is
Net ATP synthesis in glycolysis in aerobic 8
synthesized from the substrate without the involvement of condition
electron transport chain.
Q. 2. Outline the aerobic glycolytic pathway.
Phosphoglycerate mutase converts 3-phosphoglycerate to 2-
Define substrate-level phosphorylation. Give two
phosphoglycerate.
examples.
The enzyme enolase generates the high-energy compound
phosphoenol pyruvate from 2-phosphoglycerate. This
For aerobic glycolytic pathway, refer to the answer of Long
enzyme requires Mg21 or Mn21 and is inhibited by fluoride.
Essays Q. 1.
An allosteric enzyme pyruvate kinase catalyses the transfer
SUBSTRATE-LEVEL PHOSPHORYLATION
of high-energy phosphate from phosphoenol pyruvate to
Synthesis of ATP from substrate without the involvement
ADP, resulting in the formation of ATP. This step also is an
of electron transport chain is known as substrate-level
example of substrate-level phosphorylation and the reaction
phosphorylation. The examples are as follows:
is irreversible.
The enzyme phosphoglycerate kinase acts
The metabolic fate of pyruvate produced in glycolysis
on
depends on aerobic or anaerobic conditions in the cells.
1,3-bisphosphoglycerate, resulting in the synthesis of ATP
Under anaerobic conditions pyruvate is reduced by NADH
and formation of 3-phosphoglycerate. This step in the
to lactate in presence of the enzyme lactate dehydrogenase.
glycolytic pathway is a good example of substratelevel
The NADH utilized in this step is obtained from the
phosphorylation.
reaction catalysed by glyceraldehyde 3-phosphate
The enzyme pyruvate kinase catalyses the transfer of high-
dehydrogenase. The formation of lactate allows the
energy phosphate from phosphoenolpyruvate to ADP,
 Biochemistry 263

resulting in the formation of ATP. This step is also a

substrate-level phosphorylation.
Q. 3. Describe the citric acid cycle and its
energetics.

The most important metabolic pathway for the energy

supply to the body is the citric acid cycle (Krebs cycle or
tricarboxylic acid — TCA cycle).
This cycle not only supplies energy but also provides many
intermediates required for the synthesis of amino acids,
glucose, heme, etc.
About 65–70% of the ATP is synthesized in Krebs cycle.
The citric acid cycle is the final common oxidative pathway
for carbohydrates, fats and amino acids. 4. and 5. Formation of a-ketoglutarate
Krebs cycle is the most important central pathway The conversion or oxidative decarboxylation of isocitrate to
connecting almost all the individual metabolic pathways oxalosuccinate and then to a-ketoglutarate is catalysed by
either directly or indirectly. the enzyme isocitrate dehydrogenase (ICD).
CITRIC ACID CYCLE The formation of NADH and the liberation of CO 2 occur at
It involves the oxidation of acetyl CoA to CO2 and H2O. this stage.
It utilizes about two-thirds of total oxygen consumed by the 6. Conversion of a-ketoglutarate to succinyl CoA
body. This occurs through oxidative decarboxylation and
The name TCA cycle is used because at the outset of the catalysed by a-ketoglutarate dehydrogenase complex.
cycle, tricarboxylic acids (citrate, cis-aconitate and This enzyme is dependent on five cofactors — TPP,
isocitrate) participate. lipoamide, NAD1, FAD and CoA.
The enzymes of TCA cycle are located in mitochondrial 7. Formation of succinate
matrix in close proximity to the electron transport chain. The enzyme succinate thiokinase converts succinyl CoA to
REACTIONS OF CITRIC ACID CYCLE succinate.
Oxidative decarboxylation of pyruvate to acetyl CoA by
pyruvate dehydrogenase complex is a step, which is a This reaction is coupled with the phosphorylation of GDP
connecting link between glycolysis and TCA cycle. to GTP. This is a substrate-level phosphorylation. GTP is
The events of TCA cycle are shown in Fig. 3.1.3. converted to ATP by the enzyme phosphokinase.
1. Formation of citrate
Krebs cycle or the citric acid cycle starts with the
condensation of acetyl CoA and oxaloacetate catalysed by
the enzyme citrate synthase.
2. and 3. Citrate isomerization to isocitrate 8. Conversion of succinate to fumarate
Citrate is isomerized to isocitrate by the enzyme aconitase.
It occurs in a two-stage reaction of dehydration followed by Succinate dehydrogenase oxidizes succinate to fumarate.
hydration through the formation of an intermediate — cis-
aconitate.
FADH2 is produced during this reaction.

9. Formation of malate
The conversion of fumarate to malate with the addition of
H2O is catalysed by the enzyme fumarase.

10. Conversion of malate to oxaloacetate

Malate is oxidized to oxaloacetate by malate

dehydrogenase.

At this stage the third and final synthesis of NADH occurs.

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The oxaloacetate is regenerated, which can combine with

another molecule of acetyl CoA and continue the cycle.
The events of Krebs cycle may be summarized as follows:
Acetyl CoA 1 3 NAD1 1 FAD 1 GDP 1 Pi 1 2H2O n
2CO2 1 3NADH 1 3H1 1 FADH2 1 GTP 1 CoA
ENERGETICS OF CITRIC ACID CYCLE (FIG. 3.1.4)
During the process of oxidation of acetyl CoA through
citric acid cycle, four reducing equivalents are produced
(three as NADH and one as FADH2).
Oxidation of one NADH by electron transport chain
coupled with oxidative phosphorylation results in the
synthesis of three ATP, whereas FADH 2 leads to the
formation of two ATPs.
 Biochemistry 263

C−COO
NADH + H+ CH −COO CH −COO
Citrate
α-Ketoglutarate
dehydrogenase CH2−COO
Fig. 3.1.3 The citric acid cycle or TCA cycle.

−−
Dietary carbohydrates
(starch, sucrose, glucose)
Digestion and absorption Hormonal
Glycolysis and TCA cycle
Glycogenolysis regulation Glucose →
CO2, H2O in muscles Glucose in liver
Glycogenesis in
liver and kidney
Lactate
Blood glucose Synthesis of other
Gluconeogenesis Fasting 70 100 mg/dL
monosaccharides and
Postprandial 120−140 mg/dL amino sugars
Amino acids,
glycerol, propionate HMP shunt for
pentoses
and NADPH Glycogenolysis Excreted into

in liver urine when Synthesis of

Sources of blood blood glucose >180 mg/dL fat
glucose Utilization of
blood glucose
Fig. 3.1.4 An overview of blood glucose homeostasis.
There is one substrate-level phosphorylation.
A total of 12 ATPs are produced from one acetyl CoA, as
shown in Table 3.1.2.
262 Quick Review Series: BDS 1st Year

Energy reaction ATPs synthesized

3NADH n 3NAD1 9
FADH2 n FAD 2
cogenolysis, gluconeogenesis, etc. and the amount Hyperglycaemic effect Hyperglycaemic effect
Table 3.1.2 Energy production from Citric acid cycle that is utilizedSubstrate phosphorylation
for different (GTP)
metabolic purposes 1
like
Insulin
Total ATPs for one acetyl CoA
glycolysis, glycogenesis, fat synthesis, etc. as illustrated in Fig. 3.1.4. 12
Glucose uptake ↑
4. In the homeostasis of blood glucose, kidney plays a specialGlycolysis
role: ↑
a. Glucose is continuously filtered by the glomeruli, reabsorbed and returned
Glycogenesis to shunt
↑ HMP the blood.
↑
Lipidb. Glucose↑ is excreted in urine. If the level of glucose in
synthesis
Glucagon
Q. 4. Describe the regulation of blood glucose and blood is above
Gluconeogenesis 160–180 mg/dL,
↓ Glycogenolysis ↓ it is known as glycosuria.
Gluconeogenesis ↑
write a note on disorders of blood glucose regulation. This value (160–180 mg/dL) Glycogenolysis is known as renal threshold
↑ Epinephrine
for glucose. Glycogenolysis ↑
REGULATION OF BLOOD GLUCOSE LEVELThe maximum ability of theThyroxine renal tubules to reabsorb
(HOMEOSTASIS OF BLOOD GLUCOSE) glucose per minute is known Gluconeogenesis
as tubular maximum↑ Glucocorticoids
for
Gluconeogenesis ↑
The blood glucose concentration in a healthy individual is glucose (TmG). The value for TmG is 350 mg per minute.
Glucose utilization ↑
maintained within a narrow range. ROLE OF HORMONES IN BLOOD GLUCOSE
(extrahepatic)
The fasting blood glucose level in a postabsorptive state is 70– HOMEOSTASIS (FIG. 3.1.5) Growth hormone and ACTH
100 mg/dL (plasma glucose 80–120 mg/dL). Following the In the regulation of blood glucose concentration,
Glucose uptake ↓ hormones
ingestion of a carbohydrate meal, blood glucose may rise to play a significant role. Glucose utilization ↓
120–140 mg/dL.

Blood glucose (mg/dL)

40 50 60 70 80 90 100 110 120 130

140 150 160 170 180 190 200
Renal threshold Fasting Postprandial
To urine (<100 mg/dL) (<130 mg/dL)
Fig. 3.1.5 Hormonal regulation of blood glucose.

3. The concentration of blood glucose is dependent on the

 Biochemistry 263

quantity of glucose that enters the circulation from various

sources like dietary carbohydrates, gly-
262 Quick Review Series: BDS 1st Year

1. Insulin Diabetes mellitus is a clinical condition characterized by

It is basically a hypoglycemic hormone that lowers in blood increased blood glucose level, i.e. hyperglycaemia due to
glucose level through various me It is an insufficient or inefficient (incompetent) insulin.
antidiabetogenic hormone. Based on the requirement of insulin for treatment, diabetes
Primarily, insulin lowers blood glucose level mellitus is broadly divided into two groups:
(hypoglycemic) while the rest of the hormones oppose the 1. Insulin-dependent diabetes mellitus (IDDM) 2. Non-
actions of insulin and increase the blood glucose level insulin-dependent diabetes mellitus (NIDDM).
causing hyperglycaemia. Insulin-dependent diabetes mellitus
2. Glucagon IDDM, also known as type I diabetes or juvenile-onset
Blood glucose concentration is elevated by glucagon. diabetes. IDDM accounts for about 10–20% of the known
It enhances gluconeogenesis and glycogenolysis. diabetics.
Glucagon increases liver glucose 6-phosphatase and It occurs mainly in childhood, particularly between 12 and
phosphorylase activities and produces more glucose. 15 years of age.
3. Epinephrine This disease is characterized by almost total deficiency of
This hormone is secreted by adrenal medulla. insulin because of the destruction of beta cells of pancreas
By acting on both muscle and liver it brings about either due to drugs, viruses or autoimmunity. The patients
glycogenolysis. of IDDM require insulin therapy.
The net outcome is that epinephrine increases blood glucose Non-insulin-dependent diabetes mellitus
level. NIDDM, also called type II diabetes or adult-onset diabetes,
4. Thyroxin occurs in adults usually above 35 years.
It is a thyroid hormone. It is the most common, 80–90%, among the diabetic
By stimulating hepatic glycogenolysis and gluconeogenesis, population.
it elevates blood glucose level. It is less severe than IDDM.
5. Glucocorticoids The causative factors of NIDDM include genetic and
These hormones stimulate protein metabolism and increase environmental.
gluconeogenesis. Q. 5. Explain the glycogen synthesis in liver and
The glucose utilization by extrahepatic tissues is inhibited its hormonal regulation.
by glucocorticoids.
The overall effect of glucocorticoids is to elevate blood Glycogen is the storage form of glucose in animals. It is
glucose concentration. stored mostly in liver (6–8%) and muscle (1–2%).
6. Growth hormone and adrenocorticotropic hormone Due to more muscle mass, the quantity of glycogen in
(ACTH) muscle (250 g) is about three times higher than that in the
The anterior pituitary gland secretes growth hormone and liver (75 g).
ACTH. GLYCOGENESIS
The uptake of glucose by certain tissues like muscle, The synthesis of glycogen from glucose is glycogenesis.
adipose tissue, etc. is decreased by growth hormone. ACTH Glycogenesis takes place in the cytosol, and requires ATP
decreases glucose utilization. and UTP besides glucose (Fig. 3.1.6).
The net effect of both these hormones is hyperglycaemic. The steps involved in glycogen synthesis are as follows:
DISORDERS OF BLOOD GLUCOSE REGULATION Glucose
ATP
Hyperglycaemia Glucokinase
The term hyperglycaemia refers to an increase in the blood ADP
glucose above the normal level. Excretion of glucose in Glucose 6-phosphate
Phosphoglucomutase
urine is known as glycosuria. Glucose 1-phosphate
Hypoglycemia UTP
When the blood glucose concentration falls below 45 UDP-glucose
mg/dL, the symptoms of hypoglycemia develop. PPi pyrophosphorylase
UDP-glucose −ΟΗ
The symptoms include headache, anxiety, confusion, Glycogen initiator
sweating, slurred speech, seizures and coma, and, if not synthase
Glycogenin
corrected, death. UDP
All these symptoms are directly and indirectly related to the Glycogen primer
deprivation of glucose supply to the CNS, particularly the 13 UDP-Glucose
Glycogen synthase
brain.
13 UDP
Diabetes mellitus Elongation by glycogen synthase
 Biochemistry 263

(forming α 1, 4-bonds ) and 3. Glycogen synthesis by glycogen synthase

Branching by glucosyl 4-6 transferase
(α 1, 6-bonds )
Glycogen
Fig. 3.1.6 Glycogen synthesis from glucose (glycogenesis).
1. Synthesis of UDP-glucose
The enzymes hexokinase in muscle and glucokinase in liver
convert glucose to glucose 6-phosphate.
Phosphoglucomutase catalyses the conversion of glucose 6-
phosphate to glucose1-phosphate.
Uridine diphosphate glucose (UDPG) is synthesized from
glucose 1-phosphate and UTP by UDP-glucose
pyrophosphorylase.
Pyrophosphate (PPi) produced in this reaction is hydrolysed
to inorganic phosphate (Pi) by pyrophosphatase. This will
ensure the optimal synthesis of UDPG.
2. Importance of primer to initiate glycogenesis
A small fragment of pre-existing glycogen acts as a primer
to initiate glycogen synthesis. In the absence of glycogen
primer, a specific protein — namely glycogenin — can
accept glucose from UDPG.
Q. 1. Oral glucose tolerance test.
Glycogen synthase is responsible for the formation of 1,4-
glycosidic linkages. This enzyme transfers the glucose from
UDP glucose to the non-reducing end of glycogen to form
a-1,4 linkages.
4. Formation of branches in glycogen
The formation of branches is brought about by the action of
a branching enzyme glucosyl a-(4–6) transferase. This
enzyme transfers a small fragment of five to eight glucose
residues from the non-reducing end of glycogen chain (by
breaking a-1,4 linkages) to another glucose residue where it
is linked by a-1,6 bond. This leads to the formation of a
new non-reducing end, besides the existing one. Glycogen
is further elongated and branched, respectively, by the
enzymes glycogen synthase and glucosyl 4–6 transferase.
The overall reaction of the glycogen synthesis for the
addition of each glucose residue is (Glucose)n 1 Glucose 1 2
ATP n (Glucose) n 1 11 2 ADP 1 Pi. Of the two ATP
utilized, one is required for the phosphorylation of glucose
while the other is needed for conversion of UDP to UTP.

SHORT ESSAYS
Fasting ,110 ,140 ,200
The diagnosis of diabetes can be made on the basis of 2 hours after ,160 .140 .200
individual’s response to the oral glucose load, commonly glucose
known as oral glucose tolerance test (OGTT) (Table 3.1.3). intake
PROCEDURE FOR GTT 250
Glucose tolerance test should be preferably conducted in
the morning (ideally from 9 to 11 am). A fasting blood
sample is drawn and urine should be collected. The subject
200
is then given 75 g of oral glucose dissolved in about 300
Markedly reduced glucose tolerance
mL of water, to drink in about 5 minutes. Blood and urine
Plasma glucose (mg/dL)

samples are collected at 30 minute intervals for at least 2

hours. All blood samples are subjected to glucose 150 Reduced glucose
estimation while urine samples are qualitatively tested for tolerance
glucose.
INTERPRETATION OF GTT
100
The graphic representation of the GTT results is depicted in
Fig. 3.1.7.
Normal glucose tolerance
The fasting plasma glucose level is ,100 mg/dL in normal
persons. On oral glucose load, the concentration increases 50
and the peak value (,150 mg/dL) is reached in less than an
hour, which returns to normal by 2 hours. Glucose is not
detected in any of the urine samples.
In individuals with impaired glucose tolerance, the fasting 012
(100–140 mg/dL) as well as 2 hour glucose levels (140– 1 Time (hours)
200 mg/dL) of plasma glucose levels are elevated. Fig. 3.1.7 Glucose Tolerance Curve
Table 3.1.3 Diagnostic criteria for oral glucose tolerance test Q. 2. Classification of carbohydrates.
(WHO 1985)
Plasma glucose concentration (mg/dL) CLASSIFICATION OF CARBOHYDRATES
Condition Impaired glucose
Normal tolerance Diabetes
262 Quick Review Series: BDS 1st Year
Carbohydrates are often referred to as saccharides. They are
broadly classified into three groups based on the number of
sugar units:
1. Monosaccharides 2. Oligosaccharides
3. Polysaccharides.
Monosaccharides and oligosaccharides are sweet to taste,
crystalline in character and soluble in water, hence they are
commonly known as sugars.
Monosaccharides
Monosaccharides (Greek: mono, meaning one) are often
referred to as simple sugars. They have the general formula
Cn(H2O)n, and cannot be further hydrolysed. The
monosaccharides are divided into different categories based
on the functional groups and the number of carbon atoms.
Aldoses: When the functional group in
monosaccharides is an aldehyde, they are known as aldoses,
for example glyceraldehydes and glucose.
Ketoses: When the functional group is a keto group,
they are referred to as ketoses, for example
dihydroxyacetone and fructose.
Based on the number of carbon atoms, the monosaccharides
are regarded as trioses (3C), tetroses (4C), pentoses (5C),
hexoses (6C) and heptoses (7C). These terms along with
functional groups are used while naming monosaccharides.
For instance, glucose is an aldohexose while fructose is a
ketohexose.
Oligosaccharides
Oligosaccharides (Greek: oligo, meaning few) contain 2–
10 monosaccharide molecules.
Based on the number of monosaccharide units present, the
oligosaccharides are subdivided into disaccharides,
trisaccharides, etc.
The disaccharides are of two types:
Reducing disaccharides — for example maltose and lactose.
Nonreducing disaccharides — for example sucrose and
trehalose.
Polysaccharides
Polysaccharides (Greek: poly, meaning many) are polymers
of monosaccharide units with high molecular weight. They
are usually tasteless (non-sugars) and form colloids with
water. Polysaccharides are of two types:
Homopolysaccharides — for example starch (glucan)
SHORT NOTES
cellulose, inulin (fructosan) and glycogen
Heteropolysaccharides—for example mucopolysaccharides,
hyaluronic acid and chondroitin sulphate.
Q. 3. Structure and biomedical importance of
disaccharides.
Q. 1. Glucose tolerance test (GTT).
The GTT means glucose tolerance test. The diagnosis of
diabetes can be made on the basis of individual’s response
Among the oligosaccharides, disaccharides are the most
common. A disaccharide consists of two monosaccharide
units, which may be similar or dissimilar, held together by a
glycosidic bond. They are crystalline, water soluble and
sweet to taste.
The disaccharides are of two types:
Reducing: Disaccharides with free aldehyde or keto
group — for example maltose and lactose.
Non-reducing: Disaccharides with no free aldehyde or
keto group — for example sucrose and trehalose.
Maltose
Maltose is composed of two a-D-glucose units held
together by a-(1–4) glycosidic linkage. The free aldehyde
group present on C1 of second glucose is responsible for
exhibiting all the properties of aldehyde group like the
osazones formation (sunflower-shaped), reduction of cupric
salts, etc.
Maltose or malt sugar (C12H22O11) is not found in free form
in the body. It is produced during the course of digestion of
starches by the enzyme amylase (pancreatic). Maltose can
be hydrolysed by dilute acid or the enzyme maltase to
liberate two molecules of a-D-glucose.
Sucrose
Sucrose (cane sugar) is mostly produced by sugar cane,
sugar beets and several ripe fruits. Sucrose is made up of a-
D-glucose and b-D-fructose. The two monosaccharides are
held together by a glycosidic linkage (a1–b2) between C1 of
a-glucose and C2 of fructose. The reducing groups of
glucose and fructose are involved in glycosidic bond.
Therefore, there is no free aldehyde or keto group in
sucrose, hence sucrose is a non-reducing sugar and cannot
form osazones. The phenomenon by which the
dextrorotatory sucrose is converted to levorotatory mixture
of glucose and fructose is known as ‘inversion’ and sucrose
is called the ‘invert sugar’.
Lactose
Lactose is more commonly known as milk sugar because it
is the disaccharide found in milk. Lactose of milk is the
most important carbohydrate in the nutrition of mammals.
Lactose is composed of b-D-galactose and b-D-glucose
held
together
by b-(1–
4) glycosidic linkage. The anomeric carbon of C 1 glucose is
free; hence lactose exhibits reducing properties and forms
osazones of powder-puff or hedgehog shape. It is
hydrolysed by the intestinal enzyme lactase to glucose and
galactose.
to the oral glucose load, commonly referred to as oral
glucose tolerance test (OGTT).
In the normal persons, the fasting plasma glucose level is
,100 mg/dL; on oral glucose load, the concentration

increases and the peak value ,150 mg/dL is reached in less
than an hour, which returns to normal by 2 hours. In
individuals with impaired glucose tolerance, the fasting
(100– 140 mg/dL) as well as 2 hour glucose levels (140–
200 mg/dL) of plasma glucose levels are elevated. Q. 2.
Glycosuria.
Normal urine does not contain reducing substances in urine
that can be detected by the usual tests such as the
Benedict’s. Presence of detectable amount of glucose,
fructose or pentose is therefore abnormal and is called
glycosuria.
Q. 3. What is glucosuria? Mention the normal renal
threshold for glucose.
Normal urine does not contain reducing substances in urine
that can be detected by the usual tests like the Benedict’s.
Presence of detectable amount of glucose, fructose or
pentose is therefore abnormal and is called glycosuria.
Excretion of glucose in urine may occur
In emotional states.
Following anaesthesia or asphyxia.
In severe hyperthyroidism.
In diabetes mellitus.
The most common cause of glucosuria is however diabetes
mellitus. The glucose concentration of urine in this
condition may vary from 0.5% to 12.0%. There is also
associated hyperglycaemia in conditions of diminished
renal threshold for glucose because of a defect in the
reabsorption of glucose levels. The condition is called renal
glycosuria (glucosuria). Fifteen percent of pregnant women
also show glucosuria without hyperglycaemia. Q. 4.
Glycolysis.
Glycolysis is defined as the sequence of reactions
converting glucose (or glycogen) to pyruvate or lactate,
with the production of ATP.
Q. 5. Significance of glycolysis.
The significance of glycolysis is as follows:
Under anaerobic conditions (lack of O2), pyruvate is
reduced by NADH to lactate in presence of the enzyme
lactate dehydrogenase. The formation of lactate allows the
regeneration of NAD1, which can be reused by
glyceraldehyde 3-phosphate dehydrogenase so that
glycolysis proceeds even in the absence of oxygen to
supply ATP.
The occurrence of uninterrupted glycolysis is very essential
in skeletal muscle during strenuous exercise when oxygen
supply is very limited.
Glycolysis in the erythrocytes leads to lactate production
because mitochondria — the centres for aerobic oxidation
— are absent.
Biochemistry 263
Brain, retina, skin, renal medulla and gastrointestinal tract
derive most of their energy from glycolysis.
Q. 6. What is meant by substrate-level
phosphorylation? Give one example.
Refer to the answer of Long Essays Q. 2.
Q. 7. How many ATP molecules are produced in
anaerobic glycolysis and aerobic glycolysis?
Under anaerobic conditions, two ATPs are synthesized
while, under aerobic conditions, eight or six ATP are
synthesized — depending on the shuttle pathway that
operates. Q. 8. Citric acid cycle.
The citric acid cycle (Krebs cycle or tricarboxylic acid
[TCA] cycle) is the most important metabolic pathway for
the energy supply to the body. About 65–70% of the ATP is
synthesized in Krebs cycle.
Citric acid cycle essentially involves the oxidation of acetyl
CoA to CO2 and H2O. This cycle utilizes about two-thirds
of total oxygen consumed by the body. The name TCA
cycle is used because at the outset of the cycle,
tricarboxylic acids (citrate, cis-aconitate and isocitrate)
participate.
Q. 9. Significance of TCA cycle.
The citric acid cycle is the final common oxidative pathway
for carbohydrates, fats and amino acids. This cycle not only
supplies energy but also provides many intermediates
required for the synthesis of amino acids, glucose, heme,
etc. Krebs cycle is the most important central pathway
connecting almost all the individual metabolic pathways
(either directly or indirectly).
The enzymes of TCA cycle are located in mitochondrial
matrix, in close proximity to the electron transport chain.
Q. 10. Name four mucopolysaccharides in the
body. Or
List four examples of mucopolysaccharides.
Or
Name three glycosaminoglycans
(mucopolysaccha-rides) in the body. Mention their
significance.
These are heteroglycans made up of repeating units of sugar
derivates, namely amino sugars and uronic acids.
GLYCOSAMINOGLYCANS
Mucopolysaccharides are more commonly known as
glycosaminoglycans (GAG). Acetylated amino groups,
besides sulphate and carboxyl groups, are generally present
in GAG structure.
The important mucopolysaccharides include the following:
1. Hyaluronic acid
Chondroitin 4-sulphate
Heparin 4. Dermatan sulphate
262 Quick Review Series: BDS 1st Year

5. Keratan sulphate. The anomeric carbon of glucose is free; hence lactose

SIGNIFICANCE OF MUCOPOLYSACCHARIDES exhibits reducing properties and forms osazones, powder-
Hyaluronic acid: Hyaluronic acid is an important puff or hedgehog shape.
GAG found in the ground substance of synovial fluid of Lactose of milk is the most important carbohydrate in the
joints and vitreous humour of eyes. It serves as a lubricant nutrition of young mammals. It is hydrolysed by the
and shock absorbent in joints. intestinal enzyme lactase to glucose and galactose.
It is also present as a ground substance in connective tissues Q. 14. Name the key enzymes of gluconeogenesis.
and forms a gel around the ovum.
Chondroitin 4-sulphate: It is a major constituent The key enzymes of gluconeogenesis are as follows:
of various mammalian tissues bone, cartilage, tendons, Pyruvate carboxylase
heart, valves, skin, cornea, etc. Fructose 1,6-bisphosphatase
Heparin: Heparin is an anticoagulant that occurs in Glucose 6-phosphatase. Q. 15. Mutarotation.
blood, lung, liver, kidney, spleen, etc. Heparin helps in the
release of the enzyme lipoprotein lipase, which causes Mutarotation is defined as the change in the specific optical
clearing of the turbidity of lipemic plasma. rotation representing the interconversion of a and b forms
Q. 11. Composition and functions of two of D-glucose to an equilibrium mixture.
homopolysaccharides. The a and b anomers of glucose have different optical
rotations. The specific optical rotation of a freshly prepared
STARCH glucose (a anomer) solution in water is 1112.2°, which
Starch is the carbohydrate reserve of plants, which is the gradually changes and attains equilibrium with a constant
most important dietary source for higher animals, including value of 152.7°.
man. High content of starch is found in cereals, roots, In the presence of alkali, the decrease in optical rotation is
tubers, vegetables, etc. Starch is a homopolymer composed rapid. The optical rotation of b-glucose is 118.7°.
of D-glucose units held by a-glycosidic bonds. It is known Mutarotation is summarized below:
as glucosan or glucan.
α-D-Glucose Equilibrium mixture β-D-Glucose
Starch consists of two polysaccharide components —
water-soluble amylose (15–20%) and a water-insoluble
amylopectin (80–85%).
INULIN
Inulin is a polymer of fructose, i.e. is fructosan. It occurs in
dahlia bulbs, garlic, onion, etc. It is a low-molecular-weight
(around 5000) polysaccharide, easily soluble in water.
Inulin is not utilized by the body. It is used for assessing
kidney function through measurement of glomerular
filtration rate (GFR).
Q. 12. What is cane sugar? Mention its
composition.

Sucrose is known as cane sugar and is the sugar of

commerce, mostly produced by sugar cane and sugar beets.
Sucrose is made up of a-D-glucose and b-D-fructose. The
two monosaccharides are held together by a glycosidic
bond a, —. b2 between C1 of a-glucose and C2 of b-fructose.
The reducing groups of glucose and fructose are involved in
glycosidic bond, hence sucrose is a non- reducing sugar and
cannot form osazones.
Q. 13. What is milk sugar? Mention its
composition.

Lactose is more commonly known as milk sugar because it

is the disaccharide found in milk.
Lactose is composed of b-D-galactose and b-D-glucose
held together by b-(1-4) glycosidic bond.
 Biochemistry 263

+ 112.2° + 52.7° + 18.7°

Carbamoyl phosphate limiting
synthetase
NH3 + CO2 Carbamoyl phosphate reaction.
2ATP N-acetylglutamate 2ADP - Pi CPS I
Mg2−
requires
N-

Ornithine
transcarbamoylase

Pi
Ornithine

Citrulline

Topic 2 CHEMISTRY AND METABOLISM OF

Urea

AMINO ACIDS AND PROTEINS ATP L-Asparate

acid
Arginase

LONG ESSAY Arginosuccinic

H2O Mg2+ acid synthetase

AMP + PP

Arginosuccinate
Arginine

Fumarate
Arginosuccinase
Fig. 3.2.1 Urea cycle.
Q. 1. Describe the urea cycle and its disorders. Or acetylglutamate for its activity.
Describe the urea cycle and list two disorders of CO2 + NH3 N-AcetylglutamateCPS Carbomoyl
urea cycle. phosphate
2ATP 2ADP + Pi
Urea cycle is the process by which ammonia, a highly toxic Formation of citrulline: Citrulline is
substance, is converted to urea, a less toxic and water- synthesized from carbamoyl phosphate and ornithine by
soluble excretory product in the liver (Fig.3.2.1). ornithine transcarbamoylase. Carbamoyl group is
Urea is synthesized in liver and transported to kidneys for transferred from carbamoyl phosphate to ornithine to
excretion in urine. Urea cycle is the first metabolic cycle produce citrulline.
that was elucidated by Hans Krebs and Kurt Henseleit Carbamoyl phosphate + OrnithineOrnithine transcarbamoylase
(1932), hence it is known as Krebs–Henseleit cycle. Citrulline Pi
Urea has two amino (—NH2) groups—one derived from Synthesis of arginosuccinate: Citrulline
NH3 and the other from aspartate. Carbon atom is supplied condenses with aspartate in the presence of arginosuccinate
by CO2. Urea synthesis is a five-step cyclic process, with synthase to produce arginosuccinate. This step requires
five distinct enzymes. The first two enzymes are present in ATP, which is cleaved to AMP and pyrophosphate (PPi).
mitochondria, while the rest are localized in cytosol. The second amino group of urea is added in this reaction.
STEPS IN THE UREA CYCLE Arginosuccinic acid
synthetase
Synthesis of carbamoyl phosphate: Citrulline + Aspartate Arginosuccinate
This step occurs in mitochondria, where carbamoyl ATP AMP + PP
phosphate synthase I (CPS I) catalyses the condensation of Cleavage of arginosuccinate:
NH41 ions with CO2 to form carbamoyl phosphate. This step Arginosuccinase hydrolyses arginosuccinate to
consumes two ATP and is irreversible as well as rate- arginine and fumarate. Arginine is the immediate precursor
262 Quick Review Series: BDS 1st Year

for urea. Fumarate enters mitochondria and is metabolized Carbamoyl phosphate synthetase is dependent on N-
to oxaloacetate through TCA cycle. acetylglutamate, which acts as allosteric activator for the
Arginosuccinase enzyme.
Arginosuccinate Arginine Fumarate Induction of urea cycle enzymes occurs when delivery of
Formation of urea: The enzyme arginase ammonia or amino acids to the liver is increased; thus, a
hydrolyses arginine to urea and ornithine. Ornithine, so high-protein diet or starvation results in the induction of
regenerated, enters mitochondria for its reuse in the urea enzymes of urea cycle.
cycle. Arginase METABOLIC DISORDERS OF UREA CYCLE
Metabolic defects associated with all the five enzymes of
Arginine Ornithine urea cycle are listed in Table 3.2.1.
H 2O Urea Table 3.2.1 Metabolic disorders of urea cycle
OVERALL REACTION AND ENERGETICS Metabolic disorder Deficient enzymes
The urea cycle consumes four ATPs and is irreversible. involved
Two ATPs are utilized for the synthesis of carbamoyl Hyperammonaemia type I Carbamoyl phosphate
phosphate. One ATP is converted to AMP and PPi to synthase I
produce arginosuccinate, which equalizes to two ATPs. Hyperammonaemia type II Ornithine transcarbamoylase
Hence four ATPs are actually consumed. Citrullinemia Arginosuccinic acid synthase
NH41 1 CO2 1 Aspartate 1 3ATP n Urea 1 Fumarate 1 Arginosuccinic aciduria Arginosuccinase
2ADP 1 2Pi 1 AMP 1 PPi Hyperargininemia Arginase
REGULATION OF UREA CYCLE The clinical symptoms associated with defect in urea cycle
The first reaction catalysed by carbamoyl phosphate enzymes include vomiting, lethargy, irritability, ataxia and
synthase I (CPS I) is rate-limiting reaction or committed mental retardation.
step in urea synthesis. CPS I is allosterically activated by All the disorders invariably lead to a build-up of ammonia
N-acetylglutamate (NAG). in blood (hyperammonaemia), leading to toxicity.
Depending on the specific enzyme defect, other metabolites
of urea cycle also accumulate.
Q. 1. Denaturation of proteins. Denatured protein is more easily digested. This is due to
increased exposure of peptide bonds to enzymes. Cooking
The phenomenon of disorganization of native protein causes protein denaturation, and, therefore, cooked protein
structure is known as denaturation. Denaturation results in food is more easily digested.
the loss of secondary, tertiary and quaternary structure of Denaturation is usually irreversible.
proteins. This involves a change in physical, chemical and Q. 2. How is creatine-P synthesized?
biological properties of protein molecules.
AGENTS OF DENATURATION Creatine is present in the tissues (muscle, brain, blood, etc.)
Physical Agents as the high-energy compound phosphocreatine and as free
Heat creatine.
Violent shaking Three amino acids — glycine, arginine and methionine are
X-rays required for creatine formation.
UV radiation The first reaction occurs in the kidney, which involves the
Chemical Agents transfer of guanidino group of arginine to glycine, catalysed
Acids by arginine–glycine transaminase to produce
Alkalies guanidinoacetate (glycocyamine).
Organic solvents (ether, alcohol) S-adenosylmethionine (active methionine) donates methyl
Salts of heavy metals (Pb, Hg) group to glycocyamine to produce creatine. This reaction
Urea occurs in liver. Creatine is reversibly phosphorylated to
Salicylate phosphocreatine (creatine phosphate) by creatine kinase. It
CHARACTERISTICS OF DENATURATION is stored in muscle as high-energy phosphate.
The native helical structure of protein is lost. Q. 3. Substance formed from tyrosine.
The primary structure of a protein with peptide linkages
remains intact, i.e. peptide bonds are not hydrolysed. Tyrosine is the precursor for melanin.
The protein loses its biological activity. Melanin is the pigment of skin, hair and eye. The synthesis
Denatured protein becomes insoluble in the solvent in of melanin occurs in melanosomes present in melanocytes
which it was originally soluble. — the pigment-producing cells.

SHORT ESSAYS
 Biochemistry 263

Tyrosinase hydroxylates tyrosine to form 3,4-
dihydroxyphenylalanine (DOPA). DOPA can act as a
cofactor for tyrosinase. DOPA is then converted to
dopaquinone.
The subsequent couple of reactions occur spontaneously,
forming leucodopachrome followed by 5,6-
dihydroxyindole. The oxidation of 5,6-dihydroxyindole to
indole 5,6-quinone is catalysed by tyrosinase, and DOPA
serves as a cofactor. This reaction, inhibited by tyrosine
regulates the synthesis of melanin, as shown in Fig. 3.2.2.
Q. 4. What are conjugated proteins? Give three
examples.
The conjugated proteins contain a non-protein moiety
known as prosthetic group or conjugating group in addition
to amino acids.
The conjugated proteins are subdivided into different
groups as follows:
Nucleoproteins are conjugated proteins having nucleic
acids as their prosthetic groups, e.g. protamines and
histones.
Nucleoprotein is present in every living cell as well as in
viruses and bacteriophage, and is the essential constituent
of the genes.
Proteoglycans and glycoproteins: Proteins
conjugated with mucopolysaccharides are called
‘proteoglycans’, e.g. gastric and salivary mucins,
immunoglobulins, human chorionic gonadotropins,
erythrocyte and lymphocyte cell membrane proteins
Chromoproteins: The prosthetic group is a coloured
compound; haemoglobin, flavoprotein and visual purple are
a few examples.
Lipoproteins: Protein is combined with phospholipids,
e.g. lipoproteins occur in milk, blood serum, egg yolk and
others.
They are also important constituents of the cell membranes.
Q. 5. Primary and secondary structure of proteins.
Proteins are the polymers of L-alpha-amino acids. The
structure of proteins is rather complex, which can be
divided into four levels of organization:
1. Primary structure: The linear sequence of
amino acids forming the backbone of proteins
(polypeptides).
2

2. Secondary structure: The spatial arrangement of protein by twisting of the polypeptide

chain. 3. Tertiary structure: The three-dimensional structure of
Tyrosine
Oa functional protein. Melanochrome
Melanin polymers Black
Tyrosinase 4. Quaternary structure: Some of the proteins are com- Fig 3.2.2 Synthesis
H Oposed of two or more polypeptide chains referred to as
2 of melanin.
3, 4-Dihydroxyphenylalanine (DOPA) subunits. The spatial arrangement of these subunits is H2N–CH–CO–NH–
CH–CO–NH–CH–CO
Oknown as quaternary structure.
—NH–CH–COOH
Tyrosinase H2O
PRIMARY STRUCTURE OF PROTEIN
Dopaquinone
The primary structure of a protein is largely responsible
Nonenzymatic for its function.
Leukodopachrome
Primary structure of a protein refers to the order and sequence of amino acid residues.
5, 6-Dihydroxyindole 3. Some proteins are synthesized as single polypeptides
Othat are later cleaved into two or more chains, such as
Tyrosinase insulin. Then proteins have intrachain as well as inter-
H O chain disulphide linkages, as shown in Fig. 3.2.3.
2

Indole 5-6-quinone
262 Quick Review Series: BDS 1st Year

R1 R2 R3 R4
Fig. 3.2.3 The primary structure of
a protein.
4. A pure sample of a protein or a
CO
polypeptide is essential for the
determination of primary
structure, which involves three NH
stages:
Determination of amino acid
composition
Degradation of protein or
polypeptide into smaller
fragments
Determination of the amino acid
sequence.
SECONDARY STRUCTURE
OF PROTEIN
The amino acids are located close
to each other in their sequence. The salient features of a-helix are as follows:
Two types of secondary The a-helix is a tightly packed coiled structure with
structures mainly identified are a- amino acid side chains extending outward from the
helix and b-sheet. central axis.
Secondary level of protein The a-helix is stabilized by extensive hydrogen bonding.
structure includes folding and It is formed between H atom attached to peptide N, and
twisting patterns of polypeptide O atom attached to peptide C. The hydrogen bonds are
chains, i.e. the local spatial individually weak but collectively, they are strong
arrangement of a polypeptide. enough to stabilize the helix.
Secondary structures include a- All the peptide bonds except the first and last in a
helix and b-sheet structures: a- polypeptide chain participate in hydrogen bonding.
HELIX Each turn of a-helix contains 3.6 amino acids and travels
a-Helical structure was proposed a distance of 0.54 nm. The spacing of each amino acid is
by Pauling and Corey (1951). a- 0.15 nm.
Helix is the most common spiral a-Helix is a stable conformation formed spontaneously
structure of protein (Fig. 3.2.4). It with the lowest energy.
has a rigid arrangement of The right-handed a-helix is more stable than lefthanded
polypeptide chain. helix.
b-PLEATED SHEET (FIG. 3.2.5)

Fig. 3.2.4 Secondary structure of protein.

Fig. 3.2.5 b-Pleated sheet.
This is the second type of structure proposed by Pauling and Corey. b-Pleated sheets (or simply b-sheets) are composed of
two or more segments of fully extended peptide chains. In the b-sheets, the hydrogen bonds are formed between, the
neighbouring segments of polypeptide chain(s). Q. 6. Describe urea cycle.
 Biochemistry 263

Refer to the Answer of Long Essays Q. 1.

SHORT NOTES
Q. 1. Active methionine. Methionine is an essential amino acid. It is glycogenic.
Methionine is particularly important as a donor of methyl
group in reactions known as transmethylation reactions.
Active methionine: To act as methyl donor, the amino AGENTS OF DENATURATION
acid has to be first activated by ATP. Physical agents: Heat, X-rays, UV radiation Chemical
Activating enzyme agents: Acids, alkalies, organic solvents (ether, alcohol),
Methionine + ATPactive methionine + PP + P salts of heavy metals (Pb, Hg), urea, salicylate. Q. 4.
(Liver) Classification of proteins.
Active methionine or adenosyl-S-methionine has the
following structure: Proteins are classified in several ways. Three major types of
CH3 Adenine-ribose-S-CH2 CH2 CHNH2 COOH classifying proteins based on their function, chemical
The S,methyl bond is a high-energy bond. The nature, solubility properties and nutritional importance are
methyl group is hence labile and can be readily transferred discussed here.
to an acceptor. The activating enzyme is known as A. FUNCTIONAL CLASSIFICATION OF PROTEINS
methionineadenosyl transferase. Based on the function they perform, proteins are classified
Q. 2. Essential amino acids. Or in the following groups
Name essential amino acids and discuss their Structural proteins, e.g. keratin of hair and nails, collagen of
functions. bone.
Enzymes or catalytic proteins, e.g. hexokinase, pepsin.
Amino acids are grouped into two classes: Transport proteins, e.g. haemoglobin, serum albumin.
1. Essential amino acids 2. Non-essential amino acids. Hormonal proteins, e.g. insulin, growth hormone.
Essential or indispensable amino acids: Contractile proteins, e.g. actin, myosin.
The amino acids which cannot be synthesized by Storage proteins, e.g. ovalbumin, glutelin.
the body and, therefore, need to be supplied through the diet Genetic proteins, e.g. nucleoproteins.
are called essential amino acids. They are required for Defence proteins, e.g. snake venoms, immunoglobulins.
proper growth and maintenance of the individual. The 10 Receptor proteins, e.g. for hormones, viruses.
amino acids listed below are essential for hum B. PROTEIN CLASSIFICATION BASED ON
Arginine CHEMICAL NATURE AND SOLUBILITY
Valine This is a more comprehensive and popular classification of
Histidine proteins. It is based on the amino acid composition,
Isoleucine structure, shape and solubility properties. Proteins are
Leucine broadly classified into three major groups.
Lysine Simple proteins: They are composed of only amino
Methionine acid residues.
Phenylalanine 9. Threonine 1 0. Tryptophan. Albumins: Soluble proteins present in serum, milk,
Of the ten listed above, two amino acids namely arginine egg, etc.
and histidine can be partly synthesized by adult humans, Globulins: Sparingly soluble proteins present in
hence these are considered as semiessential. Thus, eight serum, milk and egg.
amino acids are absolutely essential while two are Prolamines: Example, gliadin of wheat or zein of
semiessential. maize.
The nutritional importance of proteins is based on the Glutelins: Example, glutenin of wheat or oryzenin of
content of essential amino acids. rice.
Q. 3. Denaturation of proteins. Scleroproteins: These are also found in bone cartilage and
protective tissues like skin, nail, etc.
The phenomenon of disorganization of native protein Histones: Example, nucleohistones.
structure is known as denaturation. Denaturation results Conjugated proteins: Besides the amino acids,
in the loss of secondary, tertiary and quaternary structure of these proteins contain a non-protein moiety known as
proteins. prosthetic group or conjugating group, e.g. nucleoproteins,
This involves a change in physical, chemical and biological lipoproteins, etc.
properties of protein molecules.
262 Quick Review Series: BDS 1st Year
Derivedproteins: These are the denatured or
degraded products of simple and conjugated proteins or
those produced by change of peptide bonds.
They are further classified as primary and secondary
derived proteins.
C. NUTRITIONAL CLASSIFICATION OF PROTEINS
The nutritive value of proteins is determined by the
composition of essential amino acids. From the nutritional
point of view, proteins are classified into three categories:
Complete proteins: Simple proteins
conjugated with a non-protien substance called as a
prosthetic group are referred to as conjugated proteins, e.g.
nucleoproteins, glycoproteins, phosphoproteins,
lipoproteins. These proteins have all the 10 essential amino
acids in the required proportion by the human body to
promote good growth, e.g. egg albumin, milk casein.
Partially incomplete proteins: These
proteins are partially lacking one or more essential amino
acids and hence can promote moderate growth, e.g. wheat
and rice proteins.
Incomplete proteins: These proteins
completely lack one or more essential amino acids. Hence,
they do not promote growth at all, e.g. gelatin. Q. 5.
Functions of lipoproteins.
Lipoproteins are molecular complexes that consist of lipids
and proteins, i.e. conjugated proteins.
They function as transport vehicles for lipids in blood
plasma.
Lipoproteins deliver the lipid components (cholesterol,
triacylglycerol etc.) to various tissues for utilization.
CLASSIFICATION OF LIPOPROTEINS AND THEIR
FUNCTIONS
Five major classes of lipoproteins are identified in human
plasma, based on their separation by electrophoresis.
Chylomicrons: They are synthesized in the intestine and
transport exogenous (dietary) triacylglycerol to various
tissues. They consist of highest (99%) quantity of lipid and
lowest (1%) concentration of protein.
Very low-density lipoproteins (VLDL):
They are produced in liver and intestine, and are
responsible for the transport of endogenously synthesized
triacylglycerols.
Low-density lipoproteins (LDL): They are formed
from VLDL in the blood circulation. They transport
cholesterol from liver to other tissues.
High-density lipoproteins (HDL): They are mostly
synthesized in liver. Three different fractions of HDL (1, 2
and 3) can be identified by ultracentrifugation. HDL
particles transport cholesterol from peripheral tissues to
liver (reverse cholesterol transport).
Free fatty acids — albumin: Free
fatty acids in the circulation are in a bound form to albumin.
Each molecule of albumin can hold about 20–30 molecules
of free fatty acids.
Q. 6. Primary structure of protein.
Proteins are the polymers of L-alpha-amino acids. The
structure of proteins is rather complex, which can be
divided into four levels of organization: 1. Primary
structure
Secondary structure
Tertiary structure 4. Quaternary structure.
Primary Structure: The linear sequence of
amino acids forming the backbone of proteins
(polypeptides) is known as primary structure of proteins.
The primary structure of a protein is largely responsible for
its function. Q. 7. Biological value of proteins.
Biological value is one of the methods employed to assess
the nutritive value of proteins.
Biological value of certain food proteins are as follows:
Egg 94
Milk 84
Fish 85
Meat 75
Rice 68
Wheat 58
Soya bean 65
Q. 8. What are zwitter ions?
The name zwitter is derived from the German word, which
means hybrid. Zwitter ion (or dipolar ion) is a hybrid
molecule containing positive and negative ionic groups.
The amino acids rarely exist in a neutral form with free
carboxylic (—COOH) and free amino –NH 2 groups. In
strongly acidic pH (low pH), the amino acid is positively
charged (cation), while in strongly alkaline pH (high pH), it
is negatively charged (anion). Each amino acid has a
characteristic pH (e.g. leucine, pH 6.0) at which it carries
both positive and negative charges, and exists as zwitter
ion.
Q. 9. What are nucleosides and nucleotides? Give
examples of each one.
Nucleic acids are the polymers of nucleotides. Nucleotides
are composed of a nitrogenous base, a pentose sugar and a
phosphate. Nucleotides perform a wide variety of functions
in the living cells.
The term nucleoside refers to base 1 sugar. Nucleotide is a
nucleoside 1 phosphate.
The addition of a pentose sugar to base produces a
nucleoside. If the sugar is ribose, ribonucleosides are
 Biochemistry 263

formed. Adenosine, guanosine, cytidine and uridine are the 5. Tyrosinosis or tyrosinaemia type I
ribonucleosides of A, G, C and U, respectively. This is due to the deficiency of the enzymes
If the sugar is a deoxyribose, deoxyribonucleosides are fumarylacetoacetate hydroxylase and/or
produced. maleylacetoacetate isomerase. Tyrosinosis is a rare but
The term mononucleotide is used when a single phosphate serious disorder.
moiety is added to a nucleoside. Thus adenosine 6. Albinism
monophosphate (AMP) contains adenine 1 ribose 1 Albinism (Greek: albino — white) is an inborn error due to
phosphate. Example 1 of Nucleoside the lack of synthesis of the pigment melanin.
Base Ribonucleosid Ribonucleotide Abbreviatio The most common cause of albinism is a defect in
e (5’- n tyrosinase— the enzyme most responsible for the synthesis
monophosphate of melanin.
)
Q. 11. Name different types of RNA and their
Adenine(A Adenosine Adenosine 5’- AMP functions.
) monophosphate
or adenylate
The three distinct types of RNAs with their respective
Example 2 of Nucleoside
cellular composition are given below: 1. Messenger RNA
Base Deoxyribonucleosi Deoxyribonucleoti Abbreviati
de de (5’- on
(mRNA): 5–10%
monophosphate) 2. Transfer RNA (tRNA): 10–20% 3. Ribosomal RNA
Adenine( Deoxyadenosine Deoxyadenosine dAMP (rRNA): 50–80%.
A) 5’- Besides the three RNAs referred above, human cells also
monophosphate contain small nuclear RNA (snRNA), which is involved in
or RNA processing.
deoxyadenylate Messenger RNA (mRNA): The specific
Q. 10. Name the inborn errors of metabolism in information required for the synthesis of a given protein is
phenylalanine pathway and mention the enzymes present on the mRNA.
that are missing in each case. Transfer RNAs (tRNAs): They carry the
amino acids and hand over them to the growing peptide
DISORDERS OF TYROSINE (PHENYLALANINE) chain.
METABOLISM Ribosomal RNA (rRNA): The function of
Several enzyme defects in phenylalanine/tyrosine RNAs in ribosomes is not clearly known. It is believed that
degradation leading to metabolic disorders are known. The they play a significant role in the binding of mRNA to
deficient enzymes and the respective inborn errors are ribosomes and protein synthesis.
discussed below: Q. 12. Structure and functions of M-RNA.
1. Phenylketonuria
Phenylketonuria (PKU) is the most common metabolic The mRNA is synthesized in the nucleus (in eukaryotes) as
disorder in amino acid metabolism. The incidence of PKU heterogeneous nuclear RNA (hnRNA). hnRNA on
is 1 in 10,000 births. It is due to the deficiency of the processing liberates the functional mRNA, which enters the
hepatic enzyme phenylalanine hydroxylase caused by an cytoplasm to participate in protein synthesis. mRNA has
autosomal recessive gene. high molecular weight with short half-life.
2. Tyrosinaemia type II Cap Poly A tail
This disorder — also known as Richner–Hanhart Coding sequence Gppp
5´
syndrome, is due to a defect in the enzyme tyrosine pApApApApA·OH
3´
transaminase.
3. Neonatal tyrosinaemia
The absence of the enzyme p-hydroxyphenyl-pyruvate
dioxygenase causes neonatal tyrosinaemia. This is mostly a
temporary condition and usually responds to ascorbic acid.
4. Alkaptonuria
The defective enzyme in alkaptonuria is homogentisate
oxidase in tyrosine metabolism.
Alkaptonuria has great historical importance. It was first
described by Lusitanus in 1649 and characterized in 1859.
Garrod conceived the idea of inborn errors of metabolism
from his observation on alkaptonuria.
262 Quick Review Series: BDS 1st Year

STRUCTURE OF M-RNA specific or unambiguous, e.g. UGG is the codon for

The eukaryotic mRNA is capped at the 5’-terminal end by there are 61 codons available to code for only 20 amino
7-methylguanosine triphosphate. It is believed that this cap acids. For instance, glycine has four codons. Q. 15. Where
helps to prevent the hydrolysis of mRNA by 5’- is urea synthesized?
exonucleases. Further, the cap may be also involved in the
recognition of mRNA for protein synthesis. Urea is synthesized in liver and transported to kidneys for
The 3’-terminal end of mRNA contains a polymer of excretion in urine.
adenylate residues (20–250 nucleotides), which is known as Q. 16. Name three conjugated proteins and
poly (A) tail. This tail may provide stability to mRNA, discuss their significance.
besides preventing it from the attack of 3’-exonucleases. Or
mRNA molecules often contain certain modified bases Name four conjugated proteins and their
such as 6-methyladenylates in the internal structure. significance.
FUNCTIONS
The specific information required for the synthesis of a Definition: Besides the amino acids, these proteins
given protein is present on the mRNA. contain a non-protein moiety known as prosthetic group or
Q. 13. Significance of blood urea estimation. conjugating group.
Various conjugated proteins are as follows:
In healthy people, the normal blood urea concentration is Nucleoprotein is present in every living cell and is the
10–40 mg/dL. essential constituent of the genes.
Blood urea estimation is widely used as a screening test for Lipoproteins are important constituents of cell membranes.
the evaluation of kidney (renal) function. Chromoproteins, e.g. haemoglobin, flavoprotein and visual
Q. 14. Describe the features of genetic code. purple.
Metalloproteins: Fe, Co, Mn, Zn, Cu and Mg are some of
Definition: The three nucleotide (triplet) base the metallic ions associated with proteins. The proteins are
sequences in mRNA that act as code words for amino acids usually enzymes and require metallic ions as activators.
in protein, constitute the genetic code or simply codons. Glycoproteins: Protein conjugated with carbohydrates.
The genetic code may be regarded as a dictionary of Phosphoproteins: Phosphoric acid attached to serine and
nucleotide bases (A, G, C and U) that determines the threonine moieties of a protein, e.g. casein of milk.
sequence of amino acids in proteins. Mucoproteins.
The codons are composed of the four nucleotide bases, Q. 17. Protein–energy malnutrition. Or
namely the purines — adenine (A) and guanine (G), and the Protein–calorie malnutrition.
pyrimidines — cytosine (C) and uracil (U). These four
bases produce 64 different combinations (4 3) of three base Protein–energy malnutrition (PEM), sometimes called
codons. protein– calorie malnutrition (PCM), is the most common
The nucleotide sequence of the codon on mRNA is written nutritional disorder of the developing countries. PEM is
from the 5’-end to 3’ end. Sixty-one codons code for the 20 widely prevalent in the infants and preschool children.
amino acids found in protein. Kwashiorkor and marasmus are the two extreme forms of
Characteristics of genetic code are as follows: The genetic protein–energy malnutrition.
code is universal, specific, nonoverlapping and degenerate. Kwashiorkor literally means sickness of the deposed child,
Universality: The same codons are used to code for the i.e. a disease the child gets when the next baby is born. It is
same amino acids in all the living organisms. Hence, predominantly found in children between 1 and 5 years of
genetic code is appropriately regarded as universal. age. This is primarily due to insufficient intake of proteins.
Specificity: A particular codon always codes for the Marasmus literally means ‘to waste’. It mainly occurs in
same amino acid; hence the genetic code is highly children under 1 year of age. Marasmus is primarily due to
tryptophan. the deficiency of calories.
Nonoverlapping: The genetic code is read from a Q. 18. Four functions of plasma proteins.
fixed point as a continuous base sequence. It is
nonoverlapping, commaless and without any punctuations. Functions of plasma proteins are as follows:
For instance, UUUCUUAGAGGG is read as UUU/ Fluid exchange: Effective exchange of fluid
CUU/AGA/GGG. Addition or deletion of one or two bases between tissue spaces and plasma is thus maintained. In this
will radically change the message sequence in mRNA. function albumin plays a greater role than globulins.
Degenerate: Most of the amino acids have more than Buffering action: At pH 7.4 of blood, a plasma
one codon. The codon is degenerate or redundant, since protein acts as weak acid and combines with cations,
 Biochemistry 263

mainly sodium. This accounts for about 16 mEq/L (out of pair of keto acids, catalysed by a group of enzymes called
143 mEq/L). transaminases (recently, aminotransferases).
Reserveprotein: The plasma protein can be taken
up by tissues and used for the building up of tissue proteins
and vice versa.
Transport: Insoluble substances like bilirubin, steroid
and other hormones, fatty acids and other lipids and metals
are transported in plasma in loose combination with plasma
protein.
Q. 19. Transamination.

The transfer of an amino (–NH2) group from an amino acid

to a keto acid is known as transamination. This process
involves the interconversion of a pair of amino acids and a
Q. 1. Give an account of beta-oxidation of fatty phosphates are produced because ATP is converted to
acids, and give the energetics on oxidation of one pyrophosphate (PPi). The enzyme inorganic
molecule of palmitic acid. pyrophosphatase hydrolyzes PPi to phosphate (Pi). The
Or immediate elimination of PPi makes this reaction totally
Describe beta-oxidation of fatty acids and its irreversible.
energetics.

Topic 3 CHEMISTRY AND METABOLISM OF

LIPIDS
LONG ESSAYS
Or
Explain beta-oxidation of fatty acids. What is the
importance of this process?

The fatty acids in the body are mostly oxidized by b-

oxidation. b-Oxidation may be defined as the oxidation of
fatty acids on the b-carbon atom. This results in the
sequential removal of a two carbon fragment, acetyl CoA.
FATTY ACID OXIDATION: STAGES AND TISSUES
The b-oxidation of fatty acids involves three stages:
Activation of fatty acids occurring in the cytosol
Transport of fatty acids into mitochondria
b-Oxidation proper in the mitochondrial matrix.
Fatty acids are oxidized by most of the tissues in the body.
However, brain, erythrocytes and adrenal medulla cannot
utilize fatty acids for energy requirement.
The stages in b-oxidation of fatty acids are described in Fig.
3.3.1.
b-OXIDATION OF FATTY ACIDS
Palmitoyl CoA (16 carbon) undergoes seven cycles to yield
eight acetyl CoA [activation; transport and b-oxidation
proper—(1) oxidation, (2) hydration, (3) oxidation and (4)
cleavage].
Fatty acid activation
Fatty acids are activated to acyl CoA by thiokinases or acyl
CoA synthetases. In this reaction, two high-energy
R—CH2—CH2—CH2—C—O−
Fatty acid

ATP Mg2+ CoASH

I.
 O

R—CH2—CH2—CH2—C—SCoA
Acyl CoA
262 Quick Review Series: BDS 1st Year
Cytosol
II. Carnitine transport system
Mitochondrion
III.
O
formed between a- and b-carbons (i.e. two and three
β α
carbons).
R—CH2—CH2—CH2—C—SCoA
Hydration: Enoyl CoA hydratase brings about the
Acyl CoA
hydration of the double bond to form b-hydroxyacyl CoA.
2ATP
Oxidation: b-Hydroxyacyl-CoA dehydro genase
H2O catalyses the second oxidation and generates NADH. The
product formed is b-ketoacyl CoA.
Cleavage: The final reaction in b-oxidation is the
liberation of a two-carbon fragment, acetyl CoA from acyl
CoA. This occurs by a thiolytic cleavage catalysed by b-
ketoacyl CoA thiolase (or simply thiolase).
The new acyl CoA, containing two carbons less than the
original, re-enters the 3-oxidation cycle. The process
continues till the fatty acid is completely oxidized.
The scheme of fatty acid oxidation discussed above
3ATP
corresponds to saturated (no double bond) and even carbon
H2O fatty acids. This occurs most predominantly in biological
system.
Oxidation of palmitoyl CoA
The summary of 3-oxidation of palmitoyl CoA is shown
here under:
Palmitoyl Co A 1 7 Co ASH 1 7 FAD 1 7 NAD1 1 7 H20 n
8 Acetyl Co A 1 7 FADH2 1 7 NADH 1 7 H1
Palmitoyl CoA undergoes seven cycles of b-oxidation to
Transport of acyl CoA into mitochondria yield eight acetyl CoA. Acetyl CoA can enter citric acid
The inner mitochondrial membrane is impermeable to fatty cycle and get completely oxidized to CO2 and H2O.
acids. A specialized carnitine carrier system operates to Energetics of b-oxidation
O The ultimate aim of fatty acid oxidation is to generate
FAD Acyl CoA energy. The energy (net 129 ATPs) obtained from the
dehydrogenase FADH2
R—CH2—CH = CH—C—SCoA complete oxidation of palmitic acid (16 carbon) is given in
∆2 Trans-enoyl CoA O Table 3.3.1.
H2O Enoyl CoA Table 3.3.1 Energetics of palmitic acid oxidation
hydratase ATP
OH O Mechanism yield
R—CH2—CH—CH2—C—SCoA β-Hydroxyacyl CoA
NAD+ β-Hydroxyacyl CoA b-Oxidation seven cycles 14
dehydrogenase NAD H + H+ 7 FADH2 [oxidized by electron transport chain (ETC);
O O each
R—CH2—C—CH2—C—SCoA β-Ketoacyl CoA FADH2 gives 2 ATPs], 7 NADH (oxidized by ETC,
CoASH Thiolase2CO2 each NADH liberates 3 ATPs)
(4)
O From 8 acetyl CoA 21
R—CH2—C—SCoA + CH3—C—SCoA Oxidized by citric acid cycle, each acetyl CoA 96
Acyl CoA (−2C) Acetyl CoA provides 12 ATPs
Fig. 3.3.1 Stages in b-oxidation of fatty acids.
Total energy from one mole of palmitoyl CoA 131
transport activated fatty acids from cytosol to the
mitochondria. Energy utilized for activation (formation of palmitoyl –2
CoA)
b-Oxidation proper Krebs
Each cycle of b-oxidation, Net yield of oxidation of one molecule of palmitate 129
cycle
liberating a two-carbon unitacetyl O Oxidation of odd-carbon chain fatty acids
CoA, occurs in a sequence of four The b-oxidation of saturated fatty acids containing odd
reactions mentioned below: number of carbon atoms proceeds in the same manner, as
Oxidation: Acyl CoA described above for even carbon fatty acids. The only
undergoes dehydrogenation by an FAD-dependent difference is that in the last and final b-oxidation cycle, a
flavoenzyme, acyl CoA dehydrogenase. A double bond is three-carbon fragment is left behind (in place of two-carbon
 Biochemistry 263

unit for saturated fatty acids). This compound is propionyl
CoA, which is converted to succinyl CoA and metabolized.
Oxidation of unsaturated fatty acids
Because of the presence of double bonds, the unsaturated
fatty acids are not reduced to the same extent as saturated
fatty acids. Therefore, oxidation of unsaturated fatty acids,
in general, provides less energy than that of saturated fatty
acids.
Most of the reactions involved in the oxidation of
SHORT ESSAYS
unsaturated fatty acids are the same as found in the b-
oxidation of saturated fatty acids. However, the presence of
double bonds poses problem for b-oxidation to proceed.
This is overcome by two additional enzymes — an
isomerase and an epimerase. Q. 2. Name the different
pathways of fatty acid oxidation. How is palmitic
acid oxidized in the body? Write down the
energetics.
PATHWAYS OF FATTY ACID OXIDIZATION
Different pathways of fatty acid oxidation are as follows. b-
Oxidation of fatty acids
The fatty acids in the body are mostly oxidized by b-
oxidation. b-Oxidation may be defined as the oxidation of
fatty acids on the b-carbon atom. This results in the
sequential removal of a two-carbon fragment, acetyl CoA.
a-Oxidation of fatty acids
This is found to occur in the microsomal fraction of brain
and other tissues and plants. This particularly involves the
hydroxy fatty acids, where the -OH is attached to the a-
Q. 1. Essential fatty acids.
Cholesterol
NADPH + H+
+ O2
7-α -Hydroxylase
NADP+
7-Hydroxycholesterol
carbon. One carbon is removed at a time starting from the -
COOH end. It does not require coenzyme A and does not
generate ATP. v-Oxidation b
This is observed in the liver microsomal fraction. Medium-
chain-length fatty acids are usually involved. First an -OH
is added to the omega carbon, which is then further
oxidized to form an a-v-dicarboxylic acid. Now b-oxidation
can occur from either end.
Palmitic acid is oxidized by b-oxidation; it will run through
b-oxidation cycle seven times. Refer to the answer of Long
Essays Q. 1 for b-oxidation cycle.
Energetics of palmitic acid oxidation
If palmitic acid is oxidized, it will result in eight molecules
of acetate and will run through b-oxidation cycle seven
times. In each cycle of b-oxidation, energy can be obtained
by reoxidation of the coenzymes FADH2 (step 2) and
NADH 1 H1 (step 4), the first yielding two ATPs and the
second, three ATPs. Thus, a total of five ATPs is realized
when a fatty acid runs through the cycle once.
Because palmitic acid runs seven times, energy by b-
oxidation 7 3 5 5 35 ATPs.
Each of the eight molecules of acetate when oxidized in
citric acid cycle will produce 8 3 12 5 96 ATPs
Total 5 131 ATPs
In the initial activation step of fatty acid, one ATP is
converted to AMP 1 PP, resulting in loss of two energy-rich
phosphates. That is (2)2 ATPs.
Hence, the net gain 5 129 ATPs.
The fatty acids that cannot be synthesized by the body and,
therefore, should be supplied in the diet are known as
essential fatty acids (EFA).
Chemically, they are polyunsaturated fatty acids, namely
linoleic acid (18:2; 9, 12), linolenic acid (18:3; 9, 12, 15),
and arachidonic acid.
Essential fatty acids are required for the membrane
structure and function, transport of cholesterol, formation of
lipoproteins, prevention of fatty liver, etc. They
are also needed for the synthesis of another important group
of compounds, namely eicosanoids.
The deficiency of EFA results in phrynoderma or toad skin.
Q. 2. Cholesterol degradation.

Several Several
The steroid nucleus (the ring structure) of the cholesterol
steps steps cannot be degraded to CO2 and H2O.
Cholesterol (50%) is converted to bile acids, excreted in
Cholic acid Chenodeoxycholic
faeces, and serves as a precursor for the synthesis of steroid
Glycine acid hormones, vitamin D, coprostanol and cholestanol.
glycine
acid** Intestinal
Taurine O
Taurine Fig. 3.3.2 Synthesis of bile acids. (Note: *primary bile acids; **
Glycocholic secondary bile acids).
acid*
Tauro- or
Intestinal glycochenodeoxycholic
bacteria acid*
Taurocholic
 bacteria

Lithocholic acid**
262 Quick Review Series: BDS 1st Year

SYNTHESIS OF BILE ACIDS (FIG. 3.3.2) A brief outline of steroid hormonal synthesis is given in
The synthesis of primary bile acids takes place in the liver Fig. 3.3.3.
and involves a series of reactions. Colic acid and SYNTHESIS OF VITAMIN D
chenodeoxycholic acid are the primary bile acids, and the 7-Dehydrocholesterol, an intermediate in the synthesis of
former is found in the largest amount in bile. cholesterol, is converted to cholecalciferol (vitamin D3) by
On conjugation with glycine or taurine, conjugated bile ultraviolet rays in the skin.
acids (glycocholic acid, taurocholic acid, etc.) are formed, Q. 3. Phospholipids (structures and functions).
which are more efficient in their function as surfactants. In
the bile, the conjugated bile acids exist as sodium and PHOSPHOLIPIDS
potassium salts, which are known as bile salts. These are complex or compound lipids containing
In the intestine, a portion of primary bile acids undergo phosphoric acid, in addition of fatty acids, nitrogenous base
deconjugation and dehydroxylation to form secondary bile and alcohol. There are two classes of phospholipids:
acids (deoxycholic acid and lithocholic acid). These Glycerophospholipids (or phosphoglycerides) that contain
reactions are catalysed by bacterial enzymes in the glycerol as the alcohol.
intestine. Sphingophospholipids (or sphingomyelins) that contain
SYNTHESIS OF STEROID HORMONES FROM sphingosine as the alcohol.
CHOLESTEROL Glycerophospholipids
Cholesterol is the precursor for the synthesis of all the five Glycerophospholipids are the major lipids that occur in
classes of steroid hormones: 1. Glucocorticoids (e.g. biological membranes. They consist of glycerol 3-
cortisol) phosphate esterified at its C1 and C2 with fatty acids.
Mineralocorticoids (e.g. aldosterone) Usually, C1 contains a saturated fatty acid, while C2
Progestins (e.g. progesterone) 4. Androgens (e.g. contains an unsaturated fatty acid.
testosterone) Phosphatidic acid: This is the simplest phospholipid.
5. Oestrogens (e.g. oestradiol). It does not occur in good concentration in the tissues.
Cholesterol (27C) Basically, phosphatidic acid is an intermediate in the
synthesis of triacylglycerols and phospholipids (Fig. 3.3.4).
Pregnenolone (21C) Lecithins (phosphatidylcholine): These are the most
abundant group of phospholipids in the cell membranes.
O
Progesterone (21C) O CH2—O—C—R1 R2—C—O—CH O
CH2—O—P—O−
O
Aldosterone (21C) Fig. 3.3.4 Phosphatidic acid.
Cortisol (21C) Oestradiol (18C) Chemically, lecithin is a phosphatidic acid with choline as
Fig. 3.3.3 Outline of steroid hormone synthesis from the base (Fig. 3.3.5).
cholesterol. (Note: Numbers in the brackets represent the resultant compound is plasmalogen. Brain and muscle
number of carbon atoms).
contain a good concentration (about 10% of phospho-
O This is an important component of cell membranes. The
O CH2—O—C—R1
CH
action of certain hormones (e.g. oxytocin and vasopressin)
R2—C—O—CH O 3
is mediated through Pi.
O
O CH2—O—C—R
CH2—O—P—O—CH2—CH2—N —CH3 1
R2—C—O—CH
O CholineCH3 O OH OH
CH2—O—P—O
Fig. 3.3.5 Lecithin (phosphatidylcholine). Fig. 3.3.7 Phosphatidyl inositol.
H H
Cephalins (phosphatidylethanolamine): Phosphatidylserine
O− H H OH
Ethanolamine is the nitrogenous base present in (Fig. 3.3.8):
cephalins (Fig. 3.3.6). The amino acid CH H serine is
O myo -inositol
O CH2—O—C—R1 present in this group of
R2—C—O—CH O glycerophospholipids.
CH2—O—P—O—CH2—CH2—N Plasmalogens: When a fatty acid is attached by an ether
O− Ethanolamine linkage at C, of glycerol in the glycerophospholipids, the
Fig. 3.3.6 Cephalin (phosphatidylethanolamine). O
Phosphatidylinositol (Fig. 3.3.7) O CH2—O—C—R1
R2—C—O—CH O
The stereoisomer myo-inositol is attached to phosphatidic CH2—O—P—O—CH2—CH—COO−
acid to give phosphatidylinositol (Pi).

O−NH3+
Serine
Fig. 3.3.8 Phosphatidyl serine.
lipids) of plasmalogens (Fig. 3.3.9).
O CH2—O—CH = CH—R1
R2—C—O—CHO
CH2—O—P—O—CH2—CH2—NH2
O− Ethanolamine
Fig. 3.3.9 Plasmalogen (phosphatidylethanolamine).
Sphingomyelins
Sphingosine is an amino alcohol present in sphingomyelins
(sphingophospholipids). They do not contain glycerol at all.
Sphingosine is attached by an amide linkage to a fatty acid
to produce ceramide. Sphingomyelins are important
constituents of myelin, and are found in good quantity in
brain and nervous tissues.
FUNCTIONS OF PHOSPHOLIPIDS
Phospholipids constitute an important group of compound
lipids that perform a wide variety of functions.
In association with proteins, phospholipids form the
structural components of membranes and regulate
membrane permeability.
Phospholipids (lecithin, cephalin and cardiolipin) in the
mitochondria are responsible for maintaining the
conformation of electron transport chain components and
thus cellular respiration.
Phospholipids are essential for the synthesis of different
lipoproteins and thus participate in the transport of lipids.
Accumulation of fat in liver (fatty liver) can be prevented
by phospholipids; hence they are regarded as lipotropic
factors.
Arachidonic acid, an unsaturated fatty acid, liberated from
phospholipids serves as a precursor for the synthesis of
eicosanoids (prostaglandins, prostacyclins, thromboxanes,
etc.).
Phospholipids (phosphatidylinositol) are involved in signal
transmission across membranes.
Q. 4. Classification of lipids with two examples of
each class.
CLASSIFICATION OF LIPIDS
Lipids are broadly classified into simple, complex, derived
and miscellaneous lipids, which are further subdivided as
follows:
Simple lipids: These are esters of fatty acids with
alcohols. These are mainly of two types: a. Fats and oils
(triacylglycerols)
Waxes.
Complex (or compound) lipids: Esters of
fatty acids with alcohols containing additional groups such
as phosphate, nitrogenous base, carbohydrate, protein, etc.
They are further divided into: a. Phospholipids
Glycerophospholipids: For example lecithin and
cephalin.
Biochemistry 263
Sphingophospholipids: For example sphingomyelins.
Glycolipids: For example cerebrosides and
gangliosides.
Lipoproteins: Macromolecular complexes of lipids with
proteins.
Other complex lipids: Sulpholipids, amino
lipids and lipopolysaccharides are among the other complex
lipids.
Derivedlipids: They include glycerol and other alcohols,
fatty acids, monoacylglycerols and diacylglycerols, lipid-
soluble vitamins, steroid hormones, hydrocarbons and
ketone bodies.
Miscellaneous lipids: These include a large number of
compounds possessing the characteristics of lipids, for
example carotenoids, squalene, hydrocarbons such as
pentacosane (in beeswax), terpenes, etc.
Neutral lipids: The lipids that are uncharged are referred
to as neutral lipids. These are mono-, di-, and
triacylglycerols, cholesterol and cholesteryl esters.
Q. 5. Digestion and absorption of triglycerols.
Hydrolysis: Triacylglycerols undergo stepwise enzymatic
hydrolysis to finally liberate free fatty acids and glycerol.
The process of hydrolysis, catalysed by lipases, is important
for digestion of fat in the gastrointestinal tract and fat
mobilization from the adipose tissues.
Saponification: The hydrolysis of triacylglycerols by alkali
to produce glycerol and soaps is known as saponification.
Triacylglycerol 1 3 NaOH Glycerol 1 3 R-COONa (soaps).
HMG CoA lyase cleaves HMG CoA to produce
acetoacetate and acetyl CoA.
Acetoacetate can undergo spontaneous decarboxylation to
form acetone.
Acetoacetate can be reduced by a dehydrogenase to b-
hydroxybutyrate.
The carbon skeleton of some amino acids (ketogenic) is
degraded to acetoacetate or acyl CoA and, therefore, to
ketone bodies. For example leucine, lysine, phenylalanine,
etc.
Q. 6. Explain the beta-oxidation of fatty acids.
What is the importance of this process?
Refer to the answer of Long Essays Q. 1.
Q. 7. Name the ketone bodies. How are they
formed? Mention two causes of ketosis.
Or
Briefly give the pathway of ketogenesis. How is
the presence of ketone bodies in urine detected?
KETOGENESIS
The synthesis of ketone bodies occurs in the liver. The
enzymes for ketone body synthesis are located in the
mitochondria matrix. Acetyl CoA, formed by oxidation of
262 Quick Review Series: BDS 1st Year
fatty acids, pyruvate or some amino acids are the precursors
for ketone bodies. Ketogenesis occurs through the
following reactions (Fig. 3.3.10):
Two moles of acetyl CoA condense to form acetoacetyl
CoA. This reaction is catalysed by thiolase.
Acetoacetyl CoA combines with another molecule of acetyl
CoA to produce b-hydroxy b-methylglutaryl CoA (HMG
CoA). HMG CoA synthase, catalysing this reaction,
regulates the synthesis of ketone bodies.
Acetyl CoA Acetyl CoA
CoA-SH β-Ketothiolase
Acetoacetyl CoA
Acetyl CoA
HMG CoA synthase
CoA.SH
3-Hydroxy-β-methylglutaryl CoA (HMG CoA
) affect glucose, amino acid and fat metabolism in a manner
Acetyl CoA HMG CoA lyase
Acetoacetate
Spontaneous
β-Hydroxybutyrate
CO2 dehydrogenase
NADH + H +
NAD+
Acetone β-Hydroxybutyrate
Fig. 3.3.10 Synthesis of ketone bodies (ketogenesis).
The ketosis is most commonly associated with starvation
and severe uncontrolled diabetes mellitus. The presence of
ketone bodies in urine is detected by Rothera’s test.
SHORT NOTES
Q. 1. Fatty liver.
The normal concentration of lipid (mostly phospholipid) in
liver is around 5%. Liver is not a storage organ for fat,
unlike adipose tissue. However, in certain conditions, lipids
— especially the triacylglycerols — accumulate
excessively in liver, resulting in fatty liver.
Fatty liver may occur due to two main causes:
Increased synthesis of triacylglycerols
Impairment in lipoprotein synthesis. Q. 2. Cholesterol.
Cholesterol literally means solid alcohol from bile.
Cholesterol is exclusively found in animals and is the most
abundant animal sterol.
It is widely distributed in all cells and is a major component
of cell, membranes and lipoproteins. Cholesterol (Greek:
chole, meaning bile) was first isolated from bile.
FUNCTIONS OF CHOLESTEROL
Cholesterol functions as an insulating cover for the
transmission of electrical impulses in the nervous tissue.
Cholesterol performs several other biochemical functions,
which include its role in membrane structure and function,
in the synthesis of bile acids, hormones (sex and cortical)
and vitamin D.
Q. 3. Derivatives of cholesterol and their
importance.
Cholesterol (50%) serves as a precursor for the synthesis of
steroid hormones, vitamin D, coprostanol and cholestanol.
It is the precursor for the synthesis of all the five classes of
steroid hormones:
Glucocorticoids (e.g. cortisol)
Mineralocorticoids (e.g. aldosterone)
Progestins (e.g. progesterone)
Androgens (e.g. testosterone)
Oestrogens (e.g. oestradiol).
Glucocorticoids (e.g. cortisol, cortisone and corticosterone)
that is opposite to the action of insulin.
They promote the synthesis of glucose (gluconeogenesis),
increase the circulating free fatty acids, and they exhibit
catabolic and anabolic effects on protein and nucleic acid
metabolism.
Mineralocorticoids regulate water and electrolyte balance,
and androgens and oestrogens affect sexual development
and functions.
Q. 4. What are essential fatty acids? Name them.
The fatty acids that cannot be synthesized by the body, and,
therefore, should be supplied in the diet are known as
essential fatty acids.
Chemically, they are polyunsaturated fatty acids, namely,
linoleic acid, linolenic acid and arachidonic acid. Q. 5.
Ketone bodies.
Or
Name ketone bodies and two conditions in which
they are excreted.
The compounds, namely, acetone, acetoacetate, and b-
hydroxybutyrate (or 3-hydroxybutyrate) are known as
ketone bodies.
Only the first two are true ketones, while -hydroxybutyrate
does not possess a keto (C5O) group. Ketone bodies are
water soluble and energy yielding.
They are excreted in the following conditions:
Starvation
Severe uncontrolled diabetes mellitus.
Q. 6. What is ketosis? List two causes of ketosis.
 Biochemistry 263

Lipids are important as cellular metabolic regulators

When the rate of synthesis of ketone bodies exceeds the rate
of utilization, their concentration in blood increases; this is
known as ketonaemia.
This is followed by ketonuria—excretion of ketone bodies
in urine. The overall picture of ketonaemia and ketonuria is
commonly referred to as ketosis.
Ketosis is most commonly associated with starvation and
severe uncontrolled diabetes mellitus. Q. 7. Beta-
oxidation.
The fatty acids in the body are mostly oxidized by b-
oxidation. b-Oxidation may be defined as the oxidation of
fatty acids on the b-carbon atom. This results in the
sequential removal of a two-carbon fragment, acetyl CoA.
Q. 8. Fat metabolism.
The metabolism of lipids or fats, comprises the metabolism
of neutral fats or triglycerides, phospholipids, sterols and
others. Q. 9. Unsaturated fatty acids.
(steroid hormones and prostaglandins).
Q. 13. In which form are fats stored in our body?
Where is fat stored?
Fats as stored fuel: Triacylglycerols are the
most abundant group of lipids that primarily function as
fuel reserves of animals.
The fat reserve of normal humans (men 20%, women 25%
by weight) is sufficient to meet the body caloric
requirements for 2–3 months.
In the body they are present in the cytoplasm as well as the
cell wall, and are also in specialized areas in the body as
depots of fat in which form energy is stored.
Nervous tissues are particularly rich in lipids. The
subcutaneous fat serves the role of insulating against
atmospheric heat and cold, and also helps in rounding off
the contours of the body.
Q. 14. What are lecithins? Mention their
physiological importance.

Unsaturated fatty acids contain one or more double bonds. Lecithins (phosphatidylcholine): These are the
Both saturated and unsaturated fatty acids almost equally most abundant group of phospholipids in the cell
occur in the natural lipids. membranes. Chemically, lecithin is a phosphatidic acid
Fatty acids with one double bond are known as with choline as the base.
monounsaturated and those with two or more double bonds Dipalmitoyl lecithin is an important phosphatidylcholine
are collectively known as polyunsaturated fatty acids. found in lungs. It is a surface-active agent and prevents the
Q. 10. Phenylketonuria. adherence of inner surface of the lungs due to surface
tension.
Phenylketonuria is the most common metabolic disorder in
amino acid metabolism. The incidence of phenylketonuria
is 1 in 10,000 births.
It is due to the deficiency of the hepatic enzyme—
phenylalanine hydroxylase—caused by an autosomal
recessive gene.
Q. 11. Normal values of cholesterol.

Normal values of cholesterol are as follows:

Cholesterol, total 150–225 mg/dL
HDL fraction 30–60 mg/dL
LDL fraction 80–150 mg/dL
VLDL fraction 20–40 mg/dL
Q. 12. Name any four functions of lipids.

Lipids perform several important functions:

They are the concentrated fuel reserve of the body
(triacylglycerols).
Lipids are the constituents of membrane structure and
regulate the membrane permeability (phospholipids and
cholesterol).
They serve as a source of fat-soluble vitamins (A, D, E and
K).
262 Quick Review Series: BDS 1st Year
Lysolecithin is formed by removal of the fatty acid either at
C1 or C2 of lecithin.
1–1.5 kg. Around 99% of it is present in the bones and
teeth. A small fraction (1%) of the calcium is found outside
Topic 4 METABOLISM
SUBSTANCES
LONG ESSAYS
Q. 1. What is the normal serum calcium level? How
is it regulated? Enumerate the physiological func- Discuss the functions of calcium in human body
of calcium.
and explain the homeostasis of blood calcium.
Or
What is the normal blood calcium level? What are The most abundant among minerals in the body is calcium. the
factors that maintain this level? The total content of calcium in an adult man is around
the skeletal tissue. Normal blood (serum) calcium level is
9–11 mg/100 mL or 5 mEq/L.
Calcium exists in the plasma in three fractions: ionized or
diffusible calcium, protein bound or nondiffusible and
complexed (citrate and phosphate).
About 5 mg/dL of calcium is in ionized form and is
metabolically active, and about 1 mg/dL is complexed with
phosphate. Bicarbonate and citrate are the two forms which
are diffusible from blood to tissues, whereas protein-bound
calcium — 4 mg/dL is bound to blood proteins — is not
diffusible. Biochemical functions of calcium are as follows:
Formation and development of bones
and teeth: Calcium, along with phosphate, is
essential for the formation, and physical strength of bones
and teeth. Bones which are in a dynamic state serve as
reservoir of Ca. Osteoblasts induce the bone formation
while osteoclasts result in demineralization.
Contraction of muscle: Ca21 triggers muscle
contraction by interacting with troponin C. Calcium also
activates ATPase and increases the interaction between
actin and myosin, facilitating excitation–contraction
coupling. Blood coagulation: Calcium is also known as
factor IV. Ionized calcium is required in blood coagulation
process and several reactions in the cascade of blood
clotting process are dependent on Ca21 (factor IV).
Nerve conduction: Ca21 is necessary for the transmission
of nerve impulse.
Membrane integrity and permeability:
Ca21 influences the membrane structure and transport of
water and several ions across it. Calcium regulates
permeability of membranes.
Activation of enzymes: Ca21 is needed for the
direct activation of several enzymes, e.g. lipase
(pancreatic), ATPase and succinate dehydrogenase, and
certain proteolytic enzymes.
Calmodulin-mediated action of Ca21:
Calmodulin (molecular weight 17,000 Da) is a calcium-
binding regulatory protein. Calcium–calmodulin complex
activates certain enzymes, e.g. adenyl cyclase,
OF INORGANIC
Or
tions
phospholipase C, Ca21-dependent protein kinases like
pyruvate kinase or phosphorylase kinase, etc.
Intracellular messenger: Certain hormones exert their
action through the mediation of Ca 21 instead of cAMP.
Calcium is regarded as a second messenger for such
hormonal action, e.g. epinephrine in liver glycogenolysis.
Calcium serves as a third messenger for some hormones;
e.g. antidiuretic hormone acts through cAMP and then
through Ca21.
Release of hormones: Ca21 facilitates the release of
certain hormones like insulin, parathyroid hormone,
calcitonin from the endocrine glands.
PLASMA CALCIUM
Virtually there is no calcium in erythrocytes. Most of the
blood calcium is present in the plasma itself. The normal
concentration of plasma or serum Ca is 9–11 mg/dL (4.5–
5.5 mEq/L). About half of this (5 mg/dL) is in the ionized
form, which is functionally the most active. At least 1
mg/dL of serum Ca is found in association with citrate or
phosphate. The other half of serum Ca (4–5 mg/dL) is
bound to proteins, mostly albumin and, to a lesser extent,
globulin. Ionized and citrate- (or phosphate-) bound Ca is
diffusible from blood to the tissues while protein bound Ca
is nondiffusible.
Factors regulating plasma calcium levels are as follows:
PTH (parathyroid hormone)
Vitamin D or calcitriol
Calcitonin
Plasma proteins 5. Plasma phosphate.
Calcium is almost exclusively present in blood plasma or
serum. The hormones calcitriol, PTH and calcitonin are the
major factors that maintain homeostasis of the plasma
calcium within a range 9–11 mg/dL (Fig. 3.4.1).
Parathyroid hormone

PTH is secreted by parathyroid glands. Under the negative
feedback regulation of serum Ca 21, PTH is released from
parathyroid glands. In fasting state, there is no absorption
from intestine; the normal plasma concentration of calcium
is maintained primarily by the action of PTH on
mobilization of calcium from bones (Fig. 3.4.1).
Intestine Ca PTH
Calcitriol Vitamin D
Calcitonin
calcitriol Plasma Ca
Bone Ca 9−11 mg/dL Renal tubular Ca
PTH PTH
Fig. 3.4.1 Homeostasis of blood calcium.
Mechanism of action of PTH
PTH has three major independent sites of action: bone,
kidney and intestine. PTH binds to a membrane receptor
protein on the surface of target cell and activates adenylate
cyclase to liberate cAMP which, in turn, increases
intracellular calcium that promotes the phosphorylation of
proteins and finally brings about the biological actions. The
prime function of PTH is to elevate serum calcium level.
Action on the bone: PTH causes
decalcification or demineralization of bone, a process
carried out by osteoclasts. PTHstimulated increased activity
of the enzymes pyrophosphatase and collagenase results in
bone resorption. Demineralization ultimately leads to an
increase in the blood Ca level. The action of PTH on bone
is quantitatively very significant to maintain Ca
homeostasis, which is being done at the expense of loss of
Ca from bone, particularly in dietary Ca deficiency.
Action on the kidney: PTH increases the Ca
reabsorption or decreases renal excretion of Ca 1, resulting
in rapid action of PTH to elevate blood Ca levels. PTH
promotes the production of calcitriol or 1,25-dihydroxy-
cholecalciferol (1,25 DHCC) in the kidney by stimulating
1-hydroxylation of 25-hydroxycholecalciferol.
Action on the intestine: PTH has the
indirect action on the intestine. It increases the intestinal
absorption of Ca1 by promoting the synthesis of calcitriol.
Calcitriol
Calcitriol is nothing but physiologically active form of
vitamin D and is a hormone. Calcitriol induces a specific
calcium-binding protein in the intestinal mucosal cells,
which increases the intestinal absorption of calcium as well
as phosphate. Thus, blood Ca level is increased by
calcitriol. By acting independently on the bone, vitamin D
increases the number and activity of osteoblasts, and
stimulates calcium uptake by osteoblasts and promotes
calcification or mineralization and remodelling of bone.
Calcitonin
SHORT ESSAYS
Biochemistry 263
Calcitonin was reported in 1962 by Hirsch. It is secreted by
parafollicular cells of thyroid gland. The action of
calcitonin on calcium metabolism is antagonistic to that of
PTH. Thus, by increasing the activity of osteoblasts,
calcitonin promotes calcification. Further, calcitonin
decreases bone resorption and increases the excretion of Ca
into urine.
Q. 2. Write the dietary sources, factors influencing
absorption, biochemical functions and daily
requirements of calcium.
DIETARY REQUIREMENTS OF CALCIUM
Adult males and females:800 mg/day
Women during pregnancy, lactation 1.5 g/day and
postmenopause:
Children (1–18 years): 0.8–1.2 g/day
Infants (,1 year): 300–500 mg/day DIETARY SOURCES
Best sources: Milk and milk products, especially cow milk.
Good sources: Beans, leafy vegetables, fish, cabbage, egg
yolk.
ABSORPTION
The absorption of calcium mostly occurs in the first and
second parts of duodenum by an energy-dependent active
process. It is influenced by several factors.
Factors influencing absorption
Factors promoting Ca absorption
Vitamin D through its active form, calcitriol, induces the
synthesis of calcium-binding protein in the intestinal
epithelial cells and promotes Ca absorption.
Parathyroid hormone enhances Ca absorption through the
increased synthesis of calcitriol.
An acidic or low pH of intestine is more favourable for Ca
absorption.
Lactose promotes calcium uptake by intestinal cells.
The amino acids lysine and arginine facilitate increased Ca
absorption.
A high-protein diet favours its absorption.
Factors inhibiting Ca absorption
Phytates present in cereals and oxalates present in the
vegetables like cabbage and spinach form insoluble salts,
and interfere with Ca absorption.
High content of dietary phosphate prevents Ca uptake. The
dietary ratio of Ca and P—between 1:2 and 2:1—is ideal
for optimum Ca absorption by intestinal cells.
The free fatty acids react with Ca to form insoluble calcium
soaps. This is particularly observed when the fat absorption
is impaired as in sprue syndrome.
Alkaline condition (high pH) is unfavourable for Ca
absorption.
High content of dietary fibre interferes with Ca absorption.
For biochemical functions of calcium, refer to the answer of
Long Essays Q. 1.
262 Quick Review Series: BDS 1st Year

Q. 1. Functions of calcium.
Calcium is the most abundant among minerals in the
body. The total content of calcium in an adult man is about 1–1.5 kg. As much as 99% of it is present in the Q.
2. Regulation of serum calcium.
bones and teeth. A small fraction (1%) of the calcium is
found outside the skeletal tissue, which performs a wide variety of functions. For functions of calcium, refer to Factors
regulating plasma calcium levels are discussed in answer of Long Essays, Q. 1. Long Essays Q. 1.
SHORT NOTES
Q. 1. Importance of iodine. It is essential for normal growth, reproduction and longevity
Iodine is mainly required for the synthesis of thyroid of animals.
hormones, namely, thyroxin (T4) and triiodothyronine (T3), Q. 6. Potassium balance.
which are involved in several biochemical functions.
Our body contains about 50 mg iodine and most of it (80%) This is the principal action of the intracellular fluid. About
is present in the thyroid gland. Muscle, salivary glands, and 4 g potassium is present in normal diets. Its deficiency is
ovaries also contain some amount of iodine. Daily rare. Whole blood contains 200 mg/100 mL, but plasma
requirement as recommended by the National Research contains only 20 mg/100 mL (5 mEq/L). It is present in all
Council (USA) is liberal intake of 100–200 µg. tissues.
Sea water has highest iodine content. Seafood, fruits, Loss of potassium from tissues occurs in wasting diseases
vegetables, cereals and meat are good sources of iodine. Q. and in severe dehydration. In severe diarrhoea and vomiting
2. Normal value of serum calcium. also, potassium may be lost in large amounts. Certain
The normal concentration of plasma or serum Ca is 9–11 diuretics (e.g. acetazolamide or diamox) also increase its
mg/dL (4.5–5.5 mEq/L). urinary excretion. Tissue protein synthesis causes an uptake
Q. 3. Four functions of calcium. Or Functions of of potassium, about 2 mg per each gram of protein, and
calcium in the body. synthesis of glycogen in liver and muscle will take up about
The calcium is required for regulating a large number of 3–4 mg of potassium for each gram of glycogen.
cellular activities, nerve and muscle function, hormonal Q. 7. Describe the functions and deficiency of
action, blood coagulation and cell motility. fluorine.
Calcium, along with phosphate, is required for the Or
formation (of hydroxyapatite) and physical strength of Functions of fluoride.
skeletal tissue. Bones which are in a dynamic state serve as Or
reservoir of calcium. Q. 4. Name the hormones that Role of fluoride in prevention of dental caries.
regulate serum calcium level.
The hormones which regulate serum calcium levels are Fluoride is necessary for normal development of teeth and
calcitriol, parathyroid hormone and calcitonin. bones. It is protective against dental caries. It forms a
Q. 5. Name two trace elements and their biological protective layer of acid-resistant fluoroapatite with
role. hydroxyapatite of the enamel and prevents the tooth decay
by bacterial acids. Further, fluoride inhibits the bacterial
Trace elements are as follows: enzymes and reduces the production of acids.
Essential trace elements: Iron, copper, iodine, zinc, Deficiency of fluoride: Drinking water
manganese, fluorine, selenium and chromium. containing less than 0.5 ppm of fluoride is associated with
Possibly essential trace elements: Nickel, vanadium, the development of dental caries in children.
cadmium and barium. Q. 8. Dental fluorosis.
Non-essential trace elements: Aluminium, mercury and
silver. Excessive intake of fluoride is harmful to the body. Intake
BIOLOGICAL ROLE OF IRON of fluoride more than 2 ppm (particularly . 5 ppm) in
As a component of haemoglobin, myoglobin and children causes mottling of enamel and discolouration of
cytochromes, iron plays a key role in oxygen transport and teeth. The teeth are weak and become rough with
cellular oxidation. characteristic brown or yellow patches on their surface.
Iron is important in maintaining effective These manifestations are collectively referred to as dental
immunocompetence of the body. fluorosis.
BIOLOGICAL ROLE OF ZINC Q. 9. Fluorosis.
It is necessary to maintain the normal levels of vitamin A in
the serum. Intake of fluoride is harmful to the body. An intake above 2
ppm (particularly .5 ppm) in children causes mottling of
 Biochemistry 263

enamel and discolouration of teeth. The teeth are weak and
become rough with characteristic brown or yellow patches
on their surface. These manifestations are collectively
referred to as dental fluorosis.
An intake of fluoride above 20 ppm is toxic and causes
pathological changes in the bones. Characteristic feature of
skeletal fluorosis is hypercalcification — increasing the
Q. 1. Write briefly about electron transport chain.
The electrons in mitochondria participate in sequential
oxidation–reduction of various redox centres in enzyme
complexes of mitochondria. The electrons are transferred
from higher potential to lower potential. This flow of
electrons occurring through successive dehydrogenase
enzymes together is known as electron transport chain
(ETC). It is located in inner membrane of mitochondria.
The energy-rich carbohydrates, fatty acids and amino acids
finally get oxidized to CO2 and H2O after undergoing
through a series of metabolic reactions. ETC represents the
density of the bones of limbs, pelvis and spine. Even the
ligaments of spine and collagen of bones get calcified.
Neurological disturbances are also commonly observed.
The manifestations described constitute skeletal fluorosis.
In the advanced stages, the individuals are crippled and
cannot perform their daily routine work due to stiff joints.
This condition of advanced fluorosis is referred to as genu
valgum.
to produce NADH and FADH2, respectively. These two
reduced coenzymes pass through the ETC or respiratory
chain and, finally, reduce oxygen to water. The passage of
electrons through the ETC is associated with the loss of free
energy. A part of this free energy is utilized to generate
ATP from ADP and Pi.
ETC is organized into five distinct complexes as follows
(Fig. 3.5.2):
Complex I: NADH–CoQ reductase or NADH–
dehydrogenase complex
Complex II: Succinate-Q-reductase
Complex III: Cytochrome reductase 4. Complex IV:

Topic 5 BIOLOGICAL OXIDATION

SHORT ESSAY
final stage of oxidizing the reducing equivalents derived Cytochrome oxidase
from various metabolic intermediates to water (Fig. 3.5.1). 5. Complex V: ATP synthase.
The reducing equivalents from various metabolic
intermediates are transferred to coenzymes NAD 1 and FAD
Carbohydrates
amino acids and Carbon dioxide + Water
fatty acids 4O2
NAN+ ADP + Pi
FAD
ETC
ATP
NADH + H+
H2O
FADH2

Fig. 3.5.1 Summary of biological oxidation.

The complexes I, II, III and IV are electron carriers, whereas complex V is responsible for ATP production.
There are five distinct carriers that are sequentially arranged in the ETC, as shown in Fig. 3.5.2, which are responsible for
the transfer of electrons from a given substrate to ultimately combine with proton and oxygen to form water.
NICOTINAMIDE NUCLEOTIDES
Among the two coenzymes NAD1 and NADP1 of vitamin niacin, NAD1 is more actively involved in the ETC. NAD1 is

Fig. 3.5.2 Electron transport chain.

reduced to NADH 1 H1 by dehydrogenases with the
removal of two hydrogen atoms from the substrate. The
substrates include glyceraldehyde-3-phosphate, pyruvate,
isocitrate, a-ketoglutarate, and malate.
FLAVOPROTEINS
The enzyme NADH dehydrogenase is a flavoprotein with
FMN as the prosthetic group. The coenzyme FMN receives
two electrons and a proton to form FMNH 2. NADH
dehydrogenase is a complex enzyme closely associated
with nonheme iron proteins or iron–sulphur (FeS) proteins.
262 Quick Review Series: BDS 1st Year

NADH 1 H1 1 FMN n NAD1 1 FMNH2
IRON–SULPHUR PROTEINS
The mechanism of action of iron–sulphur proteins in the
ETC is not specific.
COENZYME Q
Coenzyme Q or ubiquinone is a quinone derivative with a
variable isoprenoid side chain. The mammalian tissues
possess a quinone with 10 isoprenoid units, which are
known as coenzyme Q10 (CoQ10).
The Q-cycle facilitates switching from ubiquinol, a two
electron carrier, to cytochrome c, a single electron carrier.
CYTOCHROMES
Cytochrome c is a small conjugated protein containing 104
amino acids and a heme group. It is a central member of the
ETC with an intermediate redox potential. The iron of heme
in cytochromes is alternately oxidized (Fe31) and reduced
(Fe21), which is essential for the transport of electrons in the
ETC.
Q. 1. Explain the role of kidney in acid–base
balance.
The electrons are transported from coenzyme Q to
cytochromes b, c, c, a and a3 in an orderly manner.
The property of reversible oxidation–reduction of heme iron
present in cytochromes allows them to function as effective
carriers of electrons in ETC. In the final stage of ETC, the
transported electrons, the free protons and the molecular
oxygen combine to produce water.
Free energy is utilized to generate ATP from ADP and Pi at
the following three sites:
Oxidation of FMNH2 by CoQ
Oxidation of cytochrome b by cytochrome c1
Cytochrome oxidase reaction.
The respiratory chain or ETC can be blocked by sitespecific
inhibitors like rotenone, amytal piericidin, piericidin A,
antimycin A, 2,3-dimercaptopropanol (BAL), sodium azide,
cyanide and carbon monoxide, etc.
to the alkali reserve of the body. The H 1 is excreted in urine
after it combines with a non-carbonate base (Fig. 3.6.1).

The kidneys have a highly significant role in the

maintenance of acid–base balance or pH of extracellular
fluid in the body. These regulate the blood pH by

Topic 6 WATER, ELECTROLYTE AND ACID–

BASE BALANCE
SHORT ESSAYS
maintaining the alkali reserve and excretion or reabsorption
of the acidic or basic substances, as required. The enzyme
carbonic anhydrase has a key role in the renal regulation of
pH. Blood Tubular lumen
Renal
The major renal mechanisms for the regulation of pH are as tubular
follows: cell
Excretion of H1 ions
Na+ Na+ Na+
Reabsorption of bicarbonate
Excretion of titratable acid (net acid excretion) 4. Excretion
of ammonium ions. HCO¯
3 HCO¯
3 + H
+
H+

Excretion of H1 ions: The only route Alkali Hydrogen ions

1 recovered to
through which the H ions can be eliminated from the body
is kidney. The excretion of H1 ions occurs in the proximal
convoluted tubules of the nephrons and is associated with
the regeneration of HCO3–, as shown in Fig. 3.6.1. In the
renal tubular cell, carbonic anhydrase catalyses the
production of H2CO3 from CO2 and H2O. H2CO3 then
dissociates to H1 and HCO3–. In exchange for Na1, the H1
ions are secreted into the tubular lumen. Both Na 1 and
HCO3– are reabsorbed into the blood. This is an effective
mechanism to eliminate acids (H1) from the body with a
simultaneous generation of HCO3–. The bicarbonate adds up
H2CO3 excreted
plasma CA
CO2+ H2O
Fig. 3.6.1 Excretion of H1 ions in renal regulation of blood pH.
Reabsorption of bicarbonate: This is primarily
a mechanism responsible to conserve the blood HCO 3– by
preventing loss of HCO3– through urine. The normal urine
is almost free from HCO3– as it is completely reabsorbed by
proximal convoluted tubules. In this mechanism, there is no
generation of new bicarbonate or net excretion of H 1. The
net effect of this process is reabsorption of filtered
bicarbonate by sodium–hydrogen exchanger (Fig. 3.6.2).
 Biochemistry 263

Excretion of titratable acid: resists the change in pH by the addition of acid or alkali. It
Titratable acidity is a measure of net acid excreted cannot remove H1 ions from the body but temporarily acts
by the kidney. The term titratable acidity of urine means as a shock absorbent to reduce the free H 1 ions. Buffers can
number of millilitres of N/10 NaOH required to titrate 1 mL respond quickly in addition to acid or base; but they do not
of urine to pH 7.4. serve to eliminate the acid from the body and are also
unable to replenish the body alkali reserve.
Blood Tubular lumen
Renal For final elimination of acids, the respiratory and renal
NaHCO3 (filtered
tubular
by glomerulus)
regulations are highly essential.
cell RESPIRATORY MECHANISM
Na+ Na+ Na+
Respiratory system provides a mechanism for rapid
HCO¯
3 adjustment of acid–base balance by regulating the
HCO¯
3 HCO¯
3 + H
+
H+
concentration of carbonic acid in the blood.
Carbonic anhydrase
Alkali Hydrogen ions
H2CO3 H2CO3 H2CO3 ↔ CO2 + H2O
recovered excreted
to plasma CA CA A respiratory centre, located in the medulla of the brain,
CO2 + H2O
controls the rate of respiration or the rate of removal of
CO2 + H2O
CO2. This centre is highly sensitive to changes in the pH of
Fig. 3.6.2 Reabsorption of bicarbonate from renal tubule. blood. When there is decrease in blood pH it results in
The excreted H1 ions are actually buffered in the urine by hyperventilation to blow off CO2, thereby reducing the
phosphate buffer. The acidic–basic phosphate pair is H2CO3 concentration. Simultaneously, the H1 ions are
considered as urinary buffer. eliminated as H2O.
Excretion of ammonium ions: This is Since hyperventilation cannot proceed for long, respiratory
one of the mechanisms to buffer H 1 ions secreted into the control of blood pH is immediate but only a short-term
tubular fluid. The H1 ion combines with NH3 to form regulatory process.
ammonium ion (NH41), which is primarily excreted through RENAL MECHANISM FOR PH REGULATION
distal convoluted tubule. The enzyme glutaminase catalyses The kidneys have a highly significant role in the
deamidation of glutamine to glutamate and NH3. The NH3, maintenance of acid–base balance or pH of extracellular
liberated in this reaction, diffuses into the tubular lumen fluid in the body. The kidneys regulate the blood pH by
where it combines with H1 to form NH41 ions, which cannot maintaining the alkali reserve and excretion or reabsorption
diffuse back into tubular cells and, therefore, are excreted of the acidic or basic substances, as situation demands. The
into urine. enzyme carbonic anhydrase has a key role in the renal
NH41 is a major urine acid, about half to two-thirds of body regulation of pH.
acid load is eliminated in the form of NH41 ions. The major renal mechanisms for the regulation of pH are as
Q. 2. What is the normal pH of the blood? Explain follows: 1. Excretion of H1 ions
various mechanisms by which it is regulated. Reabsorption of bicarbonate
Excretion of titratable acid (net acid excretion) 4. Excretion
Normal pH of blood plasma is maintained within a narrow of ammonium ions.
range of 7.38–7.42. If the pH is below 7.38 the condition is Excretion of H1 ions: Kidney is the
called acidosis, and if it is above 7.42 it is known as only route through which the H 1 can be eliminated from the
alkalosis. body. This is an effective mechanism to eliminate acids
In the body, three lines of defences have been developed to (H1) from the body with a simultaneous generation of
regulate the body’s acid–base balance and maintain the HCO3–. The latter adds up to the alkali reserve of the body.
blood pH (around 7.4): The H1 combines with a non-carbonate base and is excreted
Blood buffers (first line of defence) in urine.
Respiratory mechanism (second line of defence) III. Renal Reabsorption of bicarbonate: This mechanism
mechanism for pH regulation (third line of defence). is primarily responsible to conserve the blood HCO 3–. The
BLOOD BUFFERS normal urine is almost free from HCO3–.
The blood contains three buffer systems: Excretion of titratable acid:
1. Bicarbonate buffer 2. Phosphate buffer Titratable acidity is a measure of acid excreted into
3. Protein buffer. urine by the kidney. Titratable acidity reflects the H 1 ions
A buffer may be defined as a solution of a weak acid and its excreted into urine, which are actually buffered in the urine
salt with a strong base. The buffering capacity is dependent by phosphate buffer.
on the absolute concentration of salt and acid. The buffer
262 Quick Review Series: BDS 1st Year
Excretion of ammonium ions: This is
one of the mechanisms to buffer H 1 ions secreted into the
tubular fluid. The H1 ion combines with NH3 to form
ammonium ion (NH41), which is primarily excreted through
distal convoluted tubule. The enzyme glutaminase catalyses
deamidation of glutamine to glutamate and NH3. The NH3,
Q. 1. Importance of buffers in blood.
A buffer may be defined as a solution of a weak acid and its
salt with a strong base.
The blood contains following three buffer systems:
1. Bicarbonate buffer system 2. Phosphate buffer system
3. Protein buffer system.
The buffer resists the change in pH by the addition of acid
SHORT NOTE
or alkali, and the buffering capacity depends upon the
absolute concentration of salt and acid. The buffer cannot
remove H1 ions from the body but temporarily acts as a
shock absorbent to reduce the free H 1 ions. The H1 ions
have to be ultimately eliminated by the renal mechanism.
Enzymes are broadly categorized as follows:
Intracellular enzymes: Enzymes are functional
within cells where they are synthesized.
Extracellular enzymes: Enzymes are functional
outside the cell where they are synthesized, e.g. all the
digestive enzymes.
According to the IUB (International Union of
Topic 7 ENZYMES
LONG ESSAY
Q. 1. Define an enzyme. How are enzymes classi-
Enzymes can be defined as soluble, colloidal, biocatalysts
Describe the factors affecting enzyme-
which are synthesized by living cells, but are capable of
acting independently of the cells and are specific in their
action.
Biochemistry) system (1964), enzymes are divided into six
major classes based on their function.
Oxidoreductases: Enzymes catalysing oxidation–
reduction reactions, e.g. lactate dehydrogenase (LDH;
NAD), succinate dehydrogenase (FAD).
ing water, e.g. aldolase.
Isomerases: Enzymes involved in all the isomerization
reactions, e.g. triose phosphate isomerase.
Ligases: Enzymes catalysing the synthetic reactions of
linking together of two compounds, e.g. glutamine
synthetase.
Each class on its own represents the general type of reaction
brought about by the enzymes of that class. Each class in
turn is subdivided into many subclasses, which are further
divided. International Union of Biochemistry and
liberated in this reaction, diffuses into the tubular lumen
where it combines with H1 to form NH41 ions, which cannot
diffuse back into tubular cells and, therefore, are excreted
into urine. NH41 is a major urine acid, about half to two-
thirds of body acid load is eliminated in the form of NH 41
ions.
Transferases: Enzymes that catalyse the transfer of
functional groups other than hydrogen from one substrate to
another, e.g. hexokinase.
Hydrolases: Enzymes that bring about hydrolysis of
compounds and then breaking the bond, e.g. acetyl choline
esterase.
Lyases: Enzymes specialized in the addition or removal of
water, ammonia, CO2, etc. cleave bonds without add-
Velocity
O
Concentration
Fig. 3.7.1 Effect of enzyme concentration on enzyme velocity.
2. Concentration of substrate: With an
increase in the concentration of substrate, the velocity of
fied?
catalysed reactions.
enzyme reaction gradually increases within the limited
range of substrate levels. When velocity is plotted against
the substrate concentration, a rectangular hyperbola is
obtained. The graph shows three distinct phases of the
reaction (Fig. 3.7.2).
Molecular Biology (IUBMB) suggested a system of
nomenclature of enzymes. A four-digit Enzyme
Commission (EC) number is assigned to each enzyme
representing the class (first digit), subclass (second digit),
sub-subclass (third digit) and the individual enzyme (fourth
digit); e.g. enzyme code for alcohol dehydrogenase is
1.1.1.1, which means it is first enzyme of sub-subclass 1 of
subclass 1 of the class 1.
FACTORS AFFECTING ENZYME ACTIVITY
 Biochemistry 263

The various factors that influence the enzyme activity are as complex. A low Km value indicates a strong affinity
follows: between enzyme and substrate, whereas a high K m value
Concentration of enzyme reflects a weak affinity between them.
Concentration of substrate Effect of temperature: Velocity of an enzyme
Effect of temperature reaction increases with increase in temperature up to a
Effect of pH maximum and then declines. A bell-shaped curve is usually
Effect of product concentration observed (Fig. 3.7.3).
Effect of activators or inhibitor.
1. Concentration of enzyme: Concentration
of the enzyme and the velocity of the reaction are directly
proportionate to each other. As the concentration of the

Enzyme velocity
enzyme increases, the velocity of the reaction
proportionately increases (Fig. 3.7.1). In fact, this property
of enzyme is useful in determining the serum enzymes for
the diagnosis of diseases.

C
Vmax
Velocity

Optimum
B

½ Vmax
0 10 20 30 40 50 60 70 80
A Km Temperature (°C)
Fig. 3.7.3 Effect of temperature on enzyme velocity.
Concentration of substrate For most of the enzymes, the optimum temperature is 40–
Fig. 3.7.2 Effect of substrate concentration on enzyme velocity. 45°C. However, a few enzymes, e.g. venom
Enzyme kinetics and Km value: The enzyme (E) and phosphokinases, muscle adenylate kinase are active even at
substrate (S) combine with each other to form an unstable 100°C. Majority of the enzymes become inactive at higher
enzyme–substrate complex (ES) for the further formation of temperature above 70°C. In general, when the enzymes are
product (P). exposed to a temperature above 50°C, denaturation leading
k to derangement in the native structure of the protein and
k1
3
active site is seen.
E + S k2 ES E+P Effect of pH: The enzyme activity is
Here k1, k2, and k3 represent the velocity constants for the considerably influenced by increase in the hydrogen ion
respective reactions; Km, the Michaelis–Menten constant (or concentration (pH).
Brig’s and Haldane’s constant), is given by the following
formula:
k2 + k3 km k1 O
p
Enzyme velocity

The following equation is obtained after suitable algebraic t

manipulation: i
m
Vmax [S] u
m
V = km [s]
where V is measured velocity
Vmax is maximum velocity
Km is Michaelis–Menten constant
S is substrate concentration
Km or the Michaelis–Menten constant is defined as the pH
concentration of substrate to produce half-maximum Fig. 3.7.4 Effect of pH on enzyme velocity.
velocity in an enzyme-catalysed reaction. It indicates that Each enzyme has an optimum pH at which the velocity is
when the substrate concentration equals the K m value, half maximum. A bell-shaped curve is normally obtained for pH
of the enzyme molecules, i.e. 50%, are bound with the versus enzyme velocity graph (Fig. 3.7.4). Around neutral
substrate molecules. pH in the range of 6–8, most of the enzymes of higher
Km value is a constant and characteristic feature of a given organisms show optimum activity.
enzyme. It is important for measuring the strength of ES
262 Quick Review Series: BDS 1st Year
Effect of productconcentration: The enzyme
velocity decreases by the accumulation of reaction
products. For certain enzymes, the products combine with
the active site of enzyme and form a loose complex, which
inhibits the enzyme activity. This type of inhibition is
generally prevented by a quick removal of products formed
in the living systems.
Effect of activators: The inorganic metallic
cations like Mg21, Mn21, Zn21, Ca21, Co21, Cu21, Na1, K1, etc.
are required for optimum activity of some of the enzymes;
e.g. chloride ions (Cl–) activate salivary amylase and Ca1
ions activate lipases. Two categories of enzymes requiring
metals for their activity are distinguished:
Metal-activated enzymes: The metal is not tightly
held by the enzyme and can be exchanged easily with other
ions, e.g. ATPase (Mg21 and Ca21), enolase (Mg21).
Metalloenzymes: These enzymes require certain
metal ions for their activity. The metals are tightly held by
the enzymes which are not readily exchanged, e.g. alcohol
dehydrogenase, carbonic anhydrase, alkaline phosphatase,
carboxypeptidase and aldolase contain zinc.
i. Phenol oxidase (copper) ii. Pyruvate oxidase
(manganese) iii. Xanthine oxidase (molybdenum) iv.
Cytochrome oxidase (iron and copper).
Different molecular forms of the same enzyme synthesized
from different tissues are called isoenzymes or isozymes.
They differ in their physical and chemical properties, such
SHORT ESSAYS
Q. 1. Isoenzymes.
Define isoenzymes. Name them (any three) and Or give their clinical importance.
as the structure, electrophoretic and immunological
properties; Km and Vmax values, pH, relative susceptibility to
inhibitors and degree of denaturation.
ISOENZYMES OF LDH
LDH has five isoenzymes; all the forms are present in the
same individual. It is a tetramer with four subunits, which
may be either H (heart) or M (muscle) polypeptide chains.
So five combinations of H and M chains are possible,
forming five isoenzymes as follows:
LDH1 — H4 LDH2 — H3M
LDH3 — H2M2 LDH4 — M3H LDH5 — M4
All the isoenzymes are seen in all persons in the
populations. Normally, LDH2 concentration is greater than
LDH1 in the blood. This pattern is reversed in myocardial
infarction, which is known as flipped pattern. In myocardial
infarction, total LDH activity is increased, while LDH1
isoenzyme is increased 5–10 times, which is of diagnostic
significance.
Isoenzymes of LDH have immense value in the diagnosis of
heart- and liver-related disorders.
ISOENZYMES OF CREATINE PHOSPHOKINASE
Creatine kinase (CK) or creatine phosphokinase (CPK)
catalyses the interconversion of phosphocreatine (or
creatine phosphate) to creatine.
CPK exists as three isoenzymes. Each isoenzyme is a dimer
composed of two subunits — M (muscle) or B (brain) or
both.
CPK1 — BB (brain)
CPK2 — MB (heart) CPK3 — MM (skeletal muscle).
The earliest reliable indication of myocardial infarction is
estimation of CPK2 (MB).
ISOENZYMES OF ALKALINE PHOSPHATASE
Alkaline phosphatase (ALP) has six isoenzymes. The most
important ALP isoenzymes are a1-ALP, a2-heat-labile
ALP, a2-heat-stable ALP, pre-b-ALP, g-ALP, etc. Increase
in a2-heat-labile ALP suggests hepatitis, whereas increased
pre-b-ALP indicates bone diseases. Q. 2. Classification
of enzymes. Or
Classification of enzymes with one example for
each class.
For classification of enzymes, refer to the answer of Long
Essays Q. 1.
Q. 3. Define competitive inhibition. Give three
examples.
Or
Features and examples for competitive and
feedback inhibition.
Or
Explain the competitive inhibition of enzymes with
examples.
The inhibitor, which is structurally similar to the substrate,
competes with the substrate for the active or binding sites
and thus diverts much of the enzyme to form the enzyme–
inhibitor complex instead of enzyme–substrate complex.
The enzyme–inhibitor complex will not yield any products
and hence remains stable, thus preventing further enzyme
activity. This is known as reversible or competitive
inhibition.
This type of an inhibition can be reversed by adding excess
of substrate, which will dislodge the inhibitor molecules
successfully from the enzymes.
The pharmacological action of several drugs is dependent
on the ability of the drugs to inhibit one or other of the
enzymes responsible for the growth and multiplication of
microorganisms.
Some examples of competitive inhibition are as follows:
 Biochemistry 263

Malonate, oxalate and glutarate can inhibit succinate Q. 4. Competitive inhibition and noncompetitive
dehydrogenase—all of them resemble the substrate, inhibition.
succinic acid, in structure.
Pressor amines like adrenaline and noradrenaline are COMPETITIVE INHIBITION
oxidized by monoamine oxidase. Ephedrine and The inhibitor (I), which closely resembles the real substrate
amphetamine, which have similar structure as that of (S), is regarded as a substrate analogue. The inhibitor
adrenaline and noradrenaline, inhibit the enzyme and thus competes with substrate and binds at the active site of the
prolong the action of the pressor amines. enzyme but does not undergo any catalysis. As long as the
Uric acid is formed by the oxidation of hypoxanthine by competitive inhibitor holds the active site, the enzyme is
xanthine oxidase. In gout, uric acid accumulates in tissues not available for the substrate to bind.
and causes symptoms. Allopurinol structurally resembles The relative concentration of the substrate and inhibitor and
hypoxanthine and by competitive inhibition decreases the their respective affinity with the enzyme determine the
formation of uric acid (Table 3.7.1). degree of competitive inhibition. The inhibition could be
Feedback regulation: In a series of enzyme- overcome by a high substrate concentration. In competitive
catalysed reactions of a metabolic pathway, the process of inhibition, the Km value increases whereas Vmax remains
inhibiting the first step by the final product is known as unchanged.
feedback regulation, e.g. in the series of reactions given The enzyme succinate dehydrogenase (SDH) is a classical
below, A is the initial substrate; B, C and D are the example of competitive inhibition with succinic acid as its
intermediates; and E is the end product. In a pathway substrate. Malonic acid has structural similarity with
catalysed by four different enzymes (E1, E2, E3, E4), the succinic acid and competes with the substrate for binding at
very first step (A n B catalysed by the enzyme E1) is most the active site of SDH.
effective for regulating the pathway by the final end COOH
product E. This type of control is called negative feedback CH2COOHCH2
regulation. CH2COOHCOOH
E1 E2 E3 E4 Succinic acid Malonic acid
A B C D E Some more examples of the enzymes with substrates and
Table 3.7.1 Competitive inhibition of enzymes competitive inhibitors of biological significance are given
Importance in Table 3.7.1.
Enzyme Substrate Inhibitor of inhibitor ANTIMETABOLITES
Xanthine Hypoxanthine Allopurinol Used in the These are the chemical compounds that block the metabolic
oxidase xanthine control of gout reactions by their inhibitory action on enzymes.
to reduce Antimetabolites are usually structural analogues of
excess
substrates, and thus are competitive inhibitors. They are in
production of
uric acid from use for the treatment of cancer, gout, etc. The term
hypoxanthine antivitamins is used for the antimetabolites, which block the
Monoamine Catecholamine Ephedrine, Useful for biochemical actions of vitamins, causing deficiencies, e.g.
oxidase s (epinephrine, amphetamin elevating sulphanilamide and dicumarol.
norepinephrine) e catecholamin NONCOMPETITIVE INHIBITION
e levels The inhibitor binds at a site other than the active site on the
Dihydrofolat Dihydrofolic Aminopterin, Employed in enzyme surface. This binding impairs the enzyme function.
e reductase acid amethopterin the treatment The inhibitor has no structural resemblance with the
, of leukaemia substrate. However, there usually exists a strong affinity for
methotrexate and other
the inhibitor to bind at the second site. In fact, the inhibitor
cancers
does not interfere with the enzyme-substrate binding. But
Feedback inhibition or end-product inhibition is a the catalysis is prevented, possibly due to a distortion in the
specialized type of allosteric inhibition necessary to control enzyme conformation.
metabolic pathways for efficient cellular function. The inhibitor generally binds with the enzyme as well as the
Aspartate transcarbamoylase (ATCase) is a good example ES complex. For noncompetitive inhibition, the K m value is
of an allosteric enzyme inhibited by a feedback mechanism. unchanged, while Vmax is lowered.
Carbamoyl phosphate undergoes a sequence of reactions for Heavy metal ions (Ag1, Pb21, Hg21, etc.) can
synthesis of the end product, CTP. When CTP accumulates,
noncompetitively inhibit the enzymes by binding with
it allosterically inhibits the enzyme aspartate
cysteinyl sulphhydryl groups.
transcarbamoylase by a feedback mechanism.
262 Quick Review Series: BDS 1st Year

Q. 5. Name five clinically important enzymes in Clinical significance: In acute pancreatitis and carcinoma of
plasma. Indicate their normal values and clinical pancreas plasma lipase levels are elevated and are
significance. decreased in liver disease, vitamin A deficiency and in
diabetes mellitus.
Estimation of enzyme activities in biological fluids (plasma/ Amylase
serum) is of great clinical importance. Certain enzymes are Normal value: 80–180 units (Somogyi units/dL) Clinical
normally present in the plasma and have specific functions significance: Plasma amylase is increased in acute
to perform. They are mostly synthesized in the liver and pancreatitis and in inflammatory conditions of the salivary
enter the circulation, and are known as plasma-specific or glands. It is decreased in liver disease.
plasma-functional enzymes, e.g: Alkaline phosphatase Normal value:
Lipase Adults: 1.5–5.0 units (Bodansky)
Normal value: 0.5–1.5 IU/L
5–10 units (King–Armstrong) Acid phosphatase
1.0–3.5 phenol units Normal value: 0–2.5 units (King–Armstrong)
Children: 5–14 units (Bodansky) 0–1.5 phenol units
15–20 units (King–Armstrong) Clinical significance: An elevation of its levels in plasma is
4–12 phenol units highly suggestive of prostatic carcinoma.
Clinical significance: Alkaline phosphatase is increased in Isocitrate dehydrogenase: Its levels are increased in
rickets, hyperparathyroidism, several diseases and plasma in liver disease.
disorders involving bone and in obstructive jaundice.
SHORT NOTES
Q. 1. LDH isoenzymes.
Some enzymes are produced in an inactive form, which can
Different molecular forms of the same enzyme, synthesized be activated when required. Many of the digestive enzymes
from different tissues are called isoenzymes. For isozymes of and enzymes concerned with blood coagulation fall in this
LDH, refer to answer of Short Essays Q. 1. Q. 2. Enzyme category, and their activation is brought about by
inhibition. specifications or by other enzymes, which are proteolytic,
e.g.:
+

Pepsinogen + H Pepsin
The process which makes the active site of the enzyme inef- Enterokinase
fective is known as
enzyme inhibition.
Enzyme inhibitor is a
substance which bindsQ. 4. Give the enzyme and cofactors necessary for transamination reaction.
with the enzyme and
brings about a decreaseEnzymes called ‘transaminases’ or ‘amino transferases’ catalyse the transfer of the amino group of
in catalytic activity of an amino acid to an a-keto acid to form a new amino acid and a new keto acid. Amino transferases
that enzyme. are present in the liver, kidney and the brain.
There are three broadThe reaction is not confined only to the formation of alanine and aspartic acid. Several other keto
categories of enzyme acids can be transaminated to form their corresponding amino acids.
inhibitions, which are as
follows:
Reversible inhibition or
competitive inhibition,
e.g. dicumarol and
vitamin K.
Irreversible inhibition or
noncompetitive
inhibition,
e.g. a variety of poisons
like iodoacetate, heavy
metals.
 Biochemistry 263

Allosteric inhibition, e.g.

allosteric enzymes.
Q. 3. What are
proenzymes? Give
two examples.
Mention their
significance.

Topic 8 BILE
Trypsinogen Trypsin

SHORT NOTE
Q. 1. Normal value of bile acids. Various bile acids are hydroxy derivatives of cholanic acid.
They are synthesized in the liver from cholesterol, e.g.
1. Cholic acid
Bile acids: 2. Deoxycholic acid
In hepatic: 1.93% 3. Chenodeoxycholic acid In gall bladder: 9.14% 4. Lithocholic acid.

Topic 9 HAEMOGLOBIN AND PORPHYRINS

SHORT NOTES
Q. 1. Haemoglobin. Haemoglobin
Globin
Amino acid
Haemoglobin is a red blood pigment found in erythrocytes. Heme pool
In
Its functions are as follows: macrophage
Transport of O2 from lungs to tissues Iron
Biliverdine
Excretion of CO2 from tissues through the lungs.
Biliverdine reductase
Normal haemoglobin concentration in blood: Males:
Bilirubin
14–16 g/dL Females: 13–15 g/dL Q. 2. Glycosylated
form of haemoglobin.
In blood Bilirubin–albumin complex
The nonenzymatic addition of any sugar residue to amino
acids of protein is called glycation. Glucose-derived
Bilirubin
products of normal adult haemoglobin refer to glycated or
glycosylated haemoglobin (HbA1c). In liver Bilirubin glucuronyl transferase
Measurement of HbA1c is used for monitoring diabetes Bilirubin diglucuronide (to bile)
control. It reflects mean blood glucose level over 2-month Microbial enzymes (intestine)

Urobilinogen
Kidney Intestine
Intestine
and kidney Urobilin Stercobilin

Urine Faeces
period prior to its measurement. It is the best index of
longterm control of blood glucose levels.
Normal concentration of HbA1c is 3–5% of total
haemoglobin. In diabetics, it is elevated to as high as 15%.
Q. 3. Degradation of heme.
262 Quick Review Series: BDS 1st Year

Heme is degraded by a complex microsomal enzyme interactions primarily hydrophobic, ionic and hydrogen
known as heme oxygenase. The end products of heme bonds.
catabolism are bile pigments known as biliverdin (a green STRUCTURE OF GLOBIN (FIG. 3.9.2)
pigment) and bilirubin (yellow pigment). Both of them are It consists of four polypeptide chains of two different
useless excretory products. monomeric units. The common form of adult haemoglobin
The entire degradation of heme is as shown in Fig. 3.9.1. Q. (HbA1) is made up of two a-chains and two b-chains.
4. Haemoglobin — structure and synthesis. STRUCTURE OF HEME
Heme is a porphyrin derivative known as protoporphyrin
Haemoglobin is a tetrameric conjugated protein consisting IX, with iron at its centre.
of globin — an apoprotein part and heme — the nonprotein
part or prosthetic group. Four subunits of haemoglobin β β
(Fig. 3.9.1), each one with a prosthetic heme group and the α
globin polypeptide are held together by noncovalent α
Fig. 3.9.1 Degradation of
heme. Fig. 3.9.2
Structure
haemoglobin.
of URINE
Topic 10
SHORT NOTES
Q. 1. Normal value of blood urea. Ketone bodies, i.e. acetone and acetoacetate are detected by
Rothera’s test, where nitroprusside in alkaline medium re-
acts with keto group of ketone bodies to form a purple ring.
Normal value of blood urea is 15–40 mg/dL. Proteins in the urine are detected by sulphosalicylic acid Q. 2. Write the
tests to identify the following in test and heat coagulation test. In sulphosalicylic acid test, urine: proteins get
precipitated by sulphosalicylic acid, forming a. Ketone bodies protein-sulphosalicylate. Heat coagulation test is used for
b. Proteins. the detection of albumin and globulins in the urine. This test
is based on the principle of denaturation of proteins fol-
lowed by
coagulation.
ORGAN FUNCTION TESTS
Topic 11
SHORT NOTE
Q. 1. Normal value of serum alkaline phosphatase. 3–13 units (King–Armstrong)/dL
1.0–3.5 phenol units/dL
Normal value of serum alkaline phosphatase in adults: Children: 5–14 units (Bodansky)/dL
1.5–5.0 units (Bodansky)/dL 15–20 units (King–Armstrong)/dL
4–12 phenol units/L

Topic 12
SHORT NOTES
Q. 1. Pancreatic hormones. Thromboxane is a main prostaglandin released by platelets.
Major effects of thromboxanes are as follows:
Insulin and glucagon are the pancreatic hormones produced Vasoconstriction
by the beta cells of
islets of Langerhans
and alpha cells of
HORMONES
pancreas, respectively. Promote platelet aggregation
Blood clotting (leading to thrombosis).
Q. 2. Thromboxane.

Topic 13 NUTRITION AND DIET

 Biochemistry 263

SHORT NOTE
Q. 1. Importance of milk in our daily diet. Three types of proteins in the milk are casein, albumin
and globulin. Casein has high biological value. Lactoglobu-
lin produces immunity in children during breastfeeding.
From the point of nutrition, milk is considered as complete Milk contains large amounts of calcium, phosphorus, natural
food. Generally, milk contains 80–90% of water. vitamin A and riboflavin. Major nutrients lacking in milk are Among the
various nutrients, carbohydrates (lactose), fats iron, copper and vitamin C. and proteins are the major constituents of milk.
SHORT NOTES
Q. 1. What is calorie? Mention the caloric value of calorimeter are 4.1, 9.4 and 5.4 cal/g and when utilized in
carbohydrates, proteins and fat. the body are 4.0, 9.0 and 4.0 cal/g, respectively. Q. 2.
Balanced diet.
Calorie is the unit of heat. One calorie represents the
amount of heat required to raise the temperature of 1 g A diet which provides quantitatively and qualitatively
water by 1°C. adequate amount of all principal foods for maintaining a
CALORIC VALUE OF FOODS good health of an individual is known as balanced diet.
The energy values of the three principal foodstuffs — In a balanced diet, carbohydrates should provide 65–75%,
carbohydrate, fat and protein — measured in a bomb lipids about 20% and proteins about 10–15% of the
required calories.
Q. 1. Classify vitamins. Indicate dietary sources, The fat-soluble vitamin A, as such, is present only in foods
daily requirements and deficiency symptoms of of animal origin. However, its provitamins, carotenes, are
fat-soluble vitamins. Briefly explain the role of found in plants.
vitamin A in vision. Biochemical functions
Retinol and retinoic acid function almost like steroid
The vitamins are classified as follows (Fig. 3.14.1). hormones. They regulate the protein synthesis and thus are
FAT-SOLUBLE VITAMINS involved in the cell growth and differentiation.
The four vitamins, namely, vitamin A, D, E and K are Vitamin A is essential to maintain healthy epithelial tissue.
known as fat or lipid soluble. Their availability in the diet, Carotenoids (most important is b-carotene) function as
absorption, and transport are associated with fat. They are antioxidants and reduce the risk of cancers initiated by free
soluble in fats and oils, and also the fat solvents (alcohol, radicals and strong oxidants. b-Carotene is found to be

VITAMINS
Topic 14
LONG ESSAYS
acetone, etc.). Fat-soluble vitamins can be stored in liver beneficial to prevent heart attacks. This is also attributed to
and adipose tissue. the antioxidant property.
Vitamin A Dietary sources
Animal sources contain (preformed) vitamin A. The best
sources
Vitamins are liver,
kidney,
Fat soluble Water soluble egg yolk,
milk,
Vitamin A
Non-B-complex B-complex cheese,
Vitamin D
Vitamin E Vitamin C
Vitamin K Energy-releasing Haematopoietic

Thiamine (B1) Folic acid

Riboflavin (B2) Vitamin (B12)
Niacin (B3) (cyanocobalamin)

Pyridoxine (B6)
Biotin (B7)
Pantothenic acid
Fig. 3.14.1 Classification of vitamins.
262 Quick Review Series: BDS 1st Year
butter. Fish (cod or shark) liver oils are very rich in vitamin
A.
Vegetable sources contain the provitamin A—carotenes.
Yellow and dark green vegetables and fruits are good
sources of carotenes, e.g. carrots, spinach, Amaranthus,
pumpkins, mango, papaya, etc.
Recommended dietary allowance
The recommended dietary allowance (RDA) of vitamin A
for adults is around 1000 retinol equivalents (5000 IU) for
man and 800 retinol equivalents (4000 IU) for woman. One
international unit (IU) is equivalent to 0.3 µg of retinol. The
requirement increases in growing children, pregnant
women, and lactating mothers.
Vitamin A deficiency
Deficiency manifestations of the eyes:
Night blindness (nyctalopia) is one of the earliest
symptoms of vitamin A deficiency. The individuals have
difficulty to see in dim light.
Severe deficiency of vitamin A leads to xerophthalmia.
This is characterized by dryness in conjunctiva and cornea,
and keratinization of epithelial cells. In certain areas of
conjunctiva, white triangular plaques known as Bitot’s
spots are seen.
If xerophthalmia persists for a long time, corneal ulceration
and degeneration occur. This results in the destruction of
cornea, a condition referred to as keratomalacia, causing
total blindness. Vitamin A deficiency blindness is most
common in children of the developing countries.
Vitamin D
Vitamin D is a fat-soluble vitamin. It resembles sterols in
structure and functions as does a hormone.
Recommended dietary allowance
The daily requirement of vitamin D is 400 IU or 10 g of
cholecalciferol. In countries with good sunlight (like India),
the RDA for vitamin D is 200 IU (or 5 µg of
cholecalciferol).
Dietary sources
Good sources of vitamin D include fatty fish, fish liver oils,
egg yolk, etc. Milk is not a good source of vitamin D.
Deficiency symptoms
Deficiency of vitamin D leads to demineralization of bone.
The result is rickets in children and osteomalacia in adults.
Rickets is derived from an old English word wrickken,
meaning to twist. Osteomalacia is derived from Greek
(osteon, bone; malakia, softness). Vitamin D is often called
as antirachitic vitamin.
Rickets in children is characterized by bone deformities due
to incomplete mineralization, resulting in soft and pliable
bones and delay in teeth formation. In rickets, the plasma
level of calcitriol is decreased and alkaline phosphatase
activity is elevated.
In case of osteomalacia (adult rickets), demineralization of
the bones occurs (bones become softer), thereby increasing
their susceptibility to fractures.
Renal rickets (renal osteodystrophy)
This is seen in patients with chronic renal failure. Renal
rickets is mainly due to decreased synthesis of calcitriol in
kidney. It can be treated by administration of calcitriol.
Vitamin E
Vitamin E (tocopherol) is a naturally occurring antioxidant.
It is essential for normal reproduction in many animals,
hence is known as antisterility vitamin.
Recommended dietary allowance
A daily consumption of about 10 mg (15 IU) of a-
tocopherol for men and 8 mg (12 IU) for women is
recommended; 1 mg of a-tocopherol is equal to 1.5 IU.
Vitamin E-supplemented diet is advised for pregnant and
lactating women.
Deficiency symptoms
The symptoms of vitamin E deficiency vary from one
animal species to another. In many animals, the deficiency
is associated with sterility, degenerative changes in muscle,
megaloblastic anaemia and changes in central nervous
system.
VITAMIN K
Vitamin K is the only fat-soluble vitamin with a specific
coenzyme function. It is required for the production of
blood clotting factors, essential for coagulation (in German,
koagulation; hence, the name K for this vitamin).
Dietary sources
Cabbage, cauliflower, tomatoes, alfalfa, spinach and other
green vegetables are good sources of vitamin K. It is also
present in egg yolk, meat, liver, cheese and dairy products.
Biochemical functions
The functions of vitamin K are concerned with blood
clotting process. It brings about the post-translational (after
protein biosynthesis in the cell) modification of certain
blood clotting factors. The clotting factors II (prothrombin),
VII, IX and X are synthesized as inactive precursors
(zymogens) in the liver. Vitamin K acts as a coenzyme for
the carboxylation of glutamic acid residues present in the
proteins, and this reaction is catalysed by a carboxylase
(microsomal).
Recommended dietary allowance
Strictly speaking, there is no RDA for vitamin K, since it
can be adequately synthesized in the gut. It is, however,
recommended that half of the body requirement is provided
in the diet, while the other half is met from the bacterial
synthesis. Accordingly, the suggested RDA for an adult is
70–140 µg/day.
Deficiency symptoms
The deficiency of vitamin K is uncommon, since it is
present in the diet in sufficient quantity and/or is adequately
synthesized by the intestinal bacteria.
Deficiency of vitamin K leads to the lack of active
prothrombin in the circulation. Therefore blood coagulation
is adversely affected. The individual bleeds profusely even
for minor injuries. The blood clotting time is increased.
 Biochemistry 263

Q. 2. Describe the sources and daily requirements contains three hydroxyl groups (1, 3, and 25 carbon) and
of vitamin D, and write a note on its deficiency. hence is referred to as calcitriol.
BIOCHEMICAL FUNCTIONS
Refer to the answer of Long Essays Q. 1. Calcitriol (1,25 DHCC) is the biologically active form of
Q. 3. Enumerate the functions of vitamin D. vitamin D. It regulates the plasma levels of calcium and
Explain its importance in calcium metabolism. phosphate. Calcitriol acts at three different levels (intestine,
kidney and bone) to maintain plasma calcium.
Vitamin D is a fat-soluble vitamin. It resembles sterols in Action of calcitriol on the
structure and functions as does a hormone. intestine: Calcitriol increases the intestinal
METABOLISM AND BIOCHEMICAL FUNCTIONS absorption of calcium and phosphate. In the intestinal cells,
OF VITAMIN D calcitriol binds with a cytosolic receptor to form a
Vitamins D2 and D3 as such are not biologically active. calcitriol–receptor complex. This complex then approaches
They are metabolized identically in the body and converted the nucleus and interacts with a specific DNA, leading to
to active forms of vitamin D. The metabolism and the synthesis of a specific calcium-binding protein. This
biochemical functions of vitamin D are depicted in Fig. protein increases the calcium uptake by the intestine.
3.14.2. Action of calcitriol on the bone:
UV light Skin In the osteoblasts of bone, calcitriol stimulates
7-Dehydrocholesterol
calcium uptake for deposition as calcium phosphate. Thus,
Cholecalciferol calcitriol is essential for bone formation.
Liver
Cholecalciferol
25-Hydroxylase
25-Hydroxy-
cholecalciferol

Kidney
25-Hydroxy-
cholecalciferol
PTH 1-Hydroxylase
Low phosphate

1.25 DHCC
(calcitriol)
Ca, P↑
absorption
Bone
Intestine
Calcitriol ( )
Receptor( )
Calcitriol
receptor
complex ( )
Calcitriol
Bone formation
and turnover
mRNA

Calcium binding
protein
Plasma
Ca2+ Ca2+
absorption
Fig. 3.14.2 Metabolism and biochemical functions of vitamin D.
Synthesis of 1,25 DHCC: Cholecalciferol
is first hydroxylated at 25th position to 25-
hydroxycholecalciferol (25-OH D3) by a specific
hydroxylase present in liver, which is the major storage and
circulatory form of vitamin D. Kidneys possess a specific
enzyme, 25-hydroxycholecalciferol 1–hydroxylase, which
hydroxylates 25-hydroxycholecalciferol at position 1 to
produce 1,25-dihydroxycholecalciferol (1,25 DHCC). It
262 Quick Review Series: BDS 1st Year

Action of calcitriol on the kidney: excretion of calcium and phosphate through the kidney by
Calcitriol is also involved in minimizing the decreasing their excretion and enhancing reabsorption.
Q. 1. Ascorbic acid. vitamin A, vitamin E and some B-complex vitamins from
Or oxidation.
Functions and deficiency of vitamin C. Immunological function: Vitamin C enhances the
Or Functions and deficiency of ascorbic acid. synthesis of immunoglobulins (antibodies) and increases

SHORT ESSAYS
VITAMIN C (ASCORBIC ACID)
Vitamin C is a water-soluble versatile vitamin. It plays an
important role in human health and disease.
Biochemical functions
Most of the functions of vitamin C are related to its
property to undergo reversible oxidation–reduction, i.e.
interconversion of ascorbic acid and dehydroascorbic acid.
Collagen formation: Vitamin C plays the role
of a coenzyme in hydroxylation of proline and lysine, while
protocollagen is converted to collagen (i.e. post-
translational modification). The hydroxylation reaction is
catalysed by lysyl hydroxylase (for lysine) and prolyl
hydroxylase (for proline). This reaction is dependent on
vitamin C.
Hydroxyproline and hydroxylysine are essential for the
collagen cross-linking and the strength of the fibre. In this
way, vitamin C is necessary for maintenance of normal
connective tissue and wound healing process.
Bone formation: Bone tissues possess an organic
matrix, collagen and the inorganic calcium, phosphate, etc.
Vitamin C is required for bone formation.
Iron and haemoglobin metabolism:
Ascorbic acid enhances iron absorption by keeping
it in the ferrous form.
This is due to the reducing property of vitamin C.
Tryptophan metabolism: Vitamin C is essential for
the hydroxylation of tryptophan (enzyme, hydroxylase) to
hydroxytryptophan in the synthesis of serotonin.
Tyrosine metabolism: Ascorbic acid is required
for the oxidation of p-hydroxyphenylpyruvate (enzyme,
hydroxylase) to homogentisic acid in tyrosine metabolism.
Folic acid metabolism: The active form of the
vitamin folic acid is tetrahydrofolate (FH 4). Vitamin C is
needed for the formation of FH4 (enzyme, folic acid
reductase).
Synthesis of corticosteroid hormones:
Adrenal gland possesses high levels of ascorbic
acid, particularly in periods of stress. It is believed that
vitamin C is necessary for the hydroxylation reactions in
the synthesis of corticosteroid hormones.
Sparingaction of other vitamins:
Ascorbic acid is a strong antioxidant. It spares
Essays Q. 1.
Q. 4. Vitamin A deficiency.
Or Deficiency manifestations of vitamin A.
the phagocytic action of leucocytes.
1 0. Preventive action on chronic diseases:
Free radicals are constantly produced in the normal
metabolism. They cause serious damage to proteins, lipids,
DNA and the cell membranes. The free radicals are
implicated in the development of cancer, heart diseases and
also ageing. Vitamin C is a strong biological antioxidant,
besides vitamin E and b-carotene.
Deficiency symptoms
The deficiency of ascorbic acid results in scurvy. This
disease is characterized by spongy and sore gums, loose
teeth, anaemia, swollen joints, decreased
immunocompetence, delayed wound healing, haemorrhage,
osteoporosis, etc.
Q. 2. Vitamin D deficiency.
Deficiency symptoms: For deficiency symptoms, refer to
the answer of Long Essays Q. 1.
Q. 3. Biological functions of vitamin A. Or
Describe the functions of vitamin A.
Biochemical functions of vitamin A: Vitamin A is
necessary for a variety of functions such as vision, proper
growth and differentiation, reproduction and maintenance
of epithelial cells. For biochemical functions, refer to the
answer of Long reactions like transamination,
decarboxylation, deamination, transsulphuration,
condensation, etc.
Transamination: PLP is involved in the
transamination reaction (by transaminase), converting
amino acids to keto acids.
Decarboxylation: Some of the a-amino acids
undergo decarboxylation to form the respective amines.
This is carried out by a group of enzymes called
decarboxylases, which are dependent on PLP. Many
biogenic amines with important functions are synthesized
by PLP decarboxylation.
Serotonin (5-hydroxytryptamine, 5-HT) produced from
tryptophan is important in nerve impulse transmission
(neurotransmitter). It regulates sleep, behaviour, blood
pressure, etc.
Refer to the answer of Long Essays Q. 1.
Q. 5. Coenzyme forms and deficiency of niacin.
 Biochemistry 263

Niacin or nicotinic acid is also known as pellagra- Wald’s visual cycle: Rhodopsin is a conjugated protein
preventive (PP) factor of Goldberg. The coenzymes of present in rods. It contains 11-cis retinal and the protein
niacin (NAD1 and NADP1) can be synthesized by the opsin.
essential amino acid tryptophan. The primary event in visual cycle, on exposure to light, is
Deficiency symptoms: Niacin deficiency results the isomerization of 11-cis retinal to all-trans retinal. This
in a condition called pellagra (Italian, rough skin). The leads to a conformational change in opsin, which is
disease pellagra involves skin, gastrointestinal tract and responsible for the generation of nerve impulse. The
central nervous system. The symptoms of pellagra are alltrans retinal is immediately isomerized by retinal
commonly referred to as three Ds. The disease also isomerase (of retinal epithelium) to 11-cis retinal, which
progresses in that order dermatitis, diarrhoea, dementia combines with opsin to regenerate rhodopsin and this
and, if not treated, may rarely lead to death (fourth D). completes the visual cycle. However, the conversion of
Q. 6. Biological functions of pyridoxine. alltrans retinal to 11-cis retinal is incomplete. Therefore,
most of the all-trans retinal is transported to the liver and
PYRIDOXINE (VITAMIN B6) converted to all-trans retinol by alcohol dehydrogenase.
Vitamin B6 is used to collectively represent the three The all-trans retinol undergoes isomerization to 11-cis
compounds, namely, pyridoxine, pyridoxal and retinol, which is then oxidized to 11-cis retinal to
pyridoxamine. participate in the visual cycle (Fig. 3.14.3).
Biochemical Functions Q. 8. How does vitamin K take part in the
Pyridoxal phosphate (PLP), the coenzyme of vitamin B 6 is coagulation of blood?
found attached to the -amino group of lysine in the
enzyme. PLP is closely associated with the metabolism of Vitamin K is the only fat-soluble vitamin with a specific
amino acids. The synthesis of certain specialized products coenzyme function. It is required for the production of
such as serotonin, histamine and niacin coenzymes from the blood clotting factors, which are essential for coagulation
amino acids is dependent on pyridoxine. PLP participates in (in German, koagulation; hence the name K for this
PLP vitamin).
Tryptophan 5-Hydroxytryptophan Light
Rhodopsin
CO2 5-Hydroxytryptamine (photon)
(11-cis-retinal
The synthesis of catecholamines (dopamine, norepinephrine -opsin)
and epinephrine) from tyrosine requires PLP.
Catecholamines are involved in metabolic and nervous Nerve
impulse
regulation.
PLP
Tryptophan DOPA Dopamine CO2
Opsin
Norepinephrine Epinephrine
PLP is required for the synthesis of d-amino levulinic acid
Retinal
—the precursor for heme synthesis. Isomerase
11- cis-retinal All-trans-retinal
Glycine Ala synthase

NADH + H+
Succinyl CoA PLP δlevulinic -Amino Heme acid Alcohol
NADH + H+ Alcohol
(ALA) dehydrogenase dehydrogenase
PLP plays an important role in the metabolism of sulphur- NAD− NAD− (liver)
containing amino acids. Trans-sulphuration (transfer of
Isomerase
sulphur) from homocysteine to serine occurs in the 11- cis-retinal All-trans-retinal
(liver)
synthesis of cysteine.
Fig. 3.14.3 Visual cycle.
Deamination of hydroxyl-group-containing amino acids
requires PLP. The functions of vitamin K are concerned with blood
clotting process. It brings about the post-translational (after
Serine DehydratasePLP Pyruvate NH3 Threonine
protein biosynthesis in the cell) modification of certain
Dehydratase
PLP α-Ketobutyrate NH3 blood clotting factors. The clotting factors II (prothrombin),
Serine is synthesized from glycine by a PLP-dependent VII, IX and X are synthesized as inactive precursors
enzyme hydroxymethyltransferase. Q. 7. Visual cycle. (zymogens) in the liver.

SHORT NOTES
262 Quick Review Series: BDS 1st Year
Q. 1. Pellagra.
Niacin deficiency results in a condition called pellagra
(Italian, rough skin). The disease pellagra involves skin,
gastrointestinal tract and central nervous system. The
symptoms of pellagra are commonly referred to as three
D’s. The disease also progresses in that order dermatitis,
diarrhoea, dementia, and, if not treated, may rarely lead to
death (fourth D). Q. 2. Vitamin C.
Or
Enumerate two biochemical functions of vitamin
C.
Vitamin C is a water-soluble versatile vitamin. It plays an
important role in human health and disease. Biochemical
Functions: Refer to the answer of Short Essays Q. 1.
Q. 3. Vitamin D. Or
Vitamin D deficiency.
Vitamin D is a fat-soluble vitamin. It resembles sterols in
structure and functions as does a hormone.
Deficiency of vitamin D leads to demineralization of bone.
The result is rickets in children and osteomalacia in adults.
Vitamin D is often called as antirachitic vitamin. Q. 4.
Vitamin K.
Vitamin K is the only fat-soluble vitamin with a specific
coenzyme function. It is required for the production of
blood clotting factors, which are essential for coagulation
(in German, koagulation; hence the name K for this
vitamin). Q. 5. Fat-soluble vitamins.
The four vitamins, namely, vitamin A, D, E and K are
known as fat or lipid soluble. Their availability in the diet,
absorption and transport are associated with fat. They are
soluble in fats and oils, and also the fat solvents (alcohol,
acetone, etc.). Fat-soluble vitamins can be stored in liver
and adipose tissue.
Q. 6. List four features of vitamin A deficiency. Or
Describe the features of deficiency of vitamin A.
Or Deficiency diseases of vitamin A.
Refer to the answer of Long Essays Q. 1.
Q. 7. Coenzymes of riboflavin and niacin.
Flavin mononucleotide (FMN) and flavin adenine
dinucleotide (FAD) are the coenzyme forms of riboflavin,
and NAD1 and NADP1 are the coenzyme forms of niacin.
Q. 8. What are the diseases caused by deficiency
of (a) niacin and (b) vitamin B12 (cobalamin)?
Niacin deficiency results in a condition called pellagra
(Italian, rough skin). The disease pellagra involves skin,
gastrointestinal tract and central nervous system. The
symptoms of pellagra are commonly referred to as three
D’s. The disease also progresses in that order dermatitis,
diarrhoea, dementia, and if not treated, may rarely lead to
death (fourth D).
The most important disease associated with vitamin B I2
deficiency is pernicious anaemia. It is characterized by low
haemoglobin levels, decreased number of erythrocytes and
neurological manifestations.
The excretion of methylmalonic acid (elevated) in urine and
estimation of serum B12 level are used to assess B12
deficiency. Q. 9. Explain the role of thiamine.
Thiamine (anti-beriberi or antineuritic vitamin) is water
soluble. It has a specific coenzyme, thiamine
pyrophosphate (TPP), which is mostly associated with
carbohydrate metabolism.
TPP plays an important role in the transmission of nerve
impulse. It is believed that TPP is required for acetylcholine
synthesis and the ion translocation of neural tissue.
Q. 10. Importance of folic acid in human diet.
Folic acid or folacin (Latin, folium: meaning leaf) is
abundantly found in green leafy vegetables. It is important
for one-carbon metabolism and is required for the synthesis
of certain amino acids, purines and the pyrimidine thymine.
Q. 11. Source and function of vitamin B12.
Vitamin B12 is also known as antipernicious anaemia
vitamin. It is a unique vitamin, synthesized by only
microorganisms, and not by animals and plants. It was the
last vitamin to be discovered.
Q. 12. Name the vitamins necessary for
neurological functions.
The vitamins necessary for neurological functions are as
follows:
Thiamine (vitamin B1)
Pyridoxine (vitamin B6)
Q. 13. Coenzymes of niacin and pyridoxine.
Nicotinamide adenine dinucleotide (NAD1) and
nicotinamide adenine dinucleotide phosphate (NADP1) are
the coenzymes of niacin.
PLP is the coenzyme of vitamin pyridoxine (vitamin B6).
BIOCHEMISTRY
VIVA QUESTIONS
Name a sugar that is characterized by its What is the limiting factor for fatty acid
nonreducing property; it is also called synthesis? Acetyl-CoA
cane sugar or table sugar. Sucrose. carboxylase.

Give the number of asymmetric carbon Which is the base that is not found in
atoms in glucose. DNA? Uracil.
Four. On complete hydrolysis of DNA, what
Which carbohydrate has b-1,4-glycosidic will we get?
bond? Lactose. Deoxy pentose sugar,
Name a homopolysaccharide made up of phosphoric acid and purine bases.
fructose. Inulin. DNA double helix is bound by which
Name a milk sugar. Lactose. bond? Hydrogen bond.
Name aglycone portion in methyl rRNA is mainly produced in which
glucoside. Methanol. component of the cell? Nucleolus.
Mucopolysaccharides are also known as In Niemann–Pick disease, which
Glycosaminoglyc substance accumulates in CNS in excess?
Monosaccharides can be separated by Phosphosphingosides.
which process? Chromatography. Mention the characteristics of the genetic
In fructofuranose, which is an anomeric code.
carbon atom? Carbon 2. The genetic code is universal,
Name an amino acid having no nonoverlapping and it degenerates.
asymmetric carbon atom. Glycine. Ketone body formation takes place in
Name few nonessential amino acids. which organ? Liver.
Alanine, cysteine and proline. Which element is known to influence the
Albumins and globulins are what type of body’s ability to handle oxidative stress?
proteins? Simple proteins. Selenium.
How are amino acids separated? Which group of proteins assists in folding
High voltage electrophoresis is of other proteins?
used to separate amino acids. Chaperones.
Name the process of transfer of In oxidative phosphorylation, which
information from the RNA to the method links the ATP production and
proteins. respiratory chain?
Translation. Chemiosmotic methods.
Name the precursor of melanin. Name an element having the lowest
Tyrosine. redox potential. Hydrogen.
How does an amino acid exist at a pH Name the compound having the highest
below the isoelectric point? redox potential. Cytochrome c.
Cation. What is the standard free energy of
Name few polyunsaturated fatty acids. hydrolysis of ATP into ADP and Pi?
Linoleic acid, linolenic acid –7.3 kcal/mol.
and arachidonic acid. Which substances poison cytochrome
Where does fatty acid oxidation occur? oxidase?
Cytoplasm, microsomes and Carbon monoxide, hydrogen
mitochondria. sulphide and cyanide.
Name an omega-3 polyunsaturated fatty Name few diseases caused by
acid. a-Linolenic acid. deficiencies of water-soluble vitamins.
Name a good source of polyunsaturated Beriberi, pellagra, scurvy, etc.
fatty acids. Cottonseed oil. How much proportion of the total body
What is the most important role of calcium is present in bones and teeth?
cholesterol? 99%.
Cholesterol is a component of What is the normal range of plasma
cell membrane. calcium? 9–11 mg/dL.
Where does cerebronic acid present? What is the normal range of ionized
Galactosyl ceramide. calcium in plasma? 4–5 mg/dL.
310 Quick Review Series: BDS 1st Year

Name the causes of tetany.

Hypocalcaemia and alkalosis.
How many iron atoms are contained by
each haemoglobin molecule?
Four iron atoms.
Which substance hampers the absorption
of calcium? Phytate.
Name a coenzyme that takes part in
hydrogen transfer reactions.
Coenzyme Q.
Which coenzyme is required in
transamination reactions? Pyridoxal
phosphate.
What is the pH of pancreatic juice?
The pH of pancreatic juice
varies from 7 to 8.
Which is the reliable test for glomerular
filtration rate? Inulin clearance test.
Normal blood pH is 7.38–7.4.
Where does the synthesis of protein
occur? Polyribosomes.
What does the people consuming
polished rice as their staple food prone to
develop? Beriberi.
Detoxification of drugs is controlled by
Cytochrome P450.