BIOCHEMISTRY SHORT ANSWER

1. Beri - Beri:
• The deficiency of vitamin B1 results in a condition called beriberi. Deficiency of
thiamine occurs in population who consume exclusively polished rice as staple food.
Polishing of rice removes thiamine.
• The early symptoms of thiamine deficiency are anorexia, nausea, mental confusion,
peripheral neuritis, muscle fatigue and irritability.
• Thiamine deficiency leads to three types of beriberi namely
1. Dry beriberi
2. Wet beriberi
3. Infantile beriberi
Dry beriberi (neuritic beriberi)
• It develops when the diet chronically contains slightly less than the thiamine
requirements.
• This form of beriberi is characterized primarily by peripheral neuritis, severe
muscular weakness and fatigue. Other symptoms of dry beriberi include dry skin,
mental confusion and poor appetite.
Wet beriberi (cardiac beriberi)
• It develops when the deficiency is more severe in which cardiovascular system is
affected in addition to neurological symptoms.
• Wet beriberi is characterized primarily by edema of extremities, heart enlargement
and cardiac insufficiency. Other symptoms include tachycardia or bradycardia and
palpitation.
• Both forms of beriberi may overlap to a varying degree and patients of beriberi may
die due to heart failure, if not treated.
Infantile beriberi
• Infantile beriberi is observed in breast fed infants born to mother suffering from
thiamine deficiency. The breast milk of these mothers is deficient in thiamine.
• It is characterized by cardiac dilation (enlargement of heart), tachycardia,
convulsions, edema and GI disturbances such as vomiting, abdominal colic, etc. In
acute condition, the infant may die due to cardiac failure.
Wernicke-Korsakoff Syndrome
• It is also known as cerebral beriberi and mostly seen in alcoholics.
• In chronic alcoholics, the nutritional deficiencies result from either poor intake of
food or malabsorption of nutrients from intestine.
• Wernicke-Korsakoff syndrome is characterized by anorexia, nausea, vomiting,
nystagmus, depression, ataxia, loss of memory, mental confusion, peripheral
paralysis, muscular weakness

2. Anti oxidant vitamins:

• Vitamin C:
Ascorbic acid is a water soluble antioxidant: (Ascorbic acid is a strong reducing agent
and acts as an antioxidant).
– It reduces oxidized vitamin E (tocopherol) to regenerate functional vitamin E.
– Vitamin C, thought to be involved in the prevention of atherosclerosis and
coronary heart disease by preventing oxidation of LDL.

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 – Antioxidant property of vitamin C is also associated with prevention of cancer by
inhibiting nitrosamine formation from naturally occurring nitrates during digestion.
• Vitamin A:
– β-carotene is involved in antioxidant function.
• Vitamin E:
- Vitamin E acts as a natural antioxidant by scavenging free radicals and molecular
oxygen.
- Vitamin E also helps to prevent oxidation of LDL. Oxidized LDL may be more
atherogenic than native LDL and thus vitamin E may protect against athreo- matous
coronary heart disease.

3. Rickets:
• Rickets is characterized by formation of soft and pliable bones due to poor mineralization
and calcium deficiency. Due to softness, the weight bearing bones are bent and deformed.
• The main features of the rickets are, a large head with protruding forehead, pigeon chest,
bow legs, (curved legs), knock knees and abnormal curvature of the spine (kyphosis).
• Rachitic children are usually anemic or prone to infections. Rickets can be fatal when
severe.
• Rickets is characterized by low plasma levels of calcium and phosphorus and high
alkaline phosphatase activity.

4. Pantothenic acid:
Structure:
Pantothenic acid is formed by a combination of pantoic acid and β-alanine (Figure 7.5).
Active form:
Active forms of pantothenic acid are:
• Coenzyme-A (CoA-SH)
• Acyl carrier protein (ACP)
Source:
Eggs, liver, yeast, wheat germs, cereals, etc. are important sources of pantothenic acid,
although the vitamin is widely distributed.
Functions:
• Pantothenic acid is a component of coenzyme-A (CoA- SH) and acyl carrier protein
(ACP). The thiol (-SH) group of CoA-SH and ACP acts as a carrier of acyl groups.
• Coenzyme-A participates in reactions concerned with:
– Reactions of citric acid cycle
– Fatty acid synthesis and oxidation
– Synthesis of cholesterol
– Utilization of ketone bodies.
• ACP participate in reactions concerned with fatty acid synthesis.
Nutritional Requirement:
The RDA of pantothenic acid is not well established. A daily intake of about 5–10 mg is
advised for adults.

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Deficiency Manifestations
No clearcut case of pantothenic acid deficiency has been reported (becuase the substance is
widely distributed in foods) except in malnourished prisoners of war in the far East in
1940s, where neurological condition, known as the burning feet syndrome, was reported
and ascribed to pantothenic acid deficiency. As these people were severely malnourished
and were deficient in other vitamins as well, it is not possible to attribute this specific effect
to pantothenic acid deficiency.
Clinical signs observed in experimentally induced deficiencies are:
• Paresthesia (abnormal tingling sensation)
• Headache
• Dizziness
• Gastrointestinal malfunction

5. Pellagra:
• Deficiency of niacin in human causes pellagra, a disease involving the:
• Skin
• Gastrointestinal tract
• Central nervous system.
• The symptoms of pellagra are characterized by three ‘Ds’:
1. Dermatitis
2. Diarrhea
3. Dementia and if not treated death.
Dermatitis: Skin inflammation is seen in any area exposed to direct sunlight.
Diarrhea: Frequent diarrhea nausea, vomiting, anorexia are the disorders of GI tract.
Dementia: Dementia (loss of memory) is associated with degeneration of nervous tissues.

6. Vitamin E and Vitamin K:

Vitamin E (Tocopherol) Structure
Vitamin E consists of eight naturally occurring tocopherols, of which α-tocopherol is the
most active form
Sources
The major dietary sources of vitamin E are fats and oils. The richest sources are germ oil,
corn oil, fish oil, eggs, lettuce and alfalfa.
Absorption, Transport and Storage
Vitamin E is absorbed from intestine together with dietary lipid. It is incorporated in
chylomicrons. It is delivered to the liver via chylomicron. The liver can export vitamin E
into very low density lipoprotein (VLDL) to target cells. In cells, tocopherols are distributed
where antioxidant activity is required. The major site of vitamin E storage is in the adipose
tissue.
Functions
• Vitamin E acts as a natural antioxidant by scavenging free radicals and molecular oxygen.
• Vitamin E is important for preventing peroxidation of polyunsaturated fatty acids in cell
membranes.
• Protection of erythrocyte membrane from oxidant is the major role of vitamin E in
humans. It protects the RBCs from hemolysis.
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• Vitamin E also helps to prevent oxidation of LDL. Oxidized LDL may be more
atherogenic than native LDL and thus vitamin E may protect against athreomatous coronary
heart disease.
• Whether vitamin E affects human fertility is unknown.
• In animals, vitamin E is required for normal reproduction and prevents sterility.
Nutritional Requirements
A daily consumption of about:
• 10 mg (15 IU) of α-tocopherol for a man
• 8 mg (12 IU) for a woman is recommended. One mg of α-tocopherol is equal to 1.5
IU.
Deficiency Manifestation
Vitamin E deficiency in humans is rare.
• The major symptom of vitamin E deficiency in human is hemolytic anemia due to an
increased red blood cell fragility.
• Another symptom of vitamin E deficiency is
retrolental fibroplasia (RLF) observed in some premature infants of low birth
weight. Children with this defect show neuropathy.

Vitamin K:
Structure
• There are two naturally occurring forms of vitamin K:
i. Vitamin K1 or phylloquinone derived from plant.
ii. Vitamin K2 or menaquinones, produced by microorganisms.
Both these natural types have the same general activity.
• Vitamin K3 or menadione is a synthetic product, which is an alkylated form of vitamin K2.
Sources
• Excellent sources are cabbage, cauliflower, spinach and other green vegetables.
• Good sources include tomatoes, cheese, dairy products, meat, egg yolk, etc.
• The vitamin is also synthesized by microorganisms in the intestinal tract.
Absorption, Transport and Storage
The naturally occurring vitamin K derivatives are absorbed only in the presence of bile
salts, like other lipids. It is transported to the liver in the form of chylomicrons, where it is
stored.
Menadione (synthetic vitamin K), being water soluble, is absorbed even in the absence of
bile salt, passing directly into the hepatic portal vein.
Functions of Vitamin K

• Vitamin K plays an important role in blood coagulation. Vitamin K is required for the
activation of blood clotting factors, prothrombin (II), factor VII, IX and X. These blood
clotting proteins are synthesized in liver in inactive form, and are converted to active form
by vitamin K dependent carboxylation reaction. In this, vitamin K dependent carboxylase
enzyme adds the extra carboxy group at χ-carbon of glutamic acid residues of inactive blood
clotting factors.

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• Vitamin K is also required for the carboxylation of glutamic acid residues of osteocalcin, a
Ca2+ binding protein present in bone.
Nutritional Requirements
The suggested intake for adults is 70–140 µg/day.
Deficiency Manifestation
• Vitamin K deficiency is associated with hemorrhagic disease. In vitamin K
deficiency, clotting time of blood is increased. Uncontrolled hemorrhages occur on
minor injuries as a result of reduction in prothrombin and other clotting factors.
• Vitamin K is widely distributed in nature and its production by the intestinal
microflora ensures that dietary deficiency does not occur. Vitamin K deficiency,
however, is found in:
– Patients with liver disease and biliary obstruction. Biliary obstruction inhibits the
entry of bile salts to the intestine.
– In newborn infants, because the placenta does not pass the vitamin to the fetus
efficiently, and the gut is sterile immediately after birth.
– Following antibiotic therapy that sterilizes the gut.
– In fat malabsorption, that impairs absorption of vitamin K.
Hypervitaminosis K
Excessive doses of vitamin K produce a hemolytic anemia (due to increased breakdown of
RBCs) and jaundice (in infants).

7. Sodium and potassium:

Sodium
Sodium is the major cation of extracellular fluids.
Dietary food sources
Table salt (NaCl), salty foods, animal foods, milk and some vegetables.
Recommended dietary allowance per day
• 1–5gm per day
Absorption and excretion
Sodium readily absorbed from the gut and is excreted from the body via urine. There is
normally little loss of sodium occur through skin (sweat) and in the feces. Urinary excretion
of sodium is regulated by aldosterone, which increases sodium reabsorption in kidney.
Metabolic functions
- It maintains the osmotic pressure and water balance.
- It is a constituent of buffer and involved in the maintenance of acid-base balance.
- It maintains muscle and nerve irritability at the proper level.
- Sodium is involved in cell membrane permeability.
- Sodium is required for intestinal absorption of glucose, galactose and amino acids.
Plasma Sodium
The plasma concentration of sodium is 135-145 mEq/ L. Whereas blood cell (intracellular)
contain only about 35 mEq/L.
Clinical Conditions Related to Plasma Sodium Level Alterations
Hypernatremia
Hypernatremia is an increase in serum sodium concentration above the normal range of 135
– 145 mEq/L.
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Causes of hypernatremia
• Water depletion, may arise from a decreased intake or excessive loss with normal sodium
content, e.g. diabetes insipidus.
• Water and sodium depletion, if more water than sodium is lost, e.g. diabetes mellitus
(osmotic diuresis), excessive sweating or diarrhea in children
• Excessive sodium intake or retention in the ECF due to excessive aldosterone secretion,
e.g. Cohn’s syndrome and in Cushing’s syndrome.
Symptoms of hypernatremia
It is due to water loss, then the symptoms are therefore those of dehydration and if it is
due to excess salt gain, leads to hypertension and edema.
Hyponatremia
It is a significant fall in serum sodium concentration below the normal range 135 to 145
mEq/L.
Causes of hyponatremia
• Retention of water: Retention of water dilutes the constituents of the extracellular
space causing hyponatremia, e.g. in heart failure, liver disease, nephrotic syndrome,
renal failure, syndrome of inappropriate ADH secretion (SIADH).
• Loss of sodium: Such losses may be from gastro- intestinal tract, e.g. vomiting,
diarrhea, or in urine. Urinary loss may be due to aldosterone deficiency (Addison’s
disease).
Symptoms of hyponatremia are constant thirst, muscle cramps, nausea, vomiting,
abdominal cramps, weakness and lethargy.

Potassium
Potassium is the main intracellular cation. About 98% of total body potassium is in cells
(150–160 mEq/L), only 2% in the ECF (3.5–5 mEq/L).
Dietary food sources
Vegetables, fruits, whole grain, meat, milk, legumes and tender coconut water.
Recommended dietary allowance per day
• 2–5 gm.
Absorption
Potassium is absorbed readily by passive diffusion from gastrointestinal tract.
Excretion
• Potassium excretion occurs through three primary routes, the gastrointestinal tract,
the skin and the urine. Under normal conditions, loss of potassium through
gastrointestinal tract and skin is very small. The major means of K+ excretion is by
the kidney.
• When sodium is reabsorbed by distal tubule cations (e.g. K+ or H+) in the cell move
into the lumen to balance the charge. Thus during the sodium reabsorption there is
an obligatory loss of potassium.
Serum potassium
The concentration of potassium in serum is around 3.5–5 mEq/L. Serum potassium
concentration does not vary appreciably in response to water loss or retention.
Metabolic functions

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- Potassium maintains the intracellular osmotic pressure, water balance and acid-base
balance.
- It influences activity of cardiac and skeletal muscle.
- Several glycolytic enzymes need potassium for their formation.
- Potassium is required for transmission of nerve impulses.
- Nuclear activity and protein synthesis are dependent on potassium.
Clinical Conditions Related to Plasma Potassium Level Alterations
Hyperkalemia
Hyperkalemia is a clinical condition associated with elevated plasma potassium above the
normal range (3.5–5 mEq/L).
Causes of hyperkalemia
• Renal failure: The kidney may not be able to excrete a potassium load when GFR is very
low.
• Mineralocorticoid deficiency: For example, in Addison’s disease.
• Cell damage: For example, in trauma and malignancy.
Symptoms of hyperkalemia
First manifestation is cardiac arrest, changes in electro- cardiogram, cardiac arrhythmia,
muscle weakness which may be preceded by parasthesia (abnormal tingling sensation).
Hypokalemia (low plasma concentration)
Causes of hypokalemia
• Gastrointestinal losses: Potassium may be lost from the intestine due to vomiting,
diarrhea.
• Renal losses: Due to renal disease, administration of diuretics.
Symptoms of hypokalemia
Muscular weakness, tachycardia, electrocardiographic (ECG) changes (flattering of ECG
waves), lethargy, and confusion.

8.Selenium:
Dietary food sources
Liver, kidney, seafoods and meat are good sources of selenium. Grains have a variable
content depending on the region where they are grown.
Recommended dietary allowance per day
50–200 µg for normal adults.
Functions
• Selenium functions as an antioxidant along with vitamin E.
• Selenium is a constituent of glutathione peroxidase. Glutathione peroxidase has a cellular
antioxidant function, that protects cell membrane, against oxidative damage by H2O2 and a
variety of hydroperoxides.
• Selenium, as a constituent of glutathione peroxidase is important in preventing lipid
peroxidation and protecting cells against superoxide (O2-) and some other free radicals.
• Selenium also is a constituent of iodothyronine deiodinase, the enzyme that converts
thyroxine to triiodothyronine.
Absorption and excretion

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The principal dietary forms of selenium selenocysteine and selenomethionine are absorbed
from gastrointestinal tract. Selenium homeostasis is achieved by regulation of its excretion
via urine.
Deficiency manifestations
Selenium deficiency has been associated in some areas of China with Keshan disease, a
cardiomyopathy, that primarily affects children and women of child bearing age. Its most
common symptoms include dizziness, loss of appetite, nausea, abnormal
electrocardiograms, and congestive heart failure.
Selenium toxicity (selenosis)
Excessive selenium intake results in alkali disease, characterized by loss of hair and nails,
skin lesions, liver and neuromuscular disorders that are usually fatal.

9.Copper and Zinc:

Copper (Cu)
A 70 kg human adult body contains approximately 80 mg of copper. It is present in all
tissues. The highest concentrations are found in liver and kidney, with significant amount in
cardiac and skeletal muscle and in bone.
Dietary food sources
Shellfish, liver, kidneys, egg yolk and some legumes are rich in copper.
Recommended dietary allowance per day
2–3 mg.
Functions
• Copper is an essential constituent of many enzymes including:
– Ceruloplasmin (ferroxidase)
– Cytochrome oxidase
– Superoxide dismutase
– Dopamine β-hydroxylase
– Tyrosinase
– Tryptophan dioxygenase
– Lysyl oxidase.
• Copper plays an important role in iron absorption. Ceruloplasmin, the major copper
containing protein in plasma has ferroxidase activity that oxidizes ferrous ion to
ferric state before its binding to transferrin (tranport form of iron).
• Copper is required for the synthesis of hemoglobin. Copper is a constituent of ALA
synthase enzyme required for heme synthesis.
• Being a constituent of enzyme tyrosinase, copper is required for synthesis of
melanin pigment.
• Copper is required for the synthesis of collagen and elastin. Lysyl oxidase, a copper
containing enzyme converts certain lysine residues to allysine needed in the
formation of collagen and elastin.
Absorption and excretion
About 10% of the average daily dietary copper is absorbed mainly from the duodenum.
Absorbed copper is transported to the liver bound to albumin and exported to peripheral
tissues mainly (about 90%) bound to ceruloplasmin and to a lesser extent (10%) to albumin.
The main route of excretion of copper is in the bile into the gut.
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Plasma copper
Normal plasma concentrations are usually between 100 to 200 mg/dl of which 90% is
bound to ceruloplasmin.
Deficiency manifestation
Signs of copper deficiency include:
• Neutropenia (decreased number of neutrophils) and hypochromic anemia in the
early stages.
• Osteoporosis and various bone and joint abnormalities, due to impairment in copper-
dependent cross-linking of bone collagen and connective tissue.
• Decreased pigmentation of skin due to depressed copper dependent tyrosinase
activity, which is required in the biosynthesis of skin pigment melanine.
• In the later stages neurological abnormalities probably caused by depressed
cytochrome oxidase activity.
Inborn errors of copper metabolism
There are two inborn errors of copper metabolism:
1. Menkes syndrome
2. Wilson’s disease.
Menkes syndrome or Kinky-hair disease
It is very rare, fatal, X-linked recessive disorder. The genetic defect is in absorption of
copper from intestine. Both serum copper and ceruloplasmin and liver copper content are
low. Clinical manifestations occur early in life and include:
• Kinky or twisted brittle hair (steely) due to loss of copper catalyzed disulfide bond
formation.
• Depigmentation of the skin and hair.
• Mental retardation.
Wilson’s disease
• Wilson's disease is an inborn error of copper metabolism. It is an autosomal recessive
disorder in which excessive accumulation of copper occurs in tissues.
The possible causes are:
• An impairment in binding capacity of copper to ceruloplasmin or inability of liver to
synthesize ceruloplasmin or both.
• An impairment in excretion of copper in bile.
Symptoms
• Accumulation of copper in liver, brain, kidney and eyes leading to copper toxicosis.
• Excessive deposition of copper in brain and liver leads to neurological symptoms and
liver damage leading to cirrhosis.
• Copper deposition in kidney leads to renal tubular damage and those in cornea form
yellow or brown ring around the cornea, known as Kayser-Fleisher (KF) rings.
• The disease is also characterized by low levels of copper and ceruloplasmin in plasma
with increased excretion of copper in urine.
Treatment
The excess copper is removed from the body by treatment with penicillamine.

Zinc (Zn)

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Total zinc content of the adult body is about 2 gm. In blood, RBCs contain very high
concentration of zinc as compared to plasma.
Dietary food sources
Meat, liver, seafoods, and eggs are good sources. Milk including breast milk also is a good
source of zinc. The colostrum is an especially rich source.
Recommended dietary allowance per day
15 mg per day for adults with an additional 5 mg during pregnancy and lactation.
Functions
• Zinc is a constituent of a number of enzymes. For example,
– Carbonic anhydrase
– Alkaline phosphatase
– DNA and RNA-polymerases
– Porphobilinogen (PBG) synthase of heme synthesis.
• Because it is required by many of the enzymes needed for DNA and RNA synthesis,
zinc is necessary for the growth and division of cells.
• Zinc is an important element in wound healing as it is a necessary factor in the
biosynthesis and integrity of connective tissue.
• Zinc stabilizes structure of protein and nucleic acids.
• Zinc is required for the secretion and storage of insulin from the β-cells of pancreas.
• Gustin, a Zn containing protein present in saliva is required for the development and
functioning of taste buds. Therefore, zinc deficiency leads to loss of taste acuity.
Absorption and excretion
Approximately 20–30% of ingested dietary zinc is absorbed in small intestine. It is
transported in blood plasma mostly by albumin and α2-macroglobulin. Zinc is excreted in
urine, bile, in pancreatic fluid and in milk in lactating mothers.
Deficiency manifestation
Zinc deficiency has many causes, but malnutrition and malabsorption are the most common.
Clinical symptoms of zinc deficiency include:
• Growth failure
• Hair loss
• Anemia
• Loss of taste sensation
• Impaired spermatogenesis
• Neuropsychiatric symptoms.
Acrodermatitis enteropathica: A rare inherited disorder of zinc metabolism is due to an
inherited defect in zinc absorption that causes low plasma zinc concentration and reduced
total body content of zinc, it is manifested in infancy as skin rash.

10. Normal level of Sodium, Potassium, calcium, and phosphorus in blood:

Sodium: 135-145 mEq/ L
Potassium: 3.5–5 mEq/L
Calcium: 8.5 - 10.5 mg/dl
Phosphorus: 2.5 - 4.5 mg/dl

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11. Balanced diet:
A balanced diet is defined as one which contains a variety of foods in such quantities and
proportions that the need for energy, amino acids, vitamins, minerals, fats, carbohydrate and
other nutrients is adequately met for maintaining health, vitality and general well-being and
also makes a small provision for extra nutrients to withstand short duration of illness.

12. Reducing property of sugar:

Reducing sugars are those that can reduce ions due to the presence of free aldehyde and
ketone groups. All monosaccharides are reducing sugar as they are they have OH group
attached to their anomeric carbon. It forms the brick red precipitate with Benedict's reagent.
It has the capacity to reduce copper ions of Benedict's reagent

13. Homopolysaccharides / Homoglycans:

When a polysaccharide is made up of several units of one and the same type of
monosaccharide unit only, it is called homopolysaccharide.
Examples : Starch, Dextrin, Glycogen, cellulose, Inulin

14. Reducing Disaccharides:

15. Insulin:
Structure of Insulin
i. Insulin is a protein hormone with 2 poly
peptide chains. The A chain has 21 amino acids
and B chain has 30 amino acids.
ii. These two chains are joined together by two
interchain disulphide bonds. There is also an
intrachain disulphide link in A chain between
6th and 11th amino acids.
Biosynthesis of Insulin
i. Insulin is synthesised and secreted by the
beta- cells of the islets of Langerhans of
pancreas.
ii. Insulin is synthesised as a larger precursor
polypeptide chain, proinsulin with 86 amino
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acids. This is then cleaved by a protease. Thus C-peptide or connecting peptide with 33
amino acids is removed.
iii. Insulin with 51 amino acids is thus formed. Insulin and C-peptide are synthesised and
secreted in equimolar quantities.
Factors Increasing Insulin Secretion
i. Glucose: Glucose is the major stimulant of insulin secretion. As blood glucose level
increases, the insulin secretion also correspondingly increases.
The beta cells have GluT2 receptors, which act as the sensors of blood sugar level.
ii. Gastrointestinal hormones: Insulin secretion is enhanced by secretin, pancreozymin and
gastrin. After taking food, these hormones are increased.

16. Ketosis:
i. Normally the rate of synthesis of ketone bodies by the liver is such that they can be
easily metabolized by the extrahepatic tissues. Hence the blood level of ketone bodies
is less than 1 mg/ dl and only traces are excreted in urine (not detectable by usual
tests).
ii. But when the rate of synthesis exceeds the ability of extrahepatic tissues to utilize
them, there will be accumulation of ketone bodies in blood.
iii. This leads to ketonemia, excretion in urine (ketonuria) and smell of acetone in
breath. All these three together constitute the condition known as ketosis.
A. Causes for Ketosis
1. Diabetes mellitus: Untreated diabetes mellitus is the most common cause for ketosis.
Even though glucose is in plenty, the deficiency of insulin causes accelerated lipolysis and
more fatty acids are released into circulation.
2. Starvation: In starvation, the dietary supply of glucose is decreased. The increased rate
of lipolysis is to provide alternate source of fuel. The excess acetyl CoA is converted to
ketone bodies. The high glucagon favours ketogenesis. The brain derives 75% of energy
from ketone bodies under conditions of fasting.
3. Hyperemesis in early pregnancy
B. Regulation of Ketogenesis
i. During starvation and diabetes mellitus, the blood level of glucagon is increased.
Glucagon inhibits glycolysis, activates gluconeogenesis, activates lipolysis, and stimulates
ketogenesis.
ii. Insulin has the opposite effect; it favours glycolysis, inhibits gluconeogenesis, depresses
lipolysis, and decreases ketogenesis.

17.Fatty liver:
Fatty liver is the excessive accumulation of fat primarily neutral fat, triacylglycerol in the
liver. Fats mainly stored in adipose tissue. Liver is not a storage organ. It contains about 5%
fat. In pathological conditions, this may go up to 25–30% and is known as fatty liver or fatty
infiltration of liver.
When accumulation of lipid in the liver becomes chronic, fibrotic changes occur in cells
which may finally lead to cirrhosis and impairment of liver function.
Causes of Fatty Liver

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Fatty liver may occur due to:
1. Overproduction of triacylglycerol in liver.
2. Impaired synthesis of VLDL.
• Overproduction of triacylglycerol: Fatty liver is associated with increased level of
plasma free fatty acids from the diet (high fat diet) or from the adipose tissue during
starvation, diabetes mellitus and alcoholism. The increasing amounts of fatty acids are taken
up by the liver and esterified to triacylglycerol. VLDL produced in liver carries this
triacylglycerol from liver to the peripheral tissues. But the production of VLDL does not
keep pace with the formation of triacylglycerol, allowing triacylglycerol to accumulate in
liver.
• Impaired synthesis of VLDL: Impairement in the biosynthesis of VLDL, in turn, impairs
the transport of triacylglycerol from liver, thus allowing triacylglycerol to accumulate in the
liver. The defect in the synthesis of VLDL may be due to:
1. A block in apolipoprotein synthesis
2. Defect in the synthesis of phospholipids that are found in lipoproteins.
3. A failure in the formation mechanism of lipoprotein itself from lipid and apoprotein.
Factors that Cause Fatty Liver
1. High fat diet: Due to increased supply of free fatty acids from the diet, capacity of liver
for lipoprotein formation is outweighed.
2. Starvation or uncontrolled diabetes mellitus or insulin insufficiency: Due to increased
mobilization of free fatty acids from adipose tissue.
3. Alcoholism: Due to increased hepatic triacylglycerol synthesis and decreased fatty acid
oxidation.
4. Dietary deficiency of:
A. Lipotropic factors: Deficiency of lipotropic factors like choline, betaine, methionine,
lecithin may cause fatty liver. Choline is required for the formation of phospholipid
lecithin, which in turn, is an essential component of lipoprotein. Betain and
methionine possessing methyl groups can be used to synthesize choline.
B. Essential fatty acids: Essential fatty acids are required for the formation of
phospholipid. A deficiency of essential fatty acids leads to decreased formation of
phospholipids.
C. Essential amino acids: Essential amino acids are required for the formation of
apolipoprotein and lipotropic factor choline.
D. Vitamin E and selenium: Deficiency of vitamin E or selenium enhances the hepatic
necrosis. They have protective effect against fatty liver.
E. Protein deficiency: For example, in kwashiorkor, deficiency of protein impairs
formation of apolipoprotein.
F. Vitamin deficiency: Deficiency of pyridoxine and pantothenic acid decrease the
availability of ATP, needed for protein biosynthesis.
5. High cholesterol diet: Excess amount of cholesterol in diet competes for essential fatty
acids for esterification.
6. Use of certain chemicals: For example, puromycin, chloroform, carbon tetrachloride, lead
and arsenic inhibit protein biosynthesis and impair formation of
apolipoprotein.

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18. Lipotropic factor:
• The substances that prevent the accumulation of fat in the liver are known as lipotropic
factors. Dietary deficiency of these factors can result in fatty liver. The various lipotropic
agents are:
– choline
– methionine
– betaine, etc.
• Choline is the principal lipotropic factor, and other lipotropic agents act by producing
choline in the body, e.g. betaine and methionine possessing methyl groups are donated to
ethanolamine to form choline.
• Choline is required for the formation of phospholipid, lecithin, which in turn, is an
essential component of lipoprotein. And formation of lipoprotein is important in the
disposal of triacylglycerol.
• Vitamin B12 and folic acid are also able to produce lipotropic effect, as these are involved
in the formation of methionine from homocysteine.
• Casein and other proteins also possess lipotropic activity.

19. Function of tRNA and mRNA:

Function of tRNA
tRNA carries amino acids in an activated form to the ribosome for the protein synthesis.
Messenger RNA or mRNA
i. It acts as a messenger of the information in the gene in DNA to the protein
synthesizing machinery in cytoplasm. It carries the message to be translated to a
protein.
ii. The template strand of DNA is transcribed into a single stranded mRNA. This is
accomplished by the DNA dependent RNA polymerase.
iii. The mRNA is a complementary copy of the template strand of the DNA.
iv. However, thymine is not present in RNA; instead uracil will be incorporated.

20. Disorders of purine metabolism:

• The catabolism of the purines, adenine and guanine produces uric acid. At physiological
pH, uric acid is mostly ionized and present in plasma as sodium urate.
• An elevated serum urate concentration is known as hyperuricemia. Uric acid and urate
are relatively insoluble molecules which readily precipitate out of aqueous solutions such
as urine or synovial fluid. The consequence of this is the condition, gout.
• The average normal blood serum level of uric acid is 4 to 7 mg per 100 ml.
Gout
Gout is a metabolic disorder associated with an elevated level of uric acid in the serum. The
increased serum uric acid is due to either increased formation of uric acid or its decreased
renal excretion. Whatever be the cause, gout is associated with hyperuricemia but
hyperuricemia is not always associated with gout.
Classification of gout
1. Primary gout
2. Secondary gout
Primary gout
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• Primary gout is an inborn error of metabolism due to overproduction of uric acid. In
primary gout, increased level of uric acid is associated with increased synthesis of purine
nucleotides. Increased synthesis of purine nucleotides is caused by defective enzymes of
purine nucleotide biosynthesis, such as:
– PRPP synthetase
– PRPP glutamyl amidotransferase
– HGPRTase
– Glucose-6-phosphatase
• Symptoms of primary gout
• Patients with primary gout often show deposition of urate as tophi (clusters of
urate crystals) in soft tissues that affects the joints and leads to painful
arthritis.
• The kidneys are also affected, since excess urate is also deposited in the
kidney tubules and leads to renal failure.
Secondary Hyperuricemia
Increased production of uric acid may be due to enhanced turnover rate of nucleic acids
as seen in rapidly growing malignant tissues, e.g. leukemias, lymphomas, polycythemia.
Clinical Findings of Gout
Gouty attacks may be precipitated by high purine diet and increased intake of alcohol.
Often the patients have a few drinks, go to sleep symptomless, but are awakened during the
early hours of morning by excruciating joint pains. The typical gouty arthritis affects the
first metatarsophalangeal joint (big toe), but other joints may also be affected. The joints are
extremely painful. Synovial fluid will show urate crystals.
Treatment Policies in Gout
Reduce dietary purine intake and restrict alcohol. Reduce urate production by allopurinol,
which has structural similarity with hypoxanthine. Allopurinol is a competitive inhibitor of
xanthine oxidase thereby decreasing the formation of uric acid. Xanthine and hypoxanthine
are more soluble and so are excreted more easily.
Lesch-Nyhan Syndrome
It is an X-linked inherited disorder of purine metabolism. Incidence is 1:10,000 males.
There is deficiency of HGPRTase. So, the rate of salvage pathway is decreased resulting in
accumulation of PRPP and decreased level of inhibitory purine nucleotides. The disease is
characterized by self-mutilation, mental retardation, excessive uric acid and nephrolithiasis.
Symptoms:
• Hyperuricemia
• Gout
• Urinary tract stones
• The neurological symptoms or mental retardation
• Spasticity (resistance to the passive movement of a limb)
• Self-mutilation (self painful, destructive behavior of biting of fingers and lips).
Treatment
Allopurinol reduces uric acid formation but does not alleviate the neurologic symptoms.
Xanthinuria

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Deficiency of the enzyme, xanthine oxidase, due to either genetic defect or severe liver
damage results in hypouricemia and increased urinary excretion of xanthine and
hypoxanthine.
Xanthine lithiasis (formation of stones) and secondary renal damage may occur in severe
xanthine oxidase deficiency.

21. Phenyl Ketonuria:

• It is an inborn error of phenylalanine metabolism, associated with the inability to convert
phenyl- alanine to tyrosine.
• The phenylketonuria is inherited in an autosomal recessive manner. The incidence of
phenylketonuria is about 1 in 20,000 newborns.
• In phenylketonuria, there is an accumulation of phenylalanine in tissues and blood and
results in its increased excretion in urine.
• Since phenylketonuric patients cannot convert phenylalanine to tyrosine, by normal
pathway, some minor pathway of phenylalanine becomes prominent in phenylketonurics
and accumulation of toxic metabolites of phenylalanine such as, phenylpyruvate,
phenylacetate, phenyl- lactate and phenylacetyl glutamine occurs.
• The disease acquired its name (PKU) from the high levels of the keto acid,
phenylpyruvate in urine. Almost all untreated phenylketonurics are severely mentally
retarded.
• Untreated phenylketonuria is life threatening, half are dead by age 20 and three quarters
by age 30.

22. Alkaptonuria:
Cause
This inherited metabolic disorder is due to defect in the enzyme homogentisate oxidase,
that catalyzes oxidation of homogentisate. As a result, the homogentisate accumulates in
blood and body tissues and is excreted in large amounts in urine.
Treatment
Since alkaptonuria is not considered life threatening, this condition is not treated. Later in
life, the symptoms of arthritis may be treated but the condition itself is not.
Diagnosis
The urine sample of patients of alkaptonuria turns dark on standing in air. The urine gives
positive test with ferric chloride and silver nitrate due to reducing activity of
homogentisate.

23. Synthesis of glucose from amino acid:

• The synthesis of glucose from noncarbohydrate precursors is called gluconeogenesis
• The glucogenic amino acids are transaminated to TCA cycle intermediates so that they
form oxaloacetate or pyruvate.
• Alanine released from the muscle is the major substrate for gluconeogenesis
• Glucose - alanine cycle: Alanine is transported to liver, transaminated to pyruvate and
converted to glucose. This glucose may again enter the glycolytic pathway to form
pyruvate, which in turn, can be transaminated to alanine. This glucose-alanine cycle is of

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 primary importance in conditions of starvation. Thus net transfer of alanine from muscle
to liver and corresponding transfer of glucose (energy) from liver to muscle is effected.

24. Essential fatty acids:

- Fatty acids, that are required for optimal health and cannot be synthesized by the body
and should be supplied in the diet are called essential fatty acids.
- They are polyunsaturated fatty acids, namely linoleic acid and linolenic acid.
Arachidonic acid can be synthesized from linoleic acid. Therefore, in deficiency of
linoleic acid, arachidonic acid also becomes essential fatty acids.
- Humans lack the enzymes to introduce double bonds at carbon atoms beyond C9 in the
fatty acid chain. Hence, humans cannot synthesize linoleic acid and linolenic acid having
double bonds beyond C9. And thus, linoleic and linolenic are the essential fatty acids.
Functions of Essential Fatty Acids (EFA)
- Synthesis of Eicosanoids
Linoleic acid and linolenic acid supplied by the diet are the precursors for the synthesis of a
variety of other unsaturated fatty acids. Arachidonic acid, a fatty acid derived from linoleic
acid is an essential precursor of eicosanoids, which include:
• Prostaglandins • Thromboxanes • Prostacyclin • Leukotrienes.
- Maintenance of Structural Integrity
EFAs are required for membrane structure and function. These fatty acids are important
constituents of phosphoipids in cell membrane and help to maintain the structural integrity
of the membrane.
- Development of Retina and Brain
Docosahexaenoic acid (DHA: ω-3), which is synthesized from linolenic acid is particularly
needed for development of the brain and retina during the neonatal period.
- Antiatherogenic Effect
Essential fatty acids increase esterification and excretion of cholesterol, thereby lowering
the serum cholesterol level. Thus, essential fatty acids help to prevent the atherosclerosis.
Essential Fatty Acid Deficiency
• Deficiency of EFAs is characterized by scaly skin, eczema (in children), loss of hair
and poor wound healing.
• Impaired lipid transport and fatty liver may occur due to deficiency of EFAs.
• EFAs deficiency decreases efficiency of biological oxidation.

25. How is tyrosine produced in the body? Specialised products formed from Tyrosine:

Tyrosine serves as a precursor for following

several biologically important compounds.
1. Catecholamines
– Dopamine
– Norepinephrine
– Epinephrine
2. Melanin pigment
3. Thyroxine

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26. Classify amino acids based on nutritional importance:
On the basis of nutritional requirement, amino acids are classified into two groups:
i. Essential or indispensable amino acids
ii. Nonessential or dispensable amino acids.
Essential amino acids:
Essential amino acids cannot be synthesized by the body and must, therefore, be essentially
supplied through the diet. Ten amino acids, essential for humans include:
• Phenylalanine • Valine
• Threonine • Tryptophan
• Isoleucine • Methionine
• Histidine • Arginine
• Lysine • Leucine.
The mnemonics often used by students are PVT. TIM. HALL or L.VITTHAL (MP).
Among the ten essential amino acids; arginine and histidine are known as semi-essential
amino acids since these amino acids are synthesized partially in human body.
Nonessential amino acids
Nonessential amino acids can be synthesized in human body and are not required in diet,
• Glycine • Proline
• Serine • Glutamic acid
• Glutamine • Alanine
• Tyrosine • Cysteine
• Aspartic acid • Aspargine.

27. Sulfur containing amino acids

Amino acids having sulfur in the side chain, e.g.
• Cysteine
• Methionine.

28. Heparin:
It is an anticoagulant widely used when taking blood in vitro for clinical studies. It is also
used in vivo in suspected thromboembolic conditions to prevent intravascular coagulation. It
contains sulphated glucosamine.

29. Prostaglandins and its clinical signi cance:

• Prostaglandins are a group of 20-carbon compounds derived from arachidonic acid.
• They derive their name from the tissue in which they were first recognized (the
prostate gland) but they are now known to be present in almost all tissues.
Classification of prostaglandins
• By convention, prostaglandins are abbreviated as PG.
• They are classified into groups designated by a capital letter (A, B, C, D, E, F, G, H
and I) depending on the substituents on the cyclopentane ring.

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 • These are subclassified by a subscript number 1, 2, or 3 corresponding to the number
of double bonds in the side chains but not in the cyclopentane ring.
• Sixteen naturally occurring prostaglandins have been described but only seven are
found commonly throughout the body. These are PGE1, PGE2, PGF1α,
PGF2α, PGG2, PGH2, PGI2.
• Prostaglandins are not stored, instead the precursor C20 arochidonic acids are stored
in tissues.
Functions:
- Smooth muscle contraction and relaxation: For
example, in pregnancy PGF2α are produced in response to oxytocin and act to promote
uterine contraction. Because of this effect, they have been used to terminate unwanted
pregnancies. PGE2 are involved in relaxation of bronchial smooth muscle.
- Inflammatory response: PGs are involved in inflammatory response causing pain,
edema, swelling and prolonged erythema (abnormal flushing of skin) by increasing
capillary permeability.
– Platelet aggregation: Prostaglandins have an effect on platelet aggregation. PGE2
promote aggregation and are thus, involved in the blood clotting.
– Regulation of Blood pressure: PGE2 decrease blood pressure. It can lower systemic
arterial pressure through their vasodilator effect.
– Body temperature: Prostaglandins elevate body temperature producing fever and cause
inflammation, resulting in pain.
– Gastric secretion: PGE2 suppress gastric secretion.
– PGs are involved in Na+ and water retention bykidney tubules.

30. Inhibitors of oxidative phosphorylation:

31. Serum cholesterol level and biological important compounds derived from it:
Serum level:
Cholesterol serves as the precursor for a variety of biologically important products,
including:
1. Steroid hormones: Cholesterol is the precursor of the five steroid hormones, e.g.
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 i. Progesterones
ii. Glucocorticoids
iii. Mineralocorticoids
iv. Androgens (male sex hormones)
v. Estrogen (female sex hormones).
2. Bile acids: Bile acids, derived from cholesterol, act as a detergent in the intestine,
emulsifying dietary fats to make them readily accessible to digestive enzyme lipase.
3. Vitamin D: It is derived from cholesterol and is essential in calcium and phosphate
metabolism.

32. What are Eicosanoids? Give an example.

Prostaglandins and the related compounds thromboxanes and leukotriens, are
collectively known as eicosanoids.
Eicosanoids are synthesized from arachidonic acid. A polyunsaturated fatty acid containing
20-carbon atoms from which they take their general name

33. Explain suicide inhibition of Enzyme with an example.

• These compounds are relatively unreactive until they bind to the active site of a
specific enzyme.
• On binding to the active site of the enzyme they carry out the first few catalytic
activities of the normal enzyme reaction.
• Instead of being transformed into a normal product, however, the inhibitor is
converted to a very reactive compound that combines irreversibly with the enzyme
leading to its irreversible inhibition.
• The enzyme literally commits suicide. These are also called mechanism based
inactivation because they utilize the normal enzyme reaction mechanism to
inactivate the enzyme.
• These inhibitors act as drugs for example
Penicillin
• Penicillin irreversibly inactivates an essential bacterial enzyme glycopeptidyl
transpeptidase involved in the formation of bacterial cell wall.
Aspirin
• Aspirin inactivates an enzyme cyclo-oxygenase which catalyzes the first reaction in the
biosynthesis of prostaglandins from arachidonic acid.

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34. Name two enzymes that are elevated in Myocardial infarction

35. Dietary bers example:

Beans, peas, lentils

36.Substances level elevated in Renal diseases and their normal values.

Creatinine clearance test:
• The normal value of urea clearance is 75 ml/minute.
• Urea clearance between 40-70 ml/min indicates mild impairment, between 20-40 ml/
min indicates moderate impairment and below 20 ml/min
indicates severe impairment of renal function.
Blood analysis:
• An impaired glomerular filtration results in retention of urea and creatinine, which
causes in elevation of blood urea (normal range 20-40 mg/dl) and creatinine (normal
range 0.5 to 1.5 mg/dl). An increase of these end products in the blood is called
azotemia.
Test for protein in urea:
• When glomeruli are damaged in diseased conditions, they become more premeable
and plasma proteins may appear in urine and the condition is known as proteinuria.
• Excretion of albumin more than 300 mg/day is indicative of significant damage to the
glomerular membrane.
• Excretion of albumin in the range 30-300 mg/day is termed microalbuminuria.

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