Paper I- August 2011

I. ESSAY

1. Describe in detail TCA cycle and the energetic. Justify why TCA cycle is called

an amphibolic cycle. [ Apr 2001, Aug 2006 SN, Aug 2004 essay]

The citric acid cycle (Krebs cycle, tricarboxylic acid cycle) is a series of reactions in mitochondria that oxidize acetyl residues (as acetyl-CoA) and reduce coenzymes that upon reoxidation are linked to the formation of ATP.

Fig TCA cycle

The citric acid cycle is not only a pathway for oxidation of two-carbon units—it is also a major pathway for interconversion of metabolites arising from transamination and deamination of amino acids. It also provides the substrates for amino acid synthesis by transamination, as well as for gluconeogenesis and fatty acid synthesis. Because it functions in both oxidative and synthetic processes, it is amphibolic

2. Describe in detail the components and chemiosmotic theory of ETC.[Apr

2001, sep 2002, feb 2006 SN]

• In ETC, the electrons are transferred from NADH to a chain of electron carriers.

• All components of ETC are situated in inner membrane of mitochondria. They are

• Complex I - NADH dehydrogenase, also called NADH Coenzyme Q reductase.

• Complex II - Succinate - Coenzyme Q reductase.

• Complex III - Coenzyme Q - cytochrome c reductase.

• Complex IV - Cytochrome c oxidase.

Complex V (ATP synthase complex)

Salient features:

• Complexes I, III, and IV are proton pumps.

• Complex II is part of the Krebs cycle and does not pump protons

• Complex IV is the terminus of the electron transfer chain, consuming oxygen and making

water.

• ATP Yield: NADH = 3 ATP (entry at Complex I)

FADH2 = 2 ATP (entry at Complex II)

The coupling of oxidation with phosphorylation is termed oxidative phosphorylation.

Peter Mitchell in 1961 proposed this theory to explain oxidative phosphorylation

Oxidative phosphorylation is comprised of the following processes

1) Oxidation of reducing equivalents (NADH and FADH2)

2) Electron transfer through 3 protein assemblies (Complex I, III, and IV) to O2

3) Transport of H+ into inter membrane space.

4) Transport of H+ into the mitochondrial matrix

5) Synthesis of ATP.

Fig ETC

II Write short notes on (5 marks)

1. Role of Niacin as coenzyme

Nicotinamide adenine dinucleotide (NAD+)

Nicotinamide adenine dinucleotide phosphate (NADP+).

• NAD+/NADH takes part in oxidation reduction reactions.

• NADPH mostly takes part in reductive biosynthesis.

NAD+ Dependent Enzymes

• Lactate dehydrogenase (Lactate to Pyruvate)

• Glyceraldehyde 3 phosphate dehydrogenase

NADPH Generating Reactions

• Glucose 6 phosphate dehydrogenase

• 6-phospho gluconate dehydrogenase

NADPH Utilizing Reactions

• Fatty acid synthase complex

• HMG CoA to Mevolanate

• Met hemoglobin to Hemoglobin

• Phenylalanine to Tyrosine

• Folate to Dihydrofolate to Tetrahydrofolate

2. Classification of hyperlipidemias and their importance

3. Sphingolipidoses

4. Biochemical role of vit C [Aug 2005 essay, Aug 2008 SN]

Very essential for bone formation

Iron metabolism

Tryptophan & Tyrosine metabolism

Antioxidant

Met-hemoglobin to hemoglobin

Immune functions

Needed for Folic acid metabolism

Collagen synthesis, Cataract prevention, Cancer prevention,

Cellular respiration, Cholesterol metabolism

5. Cori’s cycle and Alanine cycle [Feb 2007 Essay]

Definition: Transferring lactate from tissue to liver and synthesis of glucose is known as cori’s

cycle.

Effects

It rescues lactate for further use (gluconeogenesis)

It counteracts lactic acidosis.

It is of less importance in starvation but important in more normal situations

esp in certain cells such as matured RBC, medulla, retina which are lacking

mitochondria and virtually anaerobic.

unlike alanine cycle it does not consume any energy

Cori’s cycle

Fig Cori cycle

Glucose Alanine cycle:

• Alanine synthesized in muscle and transported to liver where it is converted

to glucose.

• Muscle protein-------- alanine-------- pyruvate---- glucose

• It occurs in

1. Starvation

2. Uncontrolled diabetes

Lactate

2Pyruvate

Glucos

e

Glucose

glycolysis

2ATP

6ATP

Gluconeogenesis

LIVER

Alanine2-NH2

2NAD+

2NADH+ H+

2Alanine

2Pyruvate

Glucose

2-NH2

Urea

Urea

Kidney

Glucose

Alanine

MUSCLE

CELL

Glucose Alanine cycle

6. HDL cycle [Aug 2010 SN]

Fig HDL cycle

7. Glycogenolysis [Sep 2002 , Feb 2006 Essay]

Glycogen phosphorylasecatalyzesthe phosphorylyticcleavage by inorganic phosphate (phosphorylysis)

of the 1→4 linkages of glycogen to yield glucose1-phosphate. The terminal glucosyl residues fromthe

outermost chains of the glycogen molecule are removedsequentially until approximately four

glucoseresidues remain on either side of a 1→6 branch

Another enzymeglucantransferase transfers a trisaccharide unit from onebranch to the other, exposing

the 1→6 branch point.Hydrolysis of the 1→6 linkages requires the debranching

enzyme.Hydrolysis of the 1→6 linkages requires the debranchingenzyme. Further phosphorylase action

can then proceed. The combined action of phosphorylaseand these other enzymes leads to the

complete breakdownof glycogen.

The reaction catalyzed by phosphoglucomutaseis reversible, so that glucose 6-phosphatecan be formed

from glucose 1-phosphate. In liver andkidney, but not in muscle, there is a specific enzyme,glucose-6-

phosphatase, that hydrolyzes glucose6-phosphate, yielding glucose that is exported, leadingto an

increase in the blood glucose concentration.

8.Isomerism in carbohydrates

Sugars Exhibit Various Forms of Isomerism Glucose, with four asymmetric carbon atoms, can form 16 isomers.

(1) D and L isomerism: The designation of a sugar isomer as the D form or of its mirror image as the L form

(2) Pyranose and furanose ring structures: The stable ring structures of monosaccharides are similar to the ring structures of either pyran (a six-membered ring) or furan (a five-membered ring). For glucose in solution, more than 99% is in the pyranose form. (3) Alpha and beta anomers: The ring structure of an aldose is a hemiacetal, since it is formed by combination of an aldehyde and an alcohol group. Similarly, the ring structure of a ketose is a hemiketal. Crystalline glucose is α-D-glucopyranose. The cyclic structure is retained in solution, but isomerism occurs about position 1, the carbonyl or anomeric carbon atom, to give a mixture of α-glucopyranose (38%) and β-glucopyranose (62%). Less than 0.3% is represented by α and β anomers of glucofuranose. (4) Epimers: Isomers differing as a result of variations in configuration of the OH and H on carbon atoms 2, 3, and 4 of glucose are known as epimers. Biologically, the most important epimers of glucose are mannose and galactose, formed by epimerization at carbons 2 and 4, respectively (5) Aldose-ketose isomerism: Fructose has the same molecular formula as glucose but differs in its structural formula, since there is a potential keto group in position 2, the anomeric carbon of fructose whereas there is a potential aldehyde group in position 1, the anomeric carbon of glucose

Fig Isomerism in monosaccharides

9. Balanced diet [ Aug 2007 SN]

1. The diet should be simple, locally available, palatable and digestible.

2. Adequate protein content with essential amino acids should be supplied. This is achieved by

cereal pulses mixture with additional animal proteins.

3. Calorie intake should be correct and should balance energy expenditure.

4. Special care should be taken to see that adequate quantity of calcium and iron are obtained

from the diet.

5. Should provide adequate roughage.

6. Cereal pulses ratio is maintained at 5:1

7. Daily requirement of protein is 60 g, fat – 45 g, calories- 2000 k cal, ca-400 mg, iron -25 g.

8. Diet is divided into 3 meals per day, breakfast, lunch, supper.

9. Balanced diet should contain calories from carbohydrates, protein and fat in the ratio

60:20:20

10. Fructose intolerance

Lack of hepatic fructokinase causes essential fructosuria, and absence of hepatic aldolase B,

which cleaves fructose 1-phosphate, leads to hereditary fructose intolerance.

Diets low in fructose, sorbitol, and sucrose are beneficial for both conditions. One consequence

of hereditary fructose intolerance and of another condition due to fructose-1,6-bisphosphatase

deficiency is fructose-induced hypoglycemia despite the presence of high glycogen reserves.

The accumulation of fructose 1-phosphate and fructose 1,6-bisphosphate allosterically inhibits

the activity of liver phosphorylase. The sequestration of inorganic phosphate also leads to

depletion of ATP and hyperuricemia.

III. Short Answer (1 mark)

1. Markers of lysosomes and mitochondria

Organelles Marker Enzyme

Lysosomes Cathepsin

Mitochondria ATP synthase

2. Flurosis [ [Aug 2008 – 2 marks]

i. Fluoride is the trace element. It helps to prevent tooth decay.

ii. The safe limit is 1 ppm in water ( parts per million)

iii. 1 ppm = 1 g of fluoride in millions of water, this is equal to 1 mg/1000 ml)

iv. Fluoride level more than 20 ppm is toxic , leading to alternate areas of osteoporosis and

osteosclerosis with brittle bones. This is called fluorosis.

3. Role of Apo C II

It activates lipoprotein lipase.

4. Define metalloenzymes with 2 eg.

NAD, FAD

5. Pulmonary surfactant

6. Iodine no.

It is defined as the number of grams of iodine taken up by 100 grams of fat. It is an index of the

degree of unsaturation and is directly proportional to the content of unsaturated fatty acids.

Higher the iodine number, higher is the degree of unsaturation.

Food substances Iodine no.

Butter 28

Sunflower oil 30

7. What is the function lipoprotein lipase?

Its function is to hydrolyses TGL present in chylomicrons into fatty acids and glycerol. It is

located in the endothelial layer of capillaries of adipose tissue, muscles and heart. It is not

present in liver.

8. Structure of lecithin

Lecithin is phosphotidyl choline.

9. Net protein utilization

Suppose 127 mg of protein A was consumed by a rat and 4 mg is recovered in feces

and 24 mg is seen in urine.

Then

Amount ingested = 127 mg

Amount absorbed = 127-4 =123 mg

Amount retained = 123-24 = 99 mg. Formula for calculating Biological value (BV)

Therefore BV = (99/123)*100 =81%

Net protein utilization (NPU):

NPU = (retained nitrogen/ intake of nitrogen )* 100

NPU of protein A = (99/127)*100 = 78%

NPU of protein B = (4.5/100)*100 = 4.5%

Thus NPU is a better index than BV.

10. Chondroitin sulphate –structure [Feb 2009 SN]

Consist of repeating units of L-iduronic acid & N-acetyl galactosamine. It is important

structural component of cartilage.

Fig Chondoitin sulphate

11. Double reciprocal plot.[ April 2011 SN]

Sometimes the determination of eznzye activity is needs very high substrate concentration,

which is impractical. A linear form of the Michaelis-Menten equation circumvents this difficulty

and permits Vmax and Km to be extrapolated from initial velocity data obtained at less than

saturating concentrations of substrate.

12. ALP as a diagnostic tool.

It is increased in liver disease (jaundice) and bone disorder.

13. What are the different forms of calcium in the blood?

3 forms of calcium in blood:

1. Ionized ca ( active form) – 5 mg/dl.

2. Protein bound Ca - 4 mg/dl.

3. Protein complex with phosphate, HCO3-, Citrate – 1 mg/dl

14. RDA and functions of Iodine

RDA: 150-200 microgram/ day.

Functions:

Only biological role of iodine is; it helps in the formation of Thyroxine and tri iodo thyronine.

15. Why Arachidonic acid is not considered purely as EFA?

Ans. Arachidonic acid can be synthesized in our body, if the essential fatty acids (linoleic and

linolenic acid) are supplied in diet.