Biochemistry May 2000 Pro Essay Paper (By Pooh)

National University of Singapore
Faculty of Medicine
First Professional MBBS Examination
Structural and Cell Biology Track

Date: 28 April, 2000
Time: 9am - 12pm

This paper constitues 70% of the total final assessment for the academic year.
This paper consists of 6(Six) printed pages.
There are two sections, A and B.
Part A - Attempt all 15 questions. Each question will be marked out of a total of ten (10) marks.
Part B - Answer all 3 questions. Each question will be marked out of a total of thirty marks.

1. a) Outlne why the carbon dioxide-bicarbonate system is an effective physiological buffer. (5 marks)
b) How would obstructive lung disease affect the buffer system? (5 marks)

2. a) List the major structural features of the triple helix of collagen (5 marks)
b) Explain how a lack of vitamin C in the diet can affect its functional stability. (5 marks)

3. <involves diagram>

4. Explain the meaning of the term "DNA fingerprinting" and outline its applications

5. A patient had a mutation that led to the expression of a channel protein allowing movement of monovalent cations through the inner mitochondrial membrane of his muscle mitochondria. He suffered from fatigue, inability of perform strenous exercise without muscle cramps, and a body temperature of 39.4(?) degrees C. Explain the biochemical basis of these symptoms.

6. The consumption of glucose by heart muscle can be measured by artifically circulating blood through an isolated intact heart and measuring the concentration before and after the blood passes through the heart. If the circulating blood is deoxygenated, heart muscle consumes glucose at a steady rate. When oxygen is added in the blood, the rate of glucose consumption drops dramatically, then continues at the new lower rate. Why?

7. Besides its important roles in protein structure/synthesis and in the urea cycle, arginine also has another two important functional roles. What are these?

8. If a volunteer subject consumes pyruvate containing radioactive carbon atoms, is there a possibility that radioactivity will soon be detectable in the following compounds after they have been isolated from his tissues? Give reasons for your answers, but detailed pathways are not required.
a) Testosterone (4m)
b) Oleic acid (3m)
c) Phosphatidyl choline (lecithin) (3)

9. One of the local slimming centres recommends that its obese clients go on a completely fat-free diet, but can replace fat with foods containing carbohydrate (starch and sucrose). Are such clients likely to lose a proportion of their body fat? Explain your answer.

10. Compare X-linkage by meiotic segregation with X-linkage by X-inactivation (Lyonization).

11. Four-year-old John suffers from severe dementia and ataxia. His father came down with similar, although less severe symptoms when he was 30 years old while his grandfather only presented with very mild ataxis when he was in his fifties.
a) What is the term that describes this increase in severity in subsequent generations? (2m)
b) Explain the molecular mechanism for this phenomenon. (8m)

12. Explain the difference between mRNA that has just been transcribed from the eukaryotic genome and mature mRNA ready for protein synthesis.

13. a) State the Law of Independent Assortment. (2m)
b) When does this law hold true, and when does it not? (8m)

14. Briefly outline the ionic basis for the various phases of a nerve action potential.

15. Why does fatigue not occur in cardiac muscle?

Part B
1. Aspirin is frequently used in the management of patients with arterial vascular disease and thromboembolism. In certain circumstances, the use of aspirin results in gastric mucosal damage.
a) Describe briefly the normal microscopic features of a gastric gland. (5m)
b) Briefly describe the normal physiological mechanisms protecting the gastric mucosa against the local acid and enzymatic environment. (10m)

Aspirin is converted to salicylic acid and can be further metabolised to some of the metabolites shown below.
Structural diagram for aspirin breakdown

c) Name the enzymes and the conjugating agents needed for reactions 1 and 2. (4m)
d) Outline the synthesis of the conjugating agents for reactions 1 and 2. (4m)
e) Reaction 3 is catalyzed by an enzyme X.
 i] What is enzyme X? (1m)
 ii] Enzyme X is inducible by certain endogenous as well as exogenous compounds. Explain the term "inducible" (1m)
 iii] What is the general reaction catalysed by enzyme X? (1m)
 iv] This enzyme contains a prosthetic group. Define the term "prosthetic group". What is the prosthetic group in enzyme X and what is its role in the function of enzyme X? (3m)
f)What is the conjugating agent for reaction 4? (1m)

2. The patient was a 12-year-old-girl who has a grossly enlarged abdomen. She had a history of frequent episodes of weakness, sweating, and pallor that were eliminated by eating.
The following are laboratory findings for a fasting blood sample

 PatientNormal Values
Free fatty acids1.60.3-0.8
Total ketone bodies400<30
Total CO21224-30

A liver biopsy specimen was obtained through an abdominal incision. Glycogen content was 11g/100g of liver (normal up to 8g/100g). Hepatic glycogen structure was normal.
The following are results of enzyme assays performed on the liver biopsy tissue.

Enzyme Patient Normal
Glucose-6-phosphatase 22 170-260
Glucose-6-phosphate dehydrogenase 0.07 0.05-0.13
Phosphoglucomutase 27 21-29
Phosphorylase 24 19-25
Fructose 1,6-bisphosphatase 8.4 4-16

Liver biopsy histology
a) Light microscopy of the biopsy is shown above. Identify the structures A to D. (4 marks)
b) What is the normal structure of hepatic glycogen? (4m)
c) In this patient, which other tissues might be expected to accumulate excessive amounts of glycogen? Explain. (4m)
d) Explain the reason for the fasting hypoglycaemic episodes. (6m)
e) To what might be ascribed [i]the elevated free fatty acid, [ii] the elevated ketone bodies, and [iii] the metabolic acidosis? (12m)

3. a) The pedigree shows a family suffering from the "KS" syndrome. From the pedigree, the most likely mode of inheritance of this syndrome is "X-linked". Explain why, indicating which individuals in the pedigree must be assumed to be carriers for the "X-linked" mode of inheritance to be true. (10m)
b) Besides the clinical syndrome of KS, no other information about the disease or the biochemical defect is known. Describe the various steps of the strategy you would adopt to find the gene responsible for this syndrome. (20m)
Family Tree

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