Question

Please help me with Metabolism 25 marks question. Thank you very much.

(a) The pentose phosphate pathway seems like a biologically wasteful process.

(i) Explain how the pathway might be wasteful compared to other carbon metabolic pathways. (2 marks)

(ii) Explain the importance of the pentose phosphate pathway. (4 marks)

(b) Excessive nitrogen needs to be excreted from the body. Describe the biochemical pathway(s) for nitrogen elimination. (8 marks)

(c) The following are two glycogen molecules from two different individuals, X and Y. The lines represent oligosaccharide chains:

(i) Deduce which individual (X or Y) has a defect in glycogen production. (1 mark)

(ii) Hypothesize which enzyme(s) could be defective in the individual from (i) and explain. (6 marks)

(iii) Explain the consequences of producing a defective glycogen molecule as in the individual from part (i). (4 marks)

Answer 1

A.i) Pentose phosphate pathway is also known as hexose monophosphate shunt. This pathway bypasses the glycolysis step and alternately produce NADPH and pentose sugar. On complete oxidation of these pentose sugar shows that, there is production of a total of 36 ATP. But 1 molecule of ATP is used in formation of glucose to glucose-6-phosphate. So, net production is 35 ATPs. Whereas, in glycolysis and crews cycle, one glucose molecule on complete oxidation can produce a total of 38 ATPs.
'this is the reason, it is thought that HMP shunt is a biologically waste process.

ii) Significance of HMP shunt:

1. Formation of NADPH-
NADPH is produced in this pathway which is used as electron donor in many reductive synthesis in the body. Examples of such reactions where NADPH is used:
• Extramitochondrial de novo fatty acid synthesis,
• In synthesis of cholesterol,
• In synthesis of steroids,
• In conversion of oxidised glutathione G-S-S-G to reduced glutathione G-SH,
• In synthesis of sphingolipids

2. Provision of Pentoses
Provision of pentoses for nucleotide and nucleic acid synthesis; the source of the D-Ribose is the D-ribose-5-P,an intermediate in this pathway.

3. Role in RB Cells Fragility
HMP-shunt in erythrocytes provides NADPH for:
• Reduction of oxidised glutathione (G-S-S-G) to reduced glutathione (2 G-SH) catalysed by the enzyme glutathione reductase.
• Reduced glutathione (G-SH) thus formed in turn removes H2O2 from the erythrocytes in a reaction catalyzed by glutathione peroxidase.
This reaction is important, since accumulation of H2O2 may decrease the life span of RB Cells by increasing the rate of oxidation of Hb to methaemoglobin. An inverse correlation exists between the activity of ‘G-6-PD’ enzyme and the fragility of red cells (Susceptibility to haemolysis).

4. Role in Lens Metabolism-
In studying lens metabolism, it has been observed, at least 10 per cent of Glucose is metabolised by shunt pathway and provides NADPH, which is necessary to convert oxidised glutathione to reduced glutathione, which is necessary for maintenance of lens proteins.
5. Role in Phagocytosis-
Reactions of this pathway are increased manifold in Leucocytes during ‘phagocytosis’. NADPH generated in this pathway is utilised by “NADPH oxidase” in producing Superoxide anions (O2–) for destroying Phagocytosed materials.

6. Role in Tissue Anoxia-
Tissues subjected to extended periods of anoxia develop fatty infiltration.
Explanation: Increased amounts of glucose may be metabolised by way of HMP-shunt, in situations resulting from tissue anoxia. The mechanism involved appears to be that the lack of tissue O2 decreases the metabolism of pyruvate by way of TCA cycle. Inter- mediates of anaerobic glycolysis accumulate resulting in a diversion of G-6-P into HMP-shunt pathway, resulting to increased amount of NADPH (lowering the NADP/NADPH ratio). The excess NADPH is diverted to increased FA synthesis, thus accounting for “fatty infiltration”.