JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD B. Pharmacy I Year BIOCHEMISTRY Previous Question Paper (September/October-2021 - R17)

The HMP shunt (Hexose Monophosphate pathway), also known as the Pentose Phosphate Pathway, is an alternative route for glucose oxidation that occurs in the cytosol. It consists of two phases: the oxidative phase and the non-oxidative phase.

1. Oxidative Phase: Glucose-6-phosphate is converted to 6-phosphogluconolactone by glucose-6-phosphate dehydrogenase (G6PD), producing NADPH. Further oxidation and decarboxylation yield ribulose-5-phosphate and a second molecule of NADPH.
2. Non-oxidative Phase: Ribulose-5-phosphate undergoes reversible interconversions catalyzed by transketolase and transaldolase to produce ribose-5-phosphate and glycolytic intermediates like fructose-6-phosphate and glyceraldehyde-3-phosphate.

The significance of the HMP shunt includes: 1) Providing NADPH for fatty acid and steroid biosynthesis and for maintaining reduced glutathione in erythrocytes to protect against oxidative damage. 2) Supplying ribose-5-phosphate for nucleotide and nucleic acid synthesis. 3) Enabling the metabolism of dietary pentoses.

Glycogen metabolism involves two primary pathways: Glycogenesis (synthesis) and Glycogenolysis (degradation).

1. Glycogenesis: Occurs when glucose levels are high. Glucose is converted to glucose-6-phosphate, then glucose-1-phosphate, and activated to UDP-glucose. Glycogen synthase adds these units to a glycogen primer, while branching enzymes create alpha-1,6-linkages.
2. Glycogenolysis: Occurs during fasting or exercise. Glycogen phosphorylase cleaves alpha-1,4-glycosidic bonds to release glucose-1-phosphate, while debranching enzymes handle the alpha-1,6-branch points.

Glycogen Storage Diseases (GSDs) are inherited metabolic disorders caused by enzyme deficiencies in these pathways, leading to abnormal glycogen accumulation or structure. Examples include: Von Gierke's disease (Type I, glucose-6-phosphatase deficiency causing severe fasting hypoglycemia), Pompe's disease (Type II, lysosomal alpha-1,4-glucosidase deficiency leading to cardiomegaly), and McArdle's disease (Type V, muscle phosphorylase deficiency causing muscle cramps and weakness).