JNTU B.Pharmacy I Year BIOCHEMISTRY Previous Question Paper (July/August -2021 - R17)

The Hexose Monophosphate (HMP) shunt, also known as the Pentose Phosphate Pathway, is a cytosolic metabolic pathway that runs parallel to glycolysis. It primarily generates NADPH for reductive biosynthesis and ribose-5-phosphate for nucleotide synthesis.

The pathway consists of two distinct phases:

• Oxidative Phase (Irreversible): Glucose-6-phosphate is converted to 6-phosphogluconolactone by glucose-6-phosphate dehydrogenase (G6PD), producing NADPH. This is followed by hydrolysis to 6-phosphogluconate and a second oxidative decarboxylation by 6-phosphogluconate dehydrogenase to produce ribulose-5-phosphate and a second molecule of NADPH.
• Non-Oxidative Phase (Reversible): This phase involves a series of sugar-phosphate interconversions catalyzed by transketolase and transaldolase enzymes. These reactions shuffle carbon atoms between 3, 4, 5, 6, and 7-carbon sugars to regenerate glucose-6-phosphate or produce intermediates for glycolysis (fructose-6-phosphate and glyceraldehyde-3-phosphate).

The pathway is regulated primarily by the availability of NADP⁺ and the activity of the rate-limiting enzyme, G6PD, which is inhibited by high levels of NADPH. It is essential in tissues with high biosynthetic activity, such as the liver, adipose tissue, and lactating mammary glands, as well as in erythrocytes for maintaining reduced glutathione levels.

The Citric Acid Cycle, also known as the Krebs cycle or TCA cycle, is the final common pathway for the oxidation of fuel molecules (carbohydrates, fatty acids, and amino acids). It occurs in the mitochondrial matrix and serves as the primary source of energy by generating high-energy electron carriers for the electron transport chain.

The cycle begins with the condensation of Acetyl-CoA (2 carbons) with Oxaloacetate (4 carbons) to form Citrate (6 carbons), catalyzed by citrate synthase. The sequence of reactions is as follows:

• Citrate is isomerized to Isocitrate by aconitase.
• Isocitrate undergoes oxidative decarboxylation to α-Ketoglutarate, releasing CO₂ and producing NADH, catalyzed by isocitrate dehydrogenase.
• α-Ketoglutarate is converted to Succinyl-CoA, releasing CO₂ and producing NADH, via the α-ketoglutarate dehydrogenase complex.
• Succinyl-CoA is converted to Succinate by succinyl-CoA synthetase, coupled with the substrate-level phosphorylation of GDP to GTP (or ADP to ATP).
• Succinate is oxidized to Fumarate by succinate dehydrogenase, producing FADH₂.
• Fumarate is hydrated to Malate by fumarase.
• Malate is oxidized back to Oxaloacetate by malate dehydrogenase, producing another molecule of NADH, completing the cycle.

The net reaction for one turn of the cycle is:

The cycle is amphibolic, meaning it functions in both catabolism (energy production) and anabolism (providing precursors for biosynthesis like amino acids and heme). It is regulated primarily by the energy status of the cell, specifically the ratios of ATP/ADP and NADH/NAD+.