Jawaharlal Nehru Technological University Hyderabad B.Pharmacy I BIOCHEMISTRY Previous Question Paper (June-2022 - R17)

The Citric Acid Cycle, also known as the Krebs cycle or TCA cycle, is the central metabolic pathway occurring in the mitochondrial matrix that oxidizes acetyl-CoA to carbon dioxide, generating high-energy electron carriers for the electron transport chain.

The pathway proceeds through the following enzymatic steps:

1. Condensation of acetyl-CoA (2C) with oxaloacetate (4C) by citrate synthase to form citrate (6C).
2. Isomerization of citrate to isocitrate via aconitase.
3. Oxidative decarboxylation of isocitrate to alpha-ketoglutarate by isocitrate dehydrogenase, releasing CO₂ and producing NADH.
4. Oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA by the alpha-ketoglutarate dehydrogenase complex, releasing CO₂ and producing NADH.
5. Conversion of succinyl-CoA to succinate by succinyl-CoA synthetase, coupled with substrate-level phosphorylation to produce GTP (or ATP).
6. Oxidation of succinate to fumarate by succinate dehydrogenase, producing FADH₂.
7. Hydration of fumarate to malate by fumarase.
8. Oxidation of malate to oxaloacetate by malate dehydrogenase, producing another NADH, regenerating the cycle.

The net reaction for one turn of the cycle is:

The energetics of the cycle are derived from the oxidation of the acetyl group. Each turn yields 3 NADH (approx. 7.5 ATP), 1 FADH₂ (approx. 1.5 ATP), and 1 GTP (equivalent to 1 ATP), totaling approximately 10 ATP per acetyl-CoA molecule oxidized.

The significance of the cycle includes:

• It is the final common pathway for the oxidation of carbohydrates, lipids, and amino acids.
• It provides essential precursors for biosynthetic pathways, such as succinyl-CoA for heme synthesis and alpha-ketoglutarate for amino acid synthesis.
• It generates the majority of NADH and FADH₂ required for oxidative phosphorylation, serving as the primary source of cellular energy.