JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD B.Pharmacy I Year BIOCHEMISTRY Previous Question Paper (November/December-2020 - R17)

The Citric Acid Cycle (also known as the Krebs cycle or TCA cycle) is the final common metabolic pathway for the oxidation of carbohydrates, lipids, and proteins. It occurs in the mitochondrial matrix and serves as the primary source of electron donors for the electron transport chain.

The cycle proceeds through the following key steps:

1. Condensation: Acetyl-CoA (2C) condenses with Oxaloacetate (4C) to form Citrate (6C) by the enzyme citrate synthase.
2. Isomerization: Citrate is converted to Isocitrate via the intermediate cis-aconitate by aconitase.
3. First Oxidative Decarboxylation: Isocitrate is oxidized to α-Ketoglutarate by isocitrate dehydrogenase, releasing CO2 and producing NADH.
4. Second Oxidative Decarboxylation: α-Ketoglutarate is converted to Succinyl-CoA by the α-ketoglutarate dehydrogenase complex, releasing CO2 and producing NADH.
5. Substrate-Level Phosphorylation: Succinyl-CoA is converted to Succinate by succinyl-CoA synthetase, coupled with the phosphorylation of GDP to GTP (or ADP to ATP).
6. Dehydrogenation: Succinate is oxidized to Fumarate by succinate dehydrogenase, producing FADH2.
7. Hydration: Fumarate is hydrated to form L-Malate by fumarase.
8. Regeneration: Malate is oxidized back to Oxaloacetate by malate dehydrogenase, producing another molecule of NADH.

The net yield per one molecule of Acetyl-CoA entering the cycle is 3 NADH, 1 FADH2, and 1 GTP (equivalent to 1 ATP). When these reduced coenzymes are oxidized via the electron transport chain, they generate additional ATP through oxidative phosphorylation. Specifically, 3 NADH yield approximately 7.5 ATP (3 x 2.5) and 1 FADH2 yields 1.5 ATP. Including the 1 GTP/ATP produced directly, the total ATP yield per turn of the cycle is 10 ATP.

The Electron Transport Chain (ETC) is a series of protein complexes and electron carriers located in the inner mitochondrial membrane. It is the final stage of aerobic respiration where electrons derived from NADH and FADH2 are transferred through a series of redox reactions to molecular oxygen, ultimately driving the synthesis of ATP through oxidative phosphorylation.

The process involves four major multi-protein complexes:

1. Complex I (NADH Dehydrogenase): Accepts electrons from NADH, transferring them to Coenzyme Q (ubiquinone). This step pumps four protons into the intermembrane space.
2. Complex II (Succinate Dehydrogenase): Part of the citric acid cycle, it accepts electrons from succinate via FADH2 and transfers them to Coenzyme Q. No protons are pumped here.
3. Complex III (Cytochrome bc1 Complex): Transfers electrons from reduced Coenzyme Q to cytochrome c. This step pumps four protons into the intermembrane space.
4. Complex IV (Cytochrome c Oxidase): Transfers electrons from cytochrome c to molecular oxygen, forming water. This step pumps two protons into the intermembrane space.

As electrons move through these complexes, the released energy is used to pump protons from the mitochondrial matrix into the intermembrane space, creating an electrochemical proton gradient (proton-motive force). This gradient is then utilized by ATP Synthase (Complex V), which allows protons to flow back into the matrix, providing the energy required to phosphorylate ADP to ATP. This coupling of electron transport to ATP synthesis is known as oxidative phosphorylation.

The ETC is essential for cellular energy production, and its efficiency is tightly regulated by the availability of oxygen and the ADP/ATP ratio within the cell.