UPSC MainsZOOLOGY-PAPER-II202510 Marks
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Q22.

6.(a)(i) Write down the reactions that produce NADH during Krebs cycle.

How to Approach

To answer this question effectively, I will begin by defining the Krebs cycle and its role in cellular respiration. The main body will detail each specific step within the cycle where NAD+ is reduced to NADH, explicitly stating the substrate and product for each reaction. A table will be used to summarize these reactions for clarity. The conclusion will reiterate the significance of NADH production in energy generation.

Model Answer

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Introduction

The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, is a pivotal metabolic pathway in aerobic respiration, occurring in the mitochondrial matrix of eukaryotic cells. Its primary function is the complete oxidation of acetyl-CoA, derived from carbohydrates, fats, and proteins, to carbon dioxide, generating ATP (or GTP), FADH₂, and crucially, NADH. NADH is a high-energy electron carrier that plays a vital role in the subsequent oxidative phosphorylation, where its electrons are used to drive ATP synthesis, thus making the Krebs cycle an indispensable part of cellular energy production.

Reactions Producing NADH During the Krebs Cycle

The Krebs cycle involves a series of redox, dehydration, hydration, and decarboxylation reactions. For each molecule of acetyl-CoA that enters the cycle, three molecules of NADH are typically produced within the cycle itself. There is also an additional NADH produced during the preparatory step (pyruvate oxidation) that converts pyruvate to acetyl-CoA, which is often considered in conjunction with the Krebs cycle's overall NADH yield from glucose. The three specific steps within the Krebs cycle where NAD⁺ is reduced to NADH are:

1. Isocitrate Dehydrogenase Reaction

This is the first oxidative decarboxylation step in the Krebs cycle. Isocitrate, a six-carbon molecule, is oxidized, and a molecule of carbon dioxide is released. During this process, NAD⁺ acts as an electron acceptor and is reduced to NADH. The product of this reaction is α-ketoglutarate, a five-carbon molecule.

Isocitrate + NAD⁺ → α-Ketoglutarate + CO₂ + NADH + H⁺

2. α-Ketoglutarate Dehydrogenase Complex Reaction

Following the formation of α-ketoglutarate, it undergoes another oxidative decarboxylation. This reaction is catalyzed by the α-ketoglutarate dehydrogenase complex, which is structurally and mechanistically similar to the pyruvate dehydrogenase complex. α-Ketoglutarate is oxidized, another molecule of carbon dioxide is released, and NAD⁺ is reduced to NADH. Coenzyme A (CoA) is simultaneously incorporated, forming succinyl-CoA, a four-carbon molecule with a high-energy thioester bond.

α-Ketoglutarate + NAD⁺ + CoA-SH → Succinyl-CoA + CO₂ + NADH + H⁺

3. Malate Dehydrogenase Reaction

The final reaction that produces NADH in the Krebs cycle involves the oxidation of malate to oxaloacetate. Malate, a four-carbon molecule, is oxidized, and NAD⁺ is reduced to NADH. This regeneration of oxaloacetate is crucial as it allows the cycle to continue by condensing with a new molecule of acetyl-CoA.

Malate + NAD⁺ → Oxaloacetate + NADH + H⁺

These three reactions collectively contribute to the significant production of NADH, which then feeds into the electron transport chain to generate the bulk of cellular ATP.

Summary of NADH Producing Reactions

The following table summarizes the reactions within the Krebs cycle that produce NADH:
Step Number Enzyme Substrate Product NADH Produced
1 Isocitrate Dehydrogenase Isocitrate α-Ketoglutarate 1
2 α-Ketoglutarate Dehydrogenase Complex α-Ketoglutarate Succinyl-CoA 1
3 Malate Dehydrogenase Malate Oxaloacetate 1

It is important to note that an additional molecule of NADH is produced during the oxidative decarboxylation of pyruvate to acetyl-CoA, a reaction that precedes the entry of acetyl-CoA into the Krebs cycle. While not technically part of the cycle itself, it is intimately linked to glucose catabolism.

Conclusion

The production of NADH during the Krebs cycle is a critical aspect of aerobic cellular respiration, underpinning the efficient generation of energy in living organisms. Through three distinct oxidative steps catalyzed by isocitrate dehydrogenase, α-ketoglutarate dehydrogenase complex, and malate dehydrogenase, NAD⁺ is reduced to NADH. Each turn of the cycle yields three NADH molecules, which, along with the NADH from glycolysis and pyruvate oxidation, are essential for driving the electron transport chain and subsequent ATP synthesis via oxidative phosphorylation. This intricate biochemical pathway highlights the fundamental mechanisms by which cells extract and convert energy from nutrients.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Krebs Cycle (Citric Acid Cycle)
A series of biochemical reactions that occur in the mitochondrial matrix of eukaryotic cells, involving the oxidation of acetyl-CoA to carbon dioxide, producing ATP (or GTP), NADH, and FADH₂ as energy carriers.
NADH (Nicotinamide Adenine Dinucleotide Hydride)
A coenzyme that acts as a reducing agent, carrying electrons from various metabolic reactions (like the Krebs cycle) to the electron transport chain, where these electrons are used to generate ATP.

Key Statistics

Approximately 95% of the energy used by aerobic cells in humans is produced through processes involving the Krebs cycle and oxidative phosphorylation.

Source: News-Medical.net (2025)

For each glucose molecule, two turns of the Krebs cycle occur, yielding a total of 6 NADH, 2 FADH₂, and 2 ATP (or GTP) molecules from the cycle itself (excluding glycolysis and pyruvate oxidation).

Source: Khan Academy, News-Medical.net

Examples

Cellular Energy Production

In marathon runners, efficient function of the Krebs cycle and subsequent oxidative phosphorylation is crucial to sustain high levels of ATP production required for prolonged muscle activity. A robust supply of NADH and FADH₂ from the Krebs cycle ensures continuous energy supply.

Metabolic Intermediates for Biosynthesis

Beyond energy production, intermediates of the Krebs cycle, such as α-ketoglutarate and oxaloacetate, serve as precursors for the synthesis of amino acids and other biomolecules. For instance, oxaloacetate can be transaminated to aspartate, an important amino acid.

Frequently Asked Questions

What is the significance of NADH in the context of overall cellular respiration?

NADH is a critical electron carrier. The electrons it carries possess high energy, which is later utilized in the electron transport chain (the final stage of aerobic respiration) to create a proton gradient across the inner mitochondrial membrane. This gradient then drives the synthesis of a large amount of ATP through chemiosmosis.

Does the Krebs cycle directly consume oxygen?

No, the Krebs cycle itself does not directly consume oxygen. However, it is considered an aerobic pathway because the regeneration of NAD⁺ from NADH, which is essential for the cycle to continue, relies on the electron transport chain, which ultimately uses oxygen as the final electron acceptor.

Topics Covered

BiochemistryCellular RespirationKrebs CycleElectron Transport ChainMetabolism