Dalvoy Logo
Dalvoy
UPSC MainsZOOLOGY-PAPER-II201620 Marks
Q21.

Discuss that TCA cycle is the central pathway in the energy metabolism of a cell.

How to Approach

This question requires a detailed understanding of the Tricarboxylic Acid (TCA) cycle, also known as the Krebs cycle or citric acid cycle. The answer should focus on explaining the cycle's central role in cellular energy metabolism, its inputs, outputs, and its connections to other metabolic pathways. Structure the answer by first introducing the TCA cycle, then detailing its steps and significance, and finally highlighting its integration with glycolysis, fatty acid oxidation, and the electron transport chain. Emphasize the cycle’s role in generating reducing equivalents (NADH and FADH2) and precursors for biosynthesis.

Model Answer

0 min read

Introduction

The Tricarboxylic Acid (TCA) cycle, a series of chemical reactions, is universally present in aerobic organisms and represents the final common pathway for the oxidation of carbohydrates, fats, and proteins. Discovered by Hans Krebs in 1937, this cyclical pathway occurs within the mitochondrial matrix in eukaryotes and the cytoplasm in prokaryotes. It’s not merely an energy-generating process; it also provides crucial precursors for various biosynthetic pathways. Understanding the TCA cycle is fundamental to comprehending cellular respiration and overall energy homeostasis. The cycle’s central position allows it to integrate metabolic pathways, making it the cornerstone of cellular energy metabolism.

The TCA Cycle: A Detailed Overview

The TCA cycle is a series of eight enzymatic reactions. It begins with the condensation of acetyl-CoA (a two-carbon molecule) with oxaloacetate (a four-carbon molecule) to form citrate (a six-carbon molecule). The cycle then proceeds through a series of decarboxylation, oxidation, and hydration reactions, ultimately regenerating oxaloacetate to continue the cycle.

Steps of the TCA Cycle

  • Step 1: Condensation of Acetyl-CoA with Oxaloacetate to form Citrate (catalyzed by citrate synthase).
  • Step 2: Isomerization of Citrate to Isocitrate (catalyzed by aconitase).
  • Step 3: Oxidative Decarboxylation of Isocitrate to α-Ketoglutarate (catalyzed by isocitrate dehydrogenase). This step produces the first NADH.
  • Step 4: Oxidative Decarboxylation of α-Ketoglutarate to Succinyl-CoA (catalyzed by α-ketoglutarate dehydrogenase complex). This step produces another NADH.
  • Step 5: Conversion of Succinyl-CoA to Succinate (catalyzed by succinyl-CoA synthetase). This step generates GTP (which can be converted to ATP).
  • Step 6: Oxidation of Succinate to Fumarate (catalyzed by succinate dehydrogenase). This step produces FADH2.
  • Step 7: Hydration of Fumarate to Malate (catalyzed by fumarase).
  • Step 8: Oxidation of Malate to Oxaloacetate (catalyzed by malate dehydrogenase). This step produces another NADH.

Significance of the TCA Cycle

The TCA cycle is central to energy metabolism for several key reasons:

  • ATP Production: While the cycle directly produces only one GTP (equivalent to ATP) per turn, its primary contribution to ATP production is indirect. The cycle generates three NADH and one FADH2 molecules per turn. These reducing equivalents donate electrons to the electron transport chain, leading to the generation of a substantial amount of ATP through oxidative phosphorylation.
  • Biosynthetic Precursors: The TCA cycle intermediates serve as precursors for various biosynthetic pathways. For example:
    • α-Ketoglutarate is a precursor for glutamate and other amino acids.
    • Succinyl-CoA is a precursor for heme synthesis.
    • Oxaloacetate is a precursor for glucose via gluconeogenesis and amino acids.
  • Integration of Metabolic Pathways: The TCA cycle integrates the metabolism of carbohydrates, fats, and proteins.
    • Carbohydrates: Pyruvate, derived from glycolysis, is converted to acetyl-CoA, which enters the TCA cycle.
    • Fats: Fatty acid oxidation produces acetyl-CoA, which also enters the TCA cycle.
    • Proteins: Amino acids can be converted to various TCA cycle intermediates.

Regulation of the TCA Cycle

The TCA cycle is tightly regulated to meet the cell's energy demands. Key regulatory enzymes include:

  • Citrate Synthase: Inhibited by ATP, NADH, succinyl-CoA, and citrate.
  • Isocitrate Dehydrogenase: Activated by ADP and Ca2+, inhibited by ATP and NADH.
  • α-Ketoglutarate Dehydrogenase Complex: Inhibited by succinyl-CoA, NADH, and ATP.
Input Output
Acetyl-CoA CO2
Oxaloacetate NADH (3 molecules)
H2O FADH2 (1 molecule)
NAD+ GTP (1 molecule)
FAD Oxaloacetate (regenerated)

Conclusion

In conclusion, the TCA cycle is undeniably the central pathway in cellular energy metabolism. Its ability to oxidize acetyl-CoA derived from carbohydrates, fats, and proteins, coupled with its generation of reducing equivalents and biosynthetic precursors, makes it indispensable for life. The cycle’s tight regulation ensures that energy production is matched to cellular needs. Further research continues to unravel the intricacies of the TCA cycle and its role in various metabolic disorders, highlighting its continued importance in biomedical science.

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.

Evaluate your handwritten answer in under a minute

Free trial available • Trusted by 1,00,000+ aspirants

Additional Resources

Key Definitions

Acetyl-CoA
Acetyl-CoA is a molecule that serves as a key intermediate in many biochemical reactions. It is formed from pyruvate during glycolysis and fatty acid oxidation and is the primary fuel for the TCA cycle.
Oxidative Phosphorylation
Oxidative phosphorylation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing energy which is used to produce adenosine triphosphate (ATP).

Key Statistics

Approximately 20 ATP molecules are produced per glucose molecule through oxidative phosphorylation, driven by the NADH and FADH2 generated by the TCA cycle and glycolysis. (Based on knowledge cutoff 2023)

Source: Textbook of Biochemistry with Clinical Correlations, 8th Edition

The mitochondrial matrix, where the TCA cycle occurs, occupies approximately 20-25% of the cell volume in highly metabolic tissues like muscle and liver. (Based on knowledge cutoff 2023)

Source: Alberts et al., Molecular Biology of the Cell, 6th edition.

Examples

Beriberi and TCA Cycle

Beriberi, caused by thiamine (Vitamin B1) deficiency, impairs the activity of pyruvate dehydrogenase complex, which converts pyruvate to acetyl-CoA. This disruption hinders the entry of pyruvate into the TCA cycle, leading to energy deficiency and neurological symptoms.

Frequently Asked Questions

▶What happens if the TCA cycle is blocked?

If the TCA cycle is blocked, energy production significantly decreases. Cells rely heavily on glycolysis for ATP, leading to lactic acid accumulation. Biosynthetic pathways are also disrupted due to the lack of TCA cycle intermediates.

Topics Covered

BiologyBiochemistryCellular RespirationMetabolismTCA Cycle
Back to all ZOOLOGY-PAPER-II 2016 questions