TCA cycle 2024

Tricarboxylic Acid (TCA) Cycle Overview

  • Also known as: Kreb's cycle or citric acid cycle.

  • Key Components:

    • Pyruvate (C2)

    • Acetyl CoA

    • CO2 production

  • Location: Mitochondria of the cells.

TCA Cycle Key Facts

  • Entry: C2 fragment enters in the form of Acetyl CoA.

  • Gas Products: Two CO2 molecules are released during the cycle.

  • Carboxylic Acids: All intermediates are carboxylic acids, with names ending in "ate" except for succinyl CoA.

  • O2 Requirement: Molecular oxygen (O2) is not directly involved in the cycle.

  • Hydrogen Atoms: Four hydrogen atoms are removed (three as NADH, one as FADH2).

  • ATP Production: Only one ATP (or GTP, readily converted to ATP) is produced from each cycle.

TCA Cycle Dynamics

  • Energy Coupling: The cycle turns due to the sequential coupling of reactions. One reaction with a large negative ΔG drives various reversible reactions.

  • Reversible Reactions: Some reactions in the cycle have ΔG ≈ 0 which allows adaptability.

  • CO2 Utilization: CO2 produced during the cycle cannot be taken back for acetyl CoA re-entry.

TCA Cycle Steps

Step One: Formation of Citrate

  • Process: A condensation (aldol) followed by hydrolysis.

  • Enzyme: Citrate synthase.

  • Reactants: Acetyl CoA combines with oxaloacetate to form citrate.

Step Two: Isomerization

  • Process: A dehydration followed by hydration.

  • Enzyme: Aconitase.

  • Transformation: Citrate is converted to cis-aconitate and then isocitrate.

Step Three: Oxidation

  • Process: A dehydrogenation followed by decarboxylation.

  • Enzyme: Isocitrate dehydrogenase.

  • Products: Produces NADH and CO2 from isocitrate to α-ketoglutarate.

Step Four: Further Oxidation

  • Process: A dehydrogenation followed by decarboxylation.

  • Enzyme: α-ketoglutarate dehydrogenase complex.

  • Products: α-ketoglutarate converts to succinyl CoA, producing NADH and CO2.

Step Five: Substrate-Level Phosphorylation

  • Process: GDP is phosphorylated to GTP.

  • Enzyme: Succinyl CoA synthetase.

  • Transformation: Succinyl CoA is converted to succinate.

Step Six: Oxidation to Fumarate

  • Process: Oxidation (FAD reduced to FADH2).

  • Enzyme: Succinate dehydrogenase.

  • Transformation: Succinate is converted to fumarate.

Step Seven: Hydration

  • Process: A straightforward hydration.

  • Enzyme: Fumarase.

  • Transformation: Fumarate is converted to malate.

Step Eight: Final Oxidation

  • Process: An unfavorable oxidation.

  • Enzyme: Malate dehydrogenase.

  • Products: Malate is converted back to oxaloacetate, producing NADH.

Regulation of the TCA Cycle

  • Key regulators: ATP, ADP, acetyl CoA, and NADH; they influence the cycle's activity.

  • Anaplerotic reactions: These reactions help maintain the levels of cycle intermediates, ensuring the cycle continues efficiently.

Summary

  • The TCA cycle is essential for energy production, converting pyruvate to acetyl CoA is irreversible.

  • The cycle has eight steps where energy transfer is crucial, and it’s tightly regulated through various mechanisms to meet the metabolic demands.