In the Krebs cycle, how is the oxidation of acetyl groups coupled to the reduction of hydrogen carriers, and how does this release carbon dioxide?

Sourav PanNovember 9, 2024

Answered

In the Krebs cycle (also known as the citric acid cycle or tricarboxylic acid cycle), the oxidation of acetyl groups from acetyl-CoA is coupled to the reduction of hydrogen carriers such as NAD+ and FAD, leading to the release of carbon dioxide (CO₂). Here’s a detailed explanation of how these processes occur:

Overview of the Krebs Cycle

The Krebs cycle takes place in the mitochondrial matrix and consists of a series of enzymatic reactions that oxidize acetyl-CoA to produce energy-rich molecules and release CO₂ as a waste product. Each turn of the cycle processes one acetyl group, and since two acetyl-CoA molecules are generated from one glucose molecule, the cycle runs twice for each glucose.

Key Steps in the Krebs Cycle

1. Formation of Citrate:
   • Acetyl-CoA (a two-carbon molecule) combines with oxaloacetate (a four-carbon molecule) to form citrate (a six-carbon molecule).
   • Enzyme: Citrate synthase catalyzes this reaction, releasing coenzyme A (CoA).
2. Isomerization:
   • Citrate is converted into its isomer, isocitrate, through a rearrangement process.
   • Enzyme: Aconitase facilitates this transformation.
3. First Oxidation and Decarboxylation:
   • Isocitrate is oxidized to α-ketoglutarate (a five-carbon molecule), during which NAD+ is reduced to NADH.
   • This reaction releases one molecule of CO₂.
   • Enzyme: Isocitrate dehydrogenase catalyzes this step.
4. Second Oxidation and Decarboxylation:
   • α-Ketoglutarate undergoes further oxidation to succinyl-CoA (a four-carbon molecule), resulting in another reduction of NAD+ to NADH and the release of a second CO₂ molecule.
   • Enzyme: α-Ketoglutarate dehydrogenase catalyzes this reaction.
5. Substrate-Level Phosphorylation:
   • Succinyl-CoA is converted to succinate, producing ATP (or GTP) through substrate-level phosphorylation.
   • Enzyme: Succinyl-CoA synthetase catalyzes this conversion.
6. Further Oxidation:
   • Succinate is oxidized to fumarate, reducing FAD to FADH₂ in the process.
   • Enzyme: Succinate dehydrogenase catalyzes this reaction.
7. Hydration:
   • Fumarate is hydrated to form malate.
   • Enzyme: Fumarase facilitates this addition of water.
8. Final Oxidation:
   • Malate is oxidized back to oxaloacetate, reducing another NAD+ to NADH.
   • This step regenerates oxaloacetate, allowing the cycle to continue.
   • Enzyme: Malate dehydrogenase catalyzes this final reaction.

Summary of Products

For each turn of the Krebs cycle:

• 2 CO₂ molecules are released as waste products.
• 3 NADH molecules are produced (from isocitrate to α-ketoglutarate, α-ketoglutarate to succinyl-CoA, and malate to oxaloacetate).
• 1 FADH₂ molecule is produced (from succinate to fumarate).
• 1 ATP (or GTP) is produced from succinyl-CoA.

Coupling of Oxidation and Reduction

The oxidation of acetyl groups in the Krebs cycle is coupled with the reduction of NAD+ and FAD at multiple points:

• As acetyl groups are oxidized during the conversion of citrate through various intermediates back to oxaloacetate, high-energy electrons are transferred to NAD+ and FAD, forming NADH and FADH₂. These reduced cofactors carry electrons to the electron transport chain for further ATP production through oxidative phosphorylation.