Published by Patrick Mutisya · 14 days ago
The Krebs cycle is the central pathway of aerobic respiration. It occurs in the mitochondrial matrix and
processes the acetyl‑CoA derived from glycolysis and pyruvate oxidation. The key chemical changes in each
turn of the cycle are:
For one molecule of acetyl‑CoA entering the cycle, the net reaction can be written as:
\$\$\text{Acetyl‑CoA} + 3\,\text{NAD}^+ + \text{FAD} + \text{GDP} + \text{P}i + \text{H}2\text{O}
\;\longrightarrow\; 2\,\text{CO}2 + 3\,\text{NADH} + \text{FADH}2 + \text{GTP} + \text{CoA‑SH}\$\$
| Step | Substrate | Product(s) | Enzyme | Co‑enzyme (Reduced) |
|---|---|---|---|---|
| 1. Citrate formation | Acetyl‑CoA + Oxaloacetate | Citrate + CoA‑SH | Citrate synthase | – |
| 2. Isomerisation | Citrate | Isocitrate | Aconitase | – |
| 3. First decarboxylation & dehydrogenation | Isocitrate | α‑Ketoglutarate + CO₂ + NADH | Isocitrate dehydrogenase | NADH |
| 4. Second decarboxylation & dehydrogenation | α‑Ketoglutarate | Succinyl‑CoA + CO₂ + NADH | α‑Ketoglutarate dehydrogenase complex | NADH |
| 5. Substrate‑level phosphorylation | Succinyl‑CoA | Succinate + GTP + CoA‑SH | Succinyl‑CoA synthetase | – |
| 6. Dehydrogenation | Succinate | Fumarate + FADH₂ | Succinate dehydrogenase | FADH₂ |
| 7. Hydration | Fumarate | Malate | Fumarase | – |
| 8. Dehydrogenation | Malate | Oxaloacetate + NADH | Malate dehydrogenase | NADH |
Steps 3 and 4 each remove a carbon atom from the substrate as carbon dioxide. This shortens the carbon
chain and releases energy that is captured by the reduction of NAD⁺ to NADH.
During dehydrogenation, hydrogen atoms (as H⁺ and electrons) are transferred from the substrate to the
co‑enzymes:
These reduced co‑enzymes then donate their electrons to the electron transport chain, driving ATP synthesis.
Four molecules of NAD⁺ and one molecule of FAD are reduced per turn of the cycle, giving a total of
three NADH, one FADH₂, and one GTP (≈ ATP) directly from the cycle. The high‑energy electrons carried by
NADH and FADH₂ are the main source of ATP in oxidative phosphorylation.
the point of CO₂ release, and where NAD⁺/FAD are reduced.
Both processes are essential for extracting the chemical energy stored in carbon bonds:
allowing the remaining carbon skeleton to be fully oxidised.
carriers that feed the electron transport chain.
The Krebs cycle is a series of eight enzyme‑catalysed reactions that achieve three fundamental
transformations:
These transformations provide the reduced co‑enzymes (NADH, FADH₂) that drive the majority of ATP
production in aerobic respiration.