The citric acid cycle (TCA cycle) is an essential metabolic pathway at the end of the degradation of all nutrients that yield acetyl-CoA, including carbohydrates, lipids, ketogenic amino acids, and alcohol. Acetyl-CoA is a product of glycolysis (at high glucose levels) or beta-oxidation (at low glucose levels) and the first substrate of the TCA cycle. Over the course of the cycle, acetyl-CoA is oxidized to CO2 in 8 steps, and the energy that this generates is stored in FADH2, NADH+H+, and GTP. FADH2, NADH+H+ are then oxidized in the (electron transport chain), which ends in ATP synthesis. The intermediates of the TCA cycle are precursors for both anabolic and catabolic processes.
- Description: : metabolic pathway that oxidizes acetyl-CoA to CO2 and generates one molecule GTP and the electron carriers NADH + H+ and FADH2(pathway is also known as Krebs cycle).
- Site: mitochondria
- Steps: acetyl-CoA + oxaloacetate → citrate → isocitrate → α-ketoglutarate → succinyl-CoA → succinate → fumarate → malate → oxaloacetate
Citrate Is Krebs' Starting Substrate For Making Oxaloacetate
- Citrate synthase: oxaloacetate → citrate; requires CoA (vitamin B5 pantothenic acid)
- Isocitrate dehydrogenase: Isocitrate → α-ketoglutarate
- α-Ketoglutarate dehydrogenase: α-ketoglutarate → succinyl-CoA
- Yield: 1 acetyl-CoA yields 3 NADH+H+ + 1 FADH2 + 1 GTP + 2 CO2 (one glucose molecule yields 2 acetyl-CoA) → 7.5 ATP (from 3 NADH+H+)+ 1.5 ATP (from 1 FADH2) + 1 ATP (from 1 GTP); = 10 ATP
Each C2 unit is completely oxidized to CO2 and H2O. Oxaloacetate is recycled for the next TCA cycle.
- Occurs at several sites
|Citrate synthase (irreversible)|| |
| || |
|Isocitrate dehydrogenase (irreversible)|| |
α-Ketoglutarate dehydrogenase (irreversible)
|Succinyl-CoA synthetase|| || |
|Succinate dehydrogenase|| |
|Fumarase|| || |
|Malate dehydrogenase|| || |
Metabolic pathway of
|Anabolic precursor||Catabolic precursor|
Inhibition of the TCA cycle results in ketone body production.
- ↑ Acetyl-CoA → ketogenesis (acetoacetyl-CoA → HMG-CoA → acetoacetate → β-hydroxybutyrate)