Steps
Two carbon atoms are oxidized to CO2, the energy from these reactions being transferred to other metabolic processes by GTP (or ATP), and as electrons in NADH and QH2. The NADH generated in the TCA cycle may later donate its electrons in oxidative phosphorylation to drive ATP synthesis; FADH2 is covalently attached to succinate dehydrogenase, an enzyme functioning both in the TCA cycle and the mitochondrial electron transport chain in oxidative phosphorylation. FADH2, therefore, facilitates transfer of electrons to coenzyme Q, which is the final electron acceptor of the reaction catalyzed by the Succinate:ubiquinone oxidoreductase complex, also acting as an intermediate in the electron transport chain.
The citric acid cycle is continuously supplied with new carbon in the form of acetyl-CoA, entering at step 1 below.
| Substrates | Products | Enzyme | Reaction type | Comment | |
|---|---|---|---|---|---|
| 1 | Oxaloacetate + Acetyl CoA + H2O |
Citrate + CoA-SH |
Citrate synthase | Aldol condensation | irreversible, extends the 4C oxaloacetate to a 6C molecule |
| 2 | Citrate | cis-Aconitate + H2O |
Aconitase | Dehydration | reversible isomerisation |
| 3 | cis-Aconitate + H2O |
Isocitrate | Hydration | ||
| 4 | Isocitrate + NAD+ |
Oxalosuccinate + NADH + H + |
Isocitrate dehydrogenase | Oxidation | generates NADH (equivalent of 2.5 ATP) |
| 5 | Oxalosuccinate | α-Ketoglutarate + CO2 |
Decarboxylation | rate-limiting, irreversible stage, generates a 5C molecule |
|
| 6 | α-Ketoglutarate + NAD+ + CoA-SH |
Succinyl-CoA + NADH + H+ + CO2 |
α-Ketoglutarate dehydrogenase | Oxidative decarboxylation |
irreversible stage, generates NADH (equivalent of 2.5 ATP), regenerates the 4C chain (CoA excluded) |
| 7 | Succinyl-CoA + GDP + Pi |
Succinate + CoA-SH + GTP |
Succinyl-CoA synthetase | substrate-level phosphorylation | or ADP→ATP instead of GDP→GTP, generates 1 ATP or equivalent Condensation reaction of GDP + Pi and hydrolysis of Succinyl-CoA involve the H2O needed for balanced equation. |
| 8 | Succinate + ubiquinone (Q) |
Fumarate + ubiquinol (QH2) |
Succinate dehydrogenase | Oxidation | uses FAD as a prosthetic group (FAD→FADH2 in the first step of the reaction) in the enzyme, generates the equivalent of 1.5 ATP |
| 9 | Fumarate + H2O |
L-Malate | Fumarase | Hydration | |
| 10 | L-Malate + NAD+ |
Oxaloacetate + NADH + H+ |
Malate dehydrogenase | Oxidation | reversible (in fact, equilibrium favors malate), generates NADH (equivalent of 2.5 ATP) |
Mitochondria in animals, including humans, possess two succinyl-CoA synthetases: one that produces GTP from GDP, and another that produces ATP from ADP. Plants have the type that produces ATP (ADP-forming succinyl-CoA synthetase). Several of the enzymes in the cycle may be loosely-associated in a multienzyme protein complex within the mitochondrial matrix.
The GTP that is formed by GDP-forming succinyl-CoA synthetase may be utilized by nucleoside-diphosphate kinase to form ATP (the catalyzed reaction is GTP + ADP → GDP + ATP).
Read more about this topic: Citric Acid Cycle
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