Citric Acid Cycle - Steps

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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