Citric Acid Cycle

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A Citric Acid Cycle Schematic
A Citric Acid Cycle Schematic

The Citric Acid Cycle is a key metabolic pathway that connects carbohydrate, fat, and protein metabolism!!! See also [1].

The Citric Acid Cycle (tricarboxylic acid cycle) is a series of enzyme catalyzed reactions which are critical in cellular respiration. Under oxidative conditions, pyruvate continues to be metabolized through the tricarboxylic acid cycle. In this cycle, Acetyl-CoA, a byproduct of glycolysis, along with various cofactors, are broken down into carbon dioxide, water, and energy in the form of GTP and NADH.

Pyruvate decarboxylation or pyruvate oxidation, also known as the link reaction (or oxidative decarboxylation of pyruvate), is the conversion of pyruvate into Acetyl-CoA by the enzyme complex pyruvate dehydrogenase complex (see Pyruvate dehydrogenase).

The multienzyme complex together catalyzes five distinct reactions in the conversion of pyruvate to Acetyl-CoA. The overall result is described by the following reaction:

Pyruvate + CoA + NAD+ ==> Acetyl-CoA + CO2 + NADH

However, pyruvate dehydrogenase (E1) is responsible for only the first two of the five reactions. The first of these is the decarboxylation of pyruvate and coupling of thiamine pyrophosphate (TPP) to form hydroxyethyl-TPP.

Pyruvate + TPP ==> Hydroxyethyl-TPP + CO2

Step 0 / 10 - Aldol condensation - Citrate synthase

4C oxaloacetate to a 6C molecule citrate

Step 1 - Dehydration - Aconitase

6C Citrate => 6C cis-Aconitate

Step 2 - Hydration - Aconitase

6C cis-Aconitate => 6C Isocitrate

Step 3 - Oxidation - Isocitrate dehydrogenase

6C Isocitrate => 6C Oxalosuccinate

Step 4 - Decarboxylation - Isocitrate dehydrogenase

6C Oxalosuccinate => 5C α-Ketoglutarate

The α-ketoglutarate family of amino acid synthesis (synthesis of glutamate, glutamine, proline and arginine) begins with α-ketoglutarate, an intermediate in the Citric Acid Cycle. See Alpha-Ketoglutarates: glutamate, glutamine, proline, arginine

Step 5 - Oxidative decarboxylation - α-Ketoglutarate dehydrogenase (2-Oxoglutarate Dehydrogenase)

5C α-Ketoglutarate => Succinyl-CoA 4C chain (CoA excluded)

Step 6 - Substrate-level phosphorylation - Succinyl-CoA synthetase

Succinyl-CoA => Succinate

The succinyl-CoA formed during Beta oxidation can also enter the Citric Acid Cycle in this step.

Step 7 - Oxidation - Succinate dehydrogenase

Succinate => Fumarate

Step 8 - Hydration - Fumarase

Fumarate => L-Malate

Step 9 - Oxidation - Malate dehydrogenase

L-Malate => oxaloacetate

Oxaloacetate takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis (Oxaloacetate/aspartate: lysine, asparagine, methionine, threonine, and isoleucine), fatty acid synthesis.

Step 10 / 0 - Aldol condensation - Citrate synthase

4C oxaloacetate to a 6C molecule citrate

To view automatically seeded indices concerning Citric Acid Cycle See:


See also:


Open conformation of citrate synthase dimer complex with citrate (PDB code 1cts) and closed conformation of citrate synthase dimer complex with citrate and CoA (PDB code 2cts)

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

Alexander Berchansky, David Canner, Ann Taylor, Wayne Decatur, Jaime Prilusky

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