Pyruvate decarboxylation

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The Pyruvate decarboxylation reaction links the metabolic pathways glycolysis and the citric acid cycle. This reaction is the conversion of pyruvate, the end product of glycolysis, into acetyl CoA. The pyruvate decarboxylation reaction may be simply referred to as "the transition reaction", "the link reaction", or "the oxidative decarboxylation reaction". In eukaryotes, this reaction is catalyzed by the pyruvate dehydrogenase complex.

This reaction is part of the aerobic respiration pathway.

The pyruvate decarboxylation reaction is not part of either glycolysis or the citric acid cycle. It is, however, often portrayed as part of one or the other for simplicity.

1 Pyruvate decarboxylation reaction
2 Regulation of pyruvate decarboxylation
3 Localisation of pyruvate decarboxylation
4 Post-pyruvate decarboxylation processes
5 See also
6 References

[edit] Pyruvate decarboxylation reaction

pyruvate	pyruvate dehydrogenase complex		acetyl CoA

	CoA + NAD⁺	CO₂ + NADH + H⁺

This reaction is a complex multistep process which involves two cofactors. First the pyruvate is broken down into carbon dioxide and acetaldehyde with a thiamine pyrophosphate (cocarboxylase) cofactor. Then, the acetaldehyde binds to the sulphur molecule on Coenzyme A, forming Acetyl CoA. This step uses an α-lipoate cofactor. The reaction is coupled to the reduction of NAD⁺ to NADH.

Coenzyme A is later released from acetyl CoA, during the citric acid cycle. This recycling of the coenzyme allows pyruvate decarboxylation to recur indefinitely under aerobic respiration.

[edit] Regulation of pyruvate decarboxylation

Escherichia coli pyruvate dehydrogenase. PDB 21EA.

Pyruvate dehydrogenase complex catalyzes this reaction and is regulated by several inhibitors and promoters:

Inhibitors:

Acetyl CoA - its product (negative feedback).
ATP - abundant in cells with low ATP, and so respiration, demand.
NADH - abundant in cells where oxidative phosphorylation cannot keep up with NADH production.

Promoters:

Phosphoenolpyruvate - a late intermediate of active glycolysis.
nucleotide monophosphates - abundant in cells with high ATP demand.

These factors have the overall effect of slowing this reaction when there is either little oxygen, or when the cell has a lot of energy (as characterized by the ratios ATP/ADP, NADH/NAD⁺ and acetyl-CoA/CoASH).

[edit] Localisation of pyruvate decarboxylation

In eukaryotic cells the pyruvate decarboxylation occurs inside the mitochondria, after transport of the substrate, pyruvate, from the cytosol. The transport of pyruvate into the mitochondria is via a transport protein, consuming energy. Passive diffusion of pyruvate into the mitochondria is impossible because it is a polar molecule.

On entry to the mitochondria the pyruvate decarboxylation occurs, producing acetyl CoA. This irreversible reaction traps the acetyl CoA within the the mitochondria (there is no transporter for acetyl CoA). The carbon dioxide produced by this reaction is nonpolar and small, and can diffuse out of the mitochondria and out of the cell.

In prokaryotes, which have no mitochondria, this reaction is either carried out in the cytosol, or not at all.

[edit] Post-pyruvate decarboxylation processes

The acetyl CoA produced by this reaction may go on to a variety of different metabolic pathways. The major usage is the citric acid cycle and aerobic respiration, but acetyl CoA is also a major substrate for lipid and amino acid synthesis. Indirectly, intermediates in the citric acid pathway may also be used for synthesis.

The NADH produced may also be used in several ways. Under aerobic conditions, NADH may be oxidized by the electron transport chain into NAD⁺, renewing this reactant for use in oxidative decarboxylation (this requires oxygen). In anaerobic conditions, NAD⁺ can be regenerated by anaerobic respiration; however, acetyl coA will quickly build up as it is no longer consumed by the stalled citric acid cycle, and this inhibits the forward reaction.

[edit] See also

Cellular Respiration
Aerobic Respiration
Glycolysis → Pyruvate Decarboxylation → Citric Acid Cycle → Oxidative Phosphorylation (Electron Transport Chain + ATP synthase)
Anaerobic Respiration
Glycolysis → Lactic Acid Formation or Ethanol Formation