Pyruvate decarboxylation

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". This reaction is catalyzed by the pyruvate dehydrogenase complex.

The reaction is part of the aerobic respiration pathway. Although it is not part of either glycolysis or the citric acid cycle, it is often portrayed as part of one or the other for simplicity.

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Pyruvate decarboxylation reaction

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.

Regulation of pyruvate decarboxylation

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 respiration demand. Regulation by an allosteric mechanism.
• NADH - abundant in cells where oxidative phosphorylation cannot keep up with NADH production. Regulation by substrate inhibition.

• Promoters:

• Phosphoenolpyruvate - a late intermediate of active glycolysis.
• nucleotide monophosphates - abundant in cells with high ATP demand, and highly sensitive to changes in ATP.^{[citation needed]}
• calcium

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).

Localization 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 and is active, 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 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.

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.

Pyruvate oxidation

Pyruvate oxidation is the step which connects glycolysis to Krebs Cycle. It takes the two pyruvate molecules formed during glycolysis and transports them from the cytoplasm, through the two mitochondrial membranes into the mitochondrial matrix. Once inside, a multienzyme complex known as the pyruvate dehydrogenase complex catalyzes these changes:

1. A carboxyl group is removed as CO₂H, which diffuses out of the cell. As a result, the original pyruvate has now been converted into a two-carbon hydroxyethyl group.
2. The remaining two-carbon hydroxyethyl group has now been oxidized to an acetyl group.
3. A NAD+ accepts the electrons removed during the oxidation and is thereby reduced by two hydrogen atoms.
4. The acetyl group becomes attached to Coenzyme A, yielding acetyl-CoA.
5. The newly formed acetyl-CoA now moves on to Krebs Cycle.
6. NAD+ is reduced to NADH as the third enzyme of the pyruvate dehydrogenase complex restores the second enzyme's lipoamide to its oxidized state.

See also

• Glycolysis
• Citric acid cycle
• Cellular respiration
• Pyruvate
• Acetyl CoA
• Pyruvate dehydrogenase complex

References

• Alberts et al. Molecular Biology of the Cell. Garland Science, 2001. ISBN 0-8153-4072-9
• Notes on Pyruvate decarboxylation
• KEGG Pathway Database