Wednesday, August 10, 2011

Oxidation of pyruvate

Under aerobic conditions, most eukaryotic cells and various bacteria oxidize the pyruvate, produced in glycolysis, to CO2 and H2O, instead of reducing it to lactate or ethanol.
Production of acetyl-CoA from pyruvateThe molecules of acetyl-CoA are the form in which the Krebs cycle accepts most of its fuel. Pyruvate is oxidized to acetyl-CoA and CO2 by an enzyme complex (3 enzymes) called pyruvate dehydrogenase complex. This complex is located in the mitochondria (eukaryotes) or cytosol (prokaryotes).
The oxidation of pyruvate to acetyl-CoA is an example of an irreversible oxidative decarboxylation. The irreversibility of the reaction was demonstrated by proving that when radiolabelled CO2 was used, pyruvate  with radioactive carbon was not be obtained.
In addition to acetyl-CoA and CO2, this reaction produces a molecule of NADH from NAD+.The pyruvate dehydrogenase complex requires the action of five cofactors: thiamine pyrophosphate (TPP), flavin adenine dinucleotide (FAD), coenzyme A (CoA), nicotinamide adenine dinucleotide (NAD +) and lipoate. 4 necessary vitamins in human nutrition are vital components of this system: thiamine (for TPP), riboflavin (for FAD), niacin (to NAD) and pantothenate (for CoA).

The enzymes that compose the pyruvate dehydrogenase complex are pyruvate dehydrogenase, and dihydrolipoyl transacetilase dihydrolipoyl dehydrogenase. Each of these enzymes is present in multiple copies.
Animals deprived of thiamine are usually unable to oxidize pyruvate. This has implications especially in the brain that usually gets all its energy from glucose oxidation, a process that necessarily involves the oxidation of pyruvate. Beriberi is a vitamin deficiency caused by thiamine deficiency. It is characterized by a loss of neuronal function. This disease is more common in populations that eat predominantly white rice (polished), because it is in rice husks that most of its thiamine is found.
Mutations in genes that encode subunits of this enzyme complex, as well as a diet deficient in thiamine can have serious consequences.

Main bibliographic sources:
- Quintas A, Freire AP, Halpern MJ, Bioquímica - Organização Molecular da Vida, Lidel
- Nelson DL, Cox MM, Lehninger - Principles of Biochemistry, WH Freeman Publishers