Pyruvate Dehydrogenase


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Pyruvate Dehydrogenase

 

a polyenzymatic complex that catalyzes the oxidative decarboxylation of pyruvic acid:

This reaction is the main pathway for the conversion of alpha keto acids in the tissues of animals, plants, and aerobic microorganisms; it links the two most important metabolic processes— glycolysis and the reactions of the tricarboxylic acid cycle. The vitamin derivatives thiamine pyrophosphate (TPP), coenzyme A (CoA), flavine-adenine dinucleotide (FAD), nicotinamide-adenine dinucleotide (NAD), lipoic acid, and Mg2+ ions all take part in the catalytic activity of pyruvate dehydrogenase. Magnesium ions are also necessary cofactors of the enzymes pyruvate decarboxylase, lipoyl transacetylase, and lipoyl dehydrogenase. The enzymes are present in specific quantitative relationships and fix the structure of the enzyme complex, which does not dissociate under normal conditions.

Pyruvate dehydrogenase that is extracted from animal organs and bacteria is a large protein aggregate with a molecular weight that ranges from 4,800,000 to 10,000,000 depending on its source. The complex ranges in size from 300 to 400 angstroms and is regulated by a variety of factors. In living organisms, pyruvate dehydrogenase is inhibited by phosphorylation of the decarboxylase component and reactivated upon splitting of the phosphate radical; the activity is also dependent on the energetic and hormonal state of the organism.

REFERENCE

Glemzha, A. A. “Piruvatdegidrogenaza: mekhanizm deistviia i struktura.” In the collection Uspekhi biologicheskoi khimii. Moscow, 1969.

L. S. KHAILOVA

References in periodicals archive ?
Subsequently, pyruvate enters the citric acid cycle and is converted to acetyl-CoA, H, C[O.sub.2], and NADH by pyruvate dehydrogenase complex (PDHC)-catalyzed oxidative decarboxylation.
Erk regulation of pyruvate dehydrogenase flux through pdk4 modulates cell proliferation.
Early responses in MDM were associated with increased levels of phosphofructokinase (PFK) activator PFKFB3, which assists in the production of pyruvate from glucose and pyruvate dehydrogenase complex component X (PDHX), which may facilitate acetyl-CoA production from pyruvate.
Dang, "HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia," Cell Metabolism, vol.
Growing evidence suggests that overexpressing PDK2, in line with higher pyruvate dehydrogenase alpha subunit (PDHa) phosphorylation status, is related to increased lactate production displayed by rat brain astrocytes (31) and breast cancer MCF7 cells (20).
Yan et al., "Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms," Progress in Nucleic Acid Research and Molecular Biology, vol.
Examples include hepatic failure, defects in gluconeogenesis, or a decreased breakdown of lactate due to a deficiency in pyruvate dehydrogenase (i.e., thiamine deficiency) [8].
PPAR[gamma] can increase glucose uptake inducing GLUT4 expression, contributes to glycolysis initiation by inducing glucokinase expression, and inhibits the tricarboxylic acid cycle by enhancing pyruvate dehydrogenase kinase (PDK) 4 expression.
Taherzadeh, "Inhibition effects of furfural on alcohol dehydrogenase, aldehyde dehydrogenase and pyruvate dehydrogenase," Biochemical Journal, vol.
Anti-mitochondrial antibodies (AMA) directed against the E2 subunit of pyruvate dehydrogenase (PDH-E2) which is a member of the inner mitochondrial membrane-expressed oxoacid dehydrogenase complex, and ketoglutarate dehydrogenase are present in 95% of the patients3.
Lactate can only be metabolized in the presence of the enzyme pyruvate dehydrogenase (PDH)[10] Figure 3 back to pyruvate, which then enters the gluconeogenic pathway or enters the mitochondria to be metabolized to acetyl CoA by the enzyme pyruvate dehydrogenase (PDH)." Acetyl CoA then enters the Kreb's cycle to produce C[O.sub.2], water and 38 molecules of ATP.
PDK1, a protein kinase that phosphorylates and thus inactivates pyruvate dehydrogenase alpha subunit, was more than 2-fold over expressed in frataxin knockdown cells.