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TPP is the key catalytic cofactor used by enzymes catalyzing non-oxidative and oxidative decarboxylation of α-keto acids. Pyruvate, for example, undergoes both types of decarboxylation, both involving TPP. In fermentative organisms, pyruvate is non-oxidatively decarboxylated by the TPP-dependent enzyme pyruvate decarboxylase.
Pyruvate oxidation is the step that connects glycolysis and the Krebs cycle. [4] In glycolysis, a single glucose molecule (6 carbons) is split into 2 pyruvates (3 carbons each). Because of this, the link reaction occurs twice for each glucose molecule to produce a total of 2 acetyl-CoA molecules, which can then enter the Krebs cycle.
It is an oxidative carboxylase that catalyses the oxidative decarboxylation of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP).
The oxidative conversion of pyruvate into acetyl-CoA is referred to as the pyruvate dehydrogenase reaction. It is catalyzed by the pyruvate dehydrogenase complex. Other conversions between pyruvate and acetyl-CoA are possible. For example, pyruvate formate lyase disproportionates pyruvate into acetyl-CoA and formic acid. β-Oxidation of fatty acids
This enzyme complex catalyzes the oxidative decarboxylation of branched, short-chain alpha-ketoacids. BCKDC is a member of the mitochondrial α-ketoacid dehydrogenase complex family, which also includes pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase , key enzymes that function in the Krebs cycle .
Pyruvate dehydrogenase deficiency (PDCD) can result from mutations in any of the enzymes or cofactors used to build the complex. Its primary clinical finding is lactic acidosis. [18] Such PDCD mutations, leading to subsequent deficiencies in NAD and FAD production, hinder oxidative phosphorylation processes that are key in aerobic respiration.
Pyruvate decarboxylation requires a few cofactors in addition to the enzymes that make up the complex. The first is thiamine pyrophosphate (TPP), which is used by pyruvate dehydrogenase to oxidize pyruvate and to form a hydroxyethyl-TPP intermediate. This intermediate is taken up by dihydrolipoyl transacetylase and reacted with a second ...
Pyruvate decarboxylase depends on cofactors thiamine pyrophosphate (TPP) and magnesium. This enzyme should not be mistaken for the unrelated enzyme pyruvate dehydrogenase, an oxidoreductase (EC 1.2.4.1), that catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA.