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pyruvate decarboxylation to acetyl CoA

2-oxo acid dehydrogenase complexes convert 2-oxo acids to the corresponding acyl-CoA derivatives and produce NADH and : CARBON-DIOXIDE in an irreversible reaction. Five members of this family are known at present, including the : PYRUVATEDEH-CPLX (PDHC- this pathway), the : 2OXOGLUTARATEDEH-CPLX , (OGDHC), the : CPLX-6940 (BCDHC), the : GLYCLEAV-PWY (GDHC), and the acetoin dehydrogenase complex (ADHC). They all function at strategic points in (usually aerobic) catabolic pathways and are subject to stringent control . With the exception of GDHC, the 2-oxo acid dehydrogenase complexes share a common structure. They consist of three main components, namely a 2-oxo acid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). In mitochondria, the E1 component is a heterodimer composed of two subunits. Many copies of each subunit assemble to form the full complex. components, respectively. The core is made of either 24 or 60 E2 units, which contain the lipoyl active site in the form of lipoyllysine, as well as binding sites for the other two subunits. E1, which contains a : THIAMINE-PYROPHOSPHATE cofactor, catalyzes the binding of the 2-oxo acid to the lipoyl group of E2, which then transfers an acyl group (the nature of the acyl group depends on the particular enzyme) to : CO-A, forming an acyl-CoA, while reducing the lipoyl group to dihydrolipoyl. E3 then transfers the protons to NAD, forming NADH and restoring the dihydrolipoyllysine group back to lipoyllysine. Cryoelectron microscopy of PDHC from ox kidney has revealed that the E2 inner core is surrounded by an outer shell of E1 and E3 components, with the lipoyl domains confined to the annular space between them where they must make successive journeys between the three types of active sites (E1-E3), which are physically far apart. In the pathway illustrated here, : PYRUVATE is converted to : ACETYL-COA and : CARBON-DIOXIDE, a key reaction of central metabolism, which links the substrate-level phosphorylation pathway : GLYCOLYSIS (which ends with the generation of : PYRUVATE) to the : TCA, which accepts the input of : ACETYL-COA. The reactions catalyzed by the : PYRUVATEDEH-CPLX can be summarized by the reaction :PYRUVDEH-RXN. The net consequence of the cycle, in addition to reducing : NAD, is the conversion of : PYRUVATE into : ACETYL-COA and : CARBON-DIOXIDE, a key reaction of central metabolism because it links : GLYCOLYSIS, which generates : PYRUVATE, to the : TCA, into which the : ACETYL-COA flows. The cycle is an essential source of : ACETYL-COA to feed the : TCA and thereby to satisfy the cellular requirements for the precursor metabolites it forms.

Type: pathway
Taxonomic scope
organism-specific biosystem
Homo sapiens

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