description
The 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. Other members of this family include the : PYRUVATEDEH-CPLX (PDHC), the : 2OXOGLUTARATEDEH-CPLX (OGDHC), the : CPLX-6940 (BCDHC - this pathway) and the : GLYCLEAV-PWY (GDHC). They all function at strategic points in (usually aerobic) catabolic pathways and are subject to stringent control . 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 a dihydrolipoamide dehydrogenase (E3). In mitochondria the E1 component is a heterodimer composed of two subunits. In all cases described so far many copies of each subunit assemble to form the full complex. For example, the : TAX-83333 : PYRUVATEDEH-CPLX comprises of 24, 24, and 12 units of the E1, E2, and E3 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 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 : 2-KETO-ISOVALERATE, a transamination product of : VAL, is used as an example for the 2-oxo acid substrate of the branched-chain dehydrogenase complex (BCDHC). This reaction is summarized by the EC entry 1.2.1.25 (: 1.2.1.25-RXN). BCDHC can also recognize : 2K-4CH3-PENTANOATE and : 2-KETO-3-METHYL-VALERATE (which are the transamination products of : LEU and : ILE, respectively), and plays a key role in the degradation of : VAL, : LEU, and : ILE

external resources
NCBI:142335
BIOCYC:HUMAN_PWY-5046
PUBMED:9655933
PUBMED:12795594

genes
BCKDHA , BCKDHB , DBT , DLD ,