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pyruvate decarboxylation to acetyl CoA

Background 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 : CPLX66-272, the : CPLX66-42, (OGDHC), the : CPLX-7050 (BCDHC) and : CPLX66-539 (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). The E1 component is a heterodimer composed of two subunits. Many copies of each subunit assemble to form the full complex . 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 . About this Pathway The : CPLX66-272 (PDH) is a large dodecahedral multi-enzyme complex located in the mitochondrial matrix of eukaryotes. It is made up of about 96 subunits organized into three functional enzymes in humans: 20-30 copies of : CPLX66-269, 60 copies of : HS07688-MONOMER, and 6 copies of : CPLX-7868 (E3). The : ENSG00000110435-MONOMER is involved in the interaction between the E2 and E3 subunits . Within the mammalian PDH complex, the E2 subunit forms the structural core and accepts acetyl groups from E1 and transfers them 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. The pyruvate dehydrogenase complex plays a critical role in determining whether glucose-linked substrates are converted to : ACETYL-COA. When carbohydrate stores are reduced, mammalian pyrvuate dehydrogenase activity is down-regulated and limits the oxidative utilization of glucose in most non-neural tissues. : PYRUVATE "Pyruvate" enters the mitochondia via the recently identified : CPLX66-471 . The irreversible decarboxylation of : PYRUVATE to : ACETYL-COA and : CARBON-DIOXIDE with the concommitant reduction of : NAD is a key reaction of central metabolism because it links : PWY66-400 to the : PWY66-398. The cycle is an essential source of : ACETYL-COA to feed the : PWY66-398. This process is fundamental to the aerobic oxidation of glucose and is of particular importance in the brain where it is the obligatory pathway for energy generation under normal conditions . Four pyruvate dehydrogenase kinase (PDK) isozymes (: CPLX66-320 "PDK1", : CPLX66-321 "PDK2", : CPLX66-319 "PDK3", : CPLX66-322 "PDK4"), and two isoforms of pyruvate dehydrogenase phosphatase (: CPLX66-323 "PDP1", : CPLX66-325 "PDP2") control the activity state of PDC by determining the proportion of the pyruvate dehydrogenase (E1) component that is in the active, nonphosphorylated state .

from BIOCYC source record: HUMAN_PYRUVDEHYD-PWY
Type: pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
BSID:
142412

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