BCKDHA
BCKDHA (branched chain keto acid dehydrogenase E1 subunit alpha, also known as MSU and OVD1A) is the alpha subunit of the E1 decarboxylase component of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. It acts in the catabolism of valine, leucine and isoleucine. Browse Assay Genie's current range of BCKDHA research reagents below, or read on for the biology behind the target.
BCKDHA, together with BCKDHB, forms the heterotetrameric (alpha2-beta2) E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The complex catalyses the multi-step oxidative decarboxylation of alpha-ketoacids derived from the branched-chain amino acids valine, leucine and isoleucine, producing CO2 and acyl-CoA, which is subsequently used to produce energy. The E1 subunit carries out the first step, decarboxylating the alpha-ketoacid to form an enzyme-product intermediate. A reductive acylation mediated by the lipoylamide cofactor of E2 then extracts the acyl group from the E1 active site for the next step of the reaction.
The BCKD complex is an inner mitochondrial enzyme complex with three catalytic components: the E1 branched-chain alpha-keto acid decarboxylase, a dihydrolipoyl transacylase (E2) and a dihydrolipoamide dehydrogenase (E3). The BCKDHA gene encodes the alpha subunit of E1, and the protein is found in the mitochondrial matrix. It belongs to the BCKDHA family and is classed by HGNC among the branched chain alpha-keto acid dehydrogenase complex subunits and the oxidoreductases. Multiple transcript variants encoding different isoforms have been reported. Mouse and rat orthologs are both named Bckdha.
Mutations in the BCKDHA gene result in maple syrup urine disease, type IA, which is reflected in the earlier gene name "branched chain keto acid dehydrogenase E1, alpha polypeptide (maple syrup urine disease)" and in the alias MSU. The enzyme has also been called 2-oxoisovalerate dehydrogenase (lipoamide), giving the alias OVD1A and the UniProt name 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial.
BCKDHA is part of the complex that catalyses a major step in the catabolism of leucine, isoleucine and valine.
Mutations in BCKDHA cause maple syrup urine disease, type IA, making the gene a focus for studies of this metabolic disorder.
As the E1 decarboxylase alpha subunit, BCKDHA is used to study multienzyme complex assembly and the E1, E2 and E3 reaction sequence.
The acyl-CoA produced by the BCKD complex is subsequently used to generate energy, linking BCKDHA to mitochondrial fuel utilisation.
BCKDHA is the alpha subunit of the E1 component of the mitochondrial BCKD complex. With BCKDHB it forms an alpha2-beta2 tetramer that decarboxylates alpha-ketoacids derived from valine, leucine and isoleucine, the first step in producing CO2 and acyl-CoA.
HGNC names the gene branched chain keto acid dehydrogenase E1 subunit alpha. Aliases include MSU and OVD1A, and UniProt lists the protein as 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (EC 1.2.4.4). Multiple transcript variants encoding different isoforms have been described.
Mouse and rat both have a Bckdha ortholog. In humans, mutations in BCKDHA result in maple syrup urine disease, type IA. Check the datasheet of any product for its validated reactivity.
Other subunits and regulators of the branched-chain alpha-ketoacid dehydrogenase complex and related mitochondrial metabolism targets.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P12694; product specifications from Assay Genie datasheets.