Branched-chain alpha-keto acid dehydrogenase E1 subunit alpha (BCKDHA)

Branched-chain alpha-keto acid dehydrogenase E1 subunit alpha (BCKDHA) is the alpha subunit of the E1 component of the branched-chain alpha-keto acid dehydrogenase (BCKD) complex, a multi-enzyme complex located on the inner mitochondrial membrane. BCKDHA, in combination with the beta subunit (encoded by BCKDHB), catalyzes the first committed and irreversible step in the oxidative decarboxylation of branched-chain α-keto acids derived from the essential amino acids leucine, isoleucine, and valine. This reaction is a critical juncture in amino acid catabolism and energy metabolism. Mutations in BCKDHA lead to deficient complex activity and are the genetic cause of maple syrup urine disease, a rare but potentially lethal metabolic disorder. In affected individuals, impaired BCKD function causes accumulation of branched-chain amino acids and their toxic metabolites, resulting in severe neurological, developmental, and metabolic disturbances. The BCKDHA gene is therefore essential for amino acid homeostasis and normal cellular metabolism.

Other names

Branched chain keto acid dehydrogenase E1 subunit alpha2-oxoisovalerate dehydrogenase subunit alpha, mitochondrialBCKDE1ABCKDH E1-alphaMSUBranched-chain alpha-keto acid dehydrogenase E1 component alpha chainmaple syrup urine disease protein (MSUD1, MSUD1A)OVD1A

Inhibitors or loss-of-function (i.e., pathogenic mutations) block the oxidative decarboxylation of branched-chain α-keto acids, leading to accumulation of branched-chain amino acids and their toxic metabolites. Thiamine supplementation may enhance residual enzyme activity in some thiamine-responsive forms of maple syrup urine disease.