BCKDH synthesizes BCAA-CoA from KIC, KMVA, KIV

The mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex catalyzes the reactions of alpha-ketoisocaproate, alpha-keto beta-methylvalerate, or alpha-ketoisovalerate with CoA and NAD+ to form isovaleryl-CoA, alpha-methylbutyryl-CoA, or isobutyryl-CoA, respectively, and CO2 and NADH. While bovine and microbial BCKD complexes have been characterized most extensively, structural studies of individual components and subcomplexes of human BCKD have confirmed their structures and roles in the overall oxidative decarboxylation process and have related these features to the disruptive effects of mutations on branched-chain amino acid metabolism in vivo: E1a and E1b components, E2, and E3 (DLD). In addition, structural studies have confirmed the lipoylation of lysine residue 105 in E2 protein and the loss of an aminoterminal mitochondrial transport sequence from mature E3 protein. Loss of mitochondrial transport sequences from proteins E1a, E1b, and E2 has been demonstrated by sequence analysis. Defects in E1a, E1b, and E2 may cause so-called maple syrup urine disease, with accumulation of the abovementioned amino acids and their corresponding keto acids, leading to encephalopathy and progressive neurodegeneration (MSUD, MIM:248600; reviewed in Xu et al., 2020). Defects in the E3 (DLD) subunit, shared with other ketoacid dehydrogenase complexes, typically present as neonatal lactic acidosis due to lack of pyruvate dehydrogenase activity although symptoms of BCKDH deficiency may also be present.

Summary from Reactome (R-HSA-9859138), read 2026-09-23.