Bckdha, encoding the E1α subunit of the branched-chain α -ketoacid dehydrogenase (BCKDH) complex, is crucial for branched-chain amino acid (BCAA) catabolism. The BCKDH complex decarboxylates ketoacid derivatives of leucine, isoleucine, and valine, thus playing a significant role in amino acid metabolism pathways [3]. Genetic models, such as knockout mouse models, have been essential in studying its functions.

In melanoma, Bckdha expression is increased. Its up-regulation promotes melanoma cell proliferation, invasion, migration in vitro and tumour growth in vivo by regulating the expressions of lipogenic enzymes FASN and ACLY [1].

In hepatic gluconeogenesis, liver-specific knockout of Bckdha in mice shows normal glucose tolerance and insulin sensitivity, indicating that BCKDH kinase regulates hepatic gluconeogenesis independent of Bckdha-mediated BCAA catabolism [2].

In maple syrup urine disease (MSUD), which results from biallelic mutations in genes encoding components of the BCKDH complex including Bckdha, gene therapy using a dual-function recombinant adeno-associated virus to deliver Bckdha and Bckdhb can restore metabolic homeostasis in mouse models and a calf with classic MSUD [3].

In conclusion, Bckdha is essential for BCAA catabolism. Studies using knockout mouse models have revealed its role in diseases like melanoma, hepatic gluconeogenesis-related disorders, and MSUD. These findings contribute to understanding the underlying mechanisms of these diseases and developing potential therapeutic strategies.