BCAT2

Branched-chain amino acid transaminase 2 (BCAT2), also termed mitochondrial BCAT (BCATm), catalyzes the reversible transamination of branched-chain amino acids (BCAAs; leucine, isoleucine, valine) to generate glutamate and corresponding α-keto acids (α-KIC, α-KIV, α-KMV) within mitochondria. This rate-limiting step channels BCAAs into the tricarboxylic acid (TCA) cycle via oxidative decarboxylation by the branched-chain α-ketoacid dehydrogenase (BCKDH) complex. BCAT2 critically links nitrogen metabolism with energy production, influencing mTORC1 signaling activation through leucine availability. Dysregulated BCAT2 expression is implicated in metabolic disorders (diabetes, obesity), hepatocellular carcinoma progression (via α-KG-mediated epigenetic modulation), and neurological conditions like Huntington’s disease. Recent studies highlight BCAT2 inhibition (e.g., gabapentinoid analogs or CRISPR-Cas9 knockout) as a therapeutic strategy to suppress tumor growth by depleting BCAA-derived oncometabolites. However, isoform-specific targeting remains challenging due to structural similarities with cytosolic BCAT1.