Branched-chain amino acid transaminase (BCAT) (BCAT)

Branched-chain amino acid transaminase (BCAT) is a family of pyridoxal phosphate-dependent enzymes, consisting of cytosolic (BCAT1) and mitochondrial (BCAT2) isoforms, that catalyze the first step in the catabolism of the essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine (Frontiers, 2024). This enzyme facilitates a reversible transamination reaction, transferring an amino group to alpha-ketoglutarate to form glutamate and corresponding branched-chain alpha-ketoacids (BCKAs), thereby playing a critical role in cellular nitrogen and energy homeostasis (PMC, 2022). In many aggressive human cancers, such as glioblastoma, leukemia, and breast cancer, BCAT1 is frequently upregulated and serves as a key driver of metabolic reprogramming, activating oncogenic pathways like mTORC1 and Wnt/beta-catenin to promote rapid cell proliferation and therapeutic resistance (Frontiers, 2024; PMC, 2022). Conversely, dysregulation or deficiency of BCAT activity is implicated in neurodegenerative conditions like Alzheimer’s disease and metabolic disorders such as type 2 diabetes and obesity (PubMed, 2025). Pharmacological inhibition of BCAT, particularly the BCAT1 isoform, is an emerging therapeutic strategy aimed at disrupting the metabolic dependencies of cancer cells (Current Medicinal Chemistry, 2025). While specific small-molecule inhibitors like BAY-069 are in preclinical development, the anticonvulsant gabapentin is a recognized research tool that interacts with BCAT1. Key therapeutic challenges include managing the risk of metabolic toxicities resembling maple syrup urine disease and ensuring selectivity between the metabolic roles of BCAT1 and the ubiquitous mitochondrial BCAT2 (PMC, 2022).

Other names

Branched-chain amino acid aminotransferaseBCAA transaminaseBCAT1BCAT2Cytosolic branched-chain amino acid aminotransferaseMitochondrial branched-chain amino acid aminotransferaseBCATcBCATmECA39

Inhibition of the enzymatic transamination of branched-chain amino acids (leucine, isoleucine, and valine) to their corresponding alpha-ketoacids, thereby suppressing BCAA-mediated activation of the mTORC1 pathway and depleting the glutamate pool used for tumor metabolism and antioxidant defense.