Branched-chain-amino-acid aminotransferase, cytosolic (BCAT1) (BCAT1)

Branched-chain-amino-acid aminotransferase, cytosolic (BCAT1) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the first step in the catabolism of branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine [1, 9]. It facilitates the reversible transamination of BCAAs and alpha-ketoglutarate to produce branched-chain alpha-keto acids and glutamate [9, 10]. While the mitochondrial isoform BCAT2 is ubiquitously expressed, BCAT1 expression is normally restricted to the brain and certain other tissues but is frequently upregulated in various cancers, such as glioblastoma, acute myeloid leukemia, and hepatocellular carcinoma [1, 4, 7]. In these malignancies, BCAT1 promotes tumor growth and progression by providing nitrogen for biosynthetic processes, activating the mTORC1 and Wnt/beta-catenin signaling pathways, and modulating the epigenetic landscape through its impact on alpha-ketoglutarate levels [1, 2, 3]. Due to its critical role in cancer metabolism and its association with poor prognosis, BCAT1 is considered a promising therapeutic target and a potential biomarker for disease monitoring [2, 6, 13]. Therapeutic strategies currently under investigation include small-molecule inhibitors like BAY-069 and the use of BCAT1 DNA methylation as a non-invasive diagnostic marker [6, 15].

Other names

BCATCBCT1ECA39MECA39PNAS121PP18Branched-chain aminotransferase 1Branched-chain-amino-acid aminotransferase, cytosolic

Inhibition of BCAT1 enzyme activity to disrupt branched-chain amino acid catabolism, reduce glutamate and alpha-ketoglutarate production, and suppress downstream oncogenic signaling pathways such as mTORC1 and Wnt/beta-catenin [1, 2, 6].