Branched-chain-amino-acid aminotransferase, mitochondrial (BCAT2) (BCAT2)

Branched-chain-amino-acid aminotransferase, mitochondrial (BCAT2) is a key enzyme responsible for the initial, reversible transamination of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine into their respective alpha-keto acids [1, 11]. Located in the mitochondria of most tissues, BCAT2 plays a vital role in nitrogen homeostasis, energy production, and the regulation of the mTOR signaling pathway [1, 11, 16]. Dysregulation of BCAT2 is implicated in various pathologies, including metabolic disorders like obesity and type 2 diabetes, where its expression is often suppressed in adipose tissue [17, 34]. Conversely, BCAT2 is frequently overexpressed in certain cancers, such as pancreatic ductal adenocarcinoma and colorectal cancer, where it supports rapid tumor growth by providing metabolic intermediates [2, 14, 16]. Therapeutic strategies targeting BCAT2 primarily involve the development of small-molecule inhibitors, such as BAY-069, LY3351337, and BCAT-IN-2, to disrupt BCAA catabolism in cancer cells or improve insulin sensitivity [15, 18, 24, 34]. Additionally, cofactors like pyridoxine are used to manage genetic deficiencies that lead to hypervalinemia [5, 12]. While several pharmaceutical companies are exploring BCAT2 as a target, most inhibitors remain in the preclinical stage of development [6, 15].

Other names

BCAT2 [1, 7]BCATm [3, 11]BCATM [5, 7]BCT2 [5, 7]ECA40 [5, 7]PP18 [5, 7]Placental protein 18 [5, 7]BCAM [7, 35]

Inhibition of the transamination of branched-chain amino acids (BCAAs) to their corresponding alpha-keto acids, thereby modulating metabolic pathways and signaling cascades such as mTOR [6, 9, 34].