Branched-chain amino acid aminotransferase (BCAT)

Branched-chain amino acid aminotransferase (BCAT) is a PLP-dependent enzyme that catalyzes the reversible transamination of the branched-chain amino acids leucine, isoleucine, and valine to their respective keto acids, regulating both their breakdown and synthesis. Humans express two BCAT isoforms: mitochondrial (BCAT2), found in many tissues, and cytosolic (BCAT1), mainly in the CNS. BCATs play crucial roles in amino acid and nitrogen metabolism, neurotransmitter (glutamate) production, and are increasingly recognized as metabolic regulators in cancer cells, where altered expression can drive tumor growth and therapy resistance via key metabolic and signaling pathways. Their tissue-specific and disease-type-specific functions make them promising but challenging targets for therapeutic intervention in oncology, inherited metabolic diseases, and CNS disorders. Note: There are no widely used, approved drugs that directly target BCATs clinically, but gabapentin acts on the cytosolic form in the CNS, and BCAT is being actively investigated for novel drug discovery in oncology and metabolism. Detection of BCAT1/2 expression and BCAA levels serve as emerging biomarkers in cancer and metabolic disease research. Safety/toxicity concerns relate to the enzyme's central metabolic role.

Other names

Branched-chain amino acid transaminaseBCAT (common abbreviation, also refers collectively to the family)BCAT1 (cytosolic isoform, mainly in CNS)BCAT2 (mitochondrial isoform, widespread in tissues)BcaT (used in microbial and plant literature)Aminotransferase, class IV (structural family)

Transaminase inhibition: Drugs like gabapentin inhibit BCAT activity, reducing glutamate synthesis. Metabolic reprogramming modulation: Potential inhibition of BCATs to disrupt amino acid supply in cancer cells, affecting mTOR and PI3K/Akt signaling. BCAA manipulation: Therapeutics altering BCAA metabolism for metabolic or neurologic diseases.