Branched-chain amino acids (BCAA)

Branched-chain amino acids (BCAAs) are a group of three essential amino acids—leucine, isoleucine, and valine—distinguished by their branched aliphatic side chains. They play a fundamental role in human physiology as both building blocks for protein synthesis and as metabolic signals that regulate the mTORC1 signaling pathway, which is critical for cell growth and muscle recovery [1, 3, 17]. Unlike most amino acids that are processed in the liver, BCAAs are primarily catabolized in extrahepatic tissues like skeletal muscle and the brain, making them vital energy sources during exercise and stress [1, 4]. In clinical practice, BCAAs are utilized as therapeutic supplements for conditions such as hepatic encephalopathy in liver cirrhosis, sarcopenia, and certain movement disorders [5, 18]. However, dysregulated BCAA metabolism is a hallmark of several major diseases; for instance, elevated circulating levels are strong biomarkers for insulin resistance and type 2 diabetes [3, 15]. Furthermore, many cancers upregulate BCAA transporters and enzymes (like BCAT1) to fuel rapid proliferation, leading to emerging research into targeting BCAA metabolic pathways as a novel strategy for oncological therapy [7, 8, 12].

Other names

LeucineIsoleucineValineEssential branched-chain amino acidsBCAAs

Branched-chain amino acids (BCAAs) serve as essential substrates for muscle protein synthesis and act as potent signaling molecules that activate the mTORC1 (mechanistic target of rapamycin complex 1) pathway, particularly through the leucine-sensor Sestrin2 [1, 11, 17]. They are catabolized via a two-step process involving transamination by Branched-chain aminotransferase (BCAT) and oxidative decarboxylation by the Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, providing carbon skeletons for the TCA cycle and nitrogen for glutamate synthesis [4, 6, 13].