Valine, leucine, and isoleucine share the first two catabolic steps. (1) BCAT (branched-chain aminotransferase, tissue-distributed): reversible transamination → α-keto acids (KIC from leucine, KIV from valine, KMV from isoleucine). (2) BCKDH (branched-chain α-ketoacid dehydrogenase complex, mitochondrial; analogous to PDH + α-KGDH): oxidative decarboxylation. After that, each BCAA diverges to a different end product: valine + isoleucine are glucogenic (→ succinyl-CoA); leucine is purely ketogenic (→ acetoacetate + acetyl-CoA). BCKDH deficiency causes maple syrup urine disease (MSUD) — accumulated α-keto acids produce the characteristic odor + acute encephalopathy. Leucine specifically activates mTORC1 (see mtor_signaling); explains the BCAA-supplementation rationale for muscle hypertrophy.
Organ Systems
endocrine
musculoskeletal
digestive
Pathway Steps
leucine → alpha-ketoisocaproate — via BCAT — branched-chain aminotransferase (reversible). BCAT reversibly transaminates the branched-chain amino acids and is expressed mainly in muscle, not liver — so BCAAs largely escape first-pass hepatic metabolism and are catabolized peripherally, part of their appeal as a muscle supplement.
valine → alpha-ketoisovalerate — via BCAT. Valine’s carbon skeleton is glucogenic (→ propionyl-CoA → succinyl-CoA), unlike purely ketogenic leucine — so the three BCAAs share the first two steps but diverge in metabolic fate afterward.
isoleucine → alpha-keto-3-methylvalerate — via BCAT. Isoleucine is both glucogenic and ketogenic, yielding succinyl-CoA and acetyl-CoA. All three branched-chain α-keto acids converge on the single BCKDH complex for their committed oxidative decarboxylation.
alpha-ketoisocaproate → acetyl-coa — via BCKDH complex — MSUD enzyme; multi-step continues. The branched-chain α-ketoacid dehydrogenase complex is the rate-limiting, irreversible step — analogous to PDH and sharing thiamine/lipoate/FAD/NAD/CoA. Its deficiency causes maple syrup urine disease; it is switched off by kinase (BDK) phosphorylation and on by the phosphatase PPM1K.
Known Modulators
leucine (activator) — mTORC1 (Sestrin/GATOR — see mtor_signaling)
hmb (substrate) — leucine metabolite (β-hydroxy-β-methylbutyrate). leucine catabolite; anti-catabolic claim; muscle preservation in aging + cancer cachexia