CoA (coenzyme A) is the central acyl-carrier in metabolism — present in acetyl-CoA, succinyl-CoA, fatty acyl-CoA, HMG-CoA, every acyl-CoA species. Biosynthesized from pantothenate (vitamin B5) via five enzymatic steps: pantothenate → 4'-phosphopantothenate (PANK1-4, RATE-LIMITING) → 4'-phospho-N-pantothenoylcysteine → 4'-phosphopantetheine → dephospho-CoA → CoA. PANK2 deficiency causes PKAN (pantothenate kinase-associated neurodegeneration, formerly Hallervorden-Spatz) — autosomal recessive with iron accumulation in basal ganglia ("eye-of-the-tiger" MRI sign); experimental treatment with deferiprone + fosmetpantotenate. Holo-acyl carrier protein (ACP, fatty acid synthase component) also uses the phosphopantetheine arm.
Organ Systems
endocrine
musculoskeletal
Pathway Steps
pantothenate → 4-prime-phosphopantothenate — via pantothenate kinase (PANK1-4) — RATE-LIMITING; PKAN deficiency. Pantothenate kinase (vitamin B5 → its phosphate) is the rate-limiting, feedback-regulated committed step of CoA synthesis. PANK2 mutations cause PKAN (pantothenate-kinase-associated neurodegeneration), a brain iron-accumulation disorder.
4-prime-phosphopantothenate → coa — via multi-step (PPCS + PPCDC + COASY). Subsequent steps add cysteine and an ADP moiety to build coenzyme A — the universal acyl carrier (acetyl-, malonyl-, succinyl-, fatty-acyl-CoA) central to nearly all intermediary metabolism, so CoA availability broadly gates acyl-group chemistry.