cysteine

Cysteine's sulfhydryl (-SH) group enables formation of disulfide bonds (cystine) between polypeptide chains, stabilizing protein structure (e.g., insulin, immunoglobulins, keratin). It is synthesized endogenously from methionine via the transsulfuration pathway (methionine → homocysteine → cystathionine → cysteine), making it conditionally essential—essential in neonates and in conditions of impaired hepatic function.

Clinical relevance: - Precursor for glutathione (antioxidant defense, detoxification of reactive oxygen species and xenobiotics via glutathione-S-transferase). N-acetylcysteine (NAC) is a cysteine derivative used clinically as a mucolytic (breaks disulfide bonds in mucus glycoproteins) and as the antidote for acetaminophen overdose (replenishes glutathione stores, preventing hepatotoxicity from NAPQI). - Precursor for taurine and coenzyme A synthesis. - Cystinuria: an autosomal recessive disorder (defect in PCT amino acid transporter for cystine, ornithine, lysine, arginine - COLA) leading to accumulation of cystine in urine and formation of hexagonal cystine kidney stones. Treated with hydration, urinary alkalinization, and chelating agents (e.g., penicillamine). - Homocystinuria: defect in cystathionine synthase (impairs conversion of homocysteine to cystathionine/cysteine) leads to elevated homocysteine and methionine, with low cysteine; associated with marfanoid habitus, lens dislocation (downward), thrombosis, and intellectual disability. Treated with B6, B12, folate supplementation, and cysteine supplementation in diet. - Cysteine residues are critical in enzyme active sites (e.g., caspases, cysteine proteases) and zinc finger motifs.