Category: biosynthesis
Tryptophan is the obligatory precursor for both serotonin (5-HT) and melatonin. Tryptophan hydroxylase (TPH) is rate-limiting and exists as TPH1 (peripheral, enterochromaffin cells; ~90% of body 5-HT pool is gut) and TPH2 (CNS-restricted; brain 5-HT pool). AADC then converts 5-HTP to serotonin. In pineal gland, serotonin is N-acetylated (AANAT, the circadian-gated enzyme) and O-methylated (HIOMT/ASMT) to melatonin — concentrations rise sharply at dusk under SCN drive.