Background:
Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin by converting tryptophan to 5-hydroxy-L-tryptophan. Two isoforms of TPH exist: TPH-1 is mainly expressed in the periphery, whereas the expression of TPH-2 is restricted to neuronal cells and the central nervous system. Most of the serotonin found throughout the body is synthesized by TPH-1 in enterochromaffin cells of the gastrointestinal tract. Targeted disruption of the tph1 gene results in low levels of circulating and tissue serotonin.