Production and Peripheral Roles of 5-HTP, a Precursor of Serotonin

Serotonin (5-hydroxytryptamine [5-HT]) has been implicated in a variety of physiological and pathological functions. Multiple steps of enzyme reactions enable biosynthesis of 5-HT. The first and rate-limiting step of the reaction is the synthesis of 5-hydroxy-L-tryptophan (5-HTP) from L-tryptophan. This step is dictated by an enzyme, tryptophan hydroxylase (TPH). TPH requires 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) as a co-substrate of TPH. 5-HTP has been simply regarded as a precursor of 5-HT and it is believed that the biological significance of 5-HTP is essentially ascribed to the production of 5-HT. However, recent works shed light on the specific functions of 5-HTP in the periphery. In this review article, we focus on the specific roles of exogenous 5-HTP as well as the endogenous 5-HTP in the gut epithelial cells. Since systemic treatment with 5-HTP is applied to patients with lower 5-HT levels, the studies on the specific role of 5-HTP might create an opportunity to explore the effects of exogenously-applied 5-HTP in the gut in man.