Tryptophan 5-hydroxylase (TPH) (TPH)

Tryptophan 5-hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin, catalyzing the conversion of L-tryptophan to 5-hydroxytryptophan [UniProt: P17752]. It exists in two isoforms: TPH1, primarily expressed in the enterochromaffin cells of the gastrointestinal tract and the pineal gland, and TPH2, which is the predominant form in the central nervous system [PubMed: 12642636]. The enzyme's activity is strictly dependent on the presence of the cofactor tetrahydrobiopterin (BH4) [PubMed: 21484561]. L-methylfolate (5-MTHF) is a critical component in this system as it serves as a precursor for the synthesis and regeneration of BH4, thereby indirectly regulating TPH activity and serotonin production [StatPearls: NBK537259]. Clinically, TPH is a target for treating depression, where L-methylfolate is used as an adjunctive therapy to enhance monoamine synthesis, and for carcinoid syndrome, where TPH inhibitors like telotristat ethyl are used to reduce excessive peripheral serotonin production [PubMed: 28242203]. Understanding the interplay between TPH and its folate-dependent cofactors is essential for managing mood disorders and neuroendocrine tumors.

Other names

Tryptophan hydroxylaseTryptophan 5-monooxygenaseTPHTPH1TPH2

L-methylfolate increases the synthesis of tetrahydrobiopterin (BH4), which serves as the essential rate-limiting cofactor for tryptophan 5-hydroxylase, thereby facilitating the conversion of tryptophan to 5-hydroxytryptophan and increasing serotonin production [PubMed: 21484561, StatPearls: NBK537259].