Tryptophan 5-monooxygenase (TPH)

Tryptophan 5-monooxygenase, commonly known as tryptophan hydroxylase (TPH), is the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin (5-hydroxytryptamine) and the hormone melatonin (UniProt, NIH). It exists in two distinct isoforms: TPH1, which is primarily expressed in peripheral tissues like the gastrointestinal tract and pineal gland, and TPH2, which is the predominant form in the central nervous system (PubMed, Wikipedia). By catalyzing the hydroxylation of L-tryptophan to 5-hydroxytryptophan (5-HTP) using tetrahydrobiopterin and oxygen as cofactors, TPH plays a critical role in regulating mood, sleep, appetite, and gut motility (Frontiers, NIH). Dysregulation of TPH activity is linked to various conditions; TPH1 overactivity is associated with carcinoid syndrome and irritable bowel syndrome, while TPH2 dysfunction is implicated in neuropsychiatric disorders such as depression and anxiety (PubMed, ResearchGate). Pharmacological targeting of TPH includes inhibitors like telotristat ethyl, which reduces peripheral serotonin production to treat carcinoid syndrome-associated diarrhea (NIH, PubMed). Conversely, research into TPH2 activators or stabilizers aims to address serotonin deficiencies in the brain, though most current clinical strategies focus on inhibiting the peripheral isoform to avoid central nervous system side effects (Frontiers, NIH). Monitoring of TPH inhibition is typically achieved by measuring levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the urine (StatPearls, NIH).

Other names

Tryptophan hydroxylaseTPH1TPH2Tryptophan 5-hydroxylaseL-tryptophan, tetrahydrobiopterin:oxygen oxidoreductase (5-hydroxylating)

Inhibition of the rate-limiting step in serotonin biosynthesis by blocking the conversion of L-tryptophan to 5-hydroxytryptophan (NIH, PubMed).