Tryptophan is an essential amino acid that cannot be synthesized in the body and must be obtained via one's diet. Tryptophan hydroxylase (Tph) is the enzyme responsible for converting tryptophan into serotonin (5-HT).
Since the discovery of the two types of Tph (Tph1 and Tph2), it has become widely accepted that the central and peripheral 5-HT systems are functionally separate. Because serotonin cannot cross the blood-brain barrier, Tph2 biosynthesizes 5-HT centrally, and Tph1 does so peripherally.
Professor Katsunori Nonogaki and colleagues at Tohoku University have discovered that Tph1 regulates tryptophan and its metabolites in the plasma and brain.
Using genetically modified mice lacking Tph1, the researchers found that plasma and brain levels of tryptophan and its metabolites in young Tph1 mutants were significantly lower than those in age-matched wild-type mice. Interestingly, the decline in plasma levels of tryptophan and its metabolites outside the 5-HT pathway was diminished in older Tph1 mutants.
Moreover, Nonogaki and his colleagues found that Tph1 regulates blood glucose homeostasis independently of feeding and insulin. Although Tph1 mutants displayed age-related alterations in food intake and plasma FGF21 and insulin levels, blood glucose levels were lower in both young and older Tph1 mutants than those in age-matched wild-type mice.
Details were published in the International Journal of Molecular Sciences on April 23, 2025.
- Publication Details:
Title: Tryptophan hydroxylase 1 regulates tryptophan and its metabolites
Authors: Katsunori Nonogaki and Takao Kaji
Journal: International journal of Molecular Sciences
DOI: 10.3390/ijms26093978
