TPH2

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title: "TPH2" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["biology-of-bipolar-disorder"] description: "Protein-coding gene in the species Homo sapiens" topic_path: "science/biology" source: "https://en.wikipedia.org/wiki/TPH2" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Tryptophan hydroxylase 2 (TPH2) is an isozyme of tryptophan hydroxylase found in vertebrates. In humans, TPH2 is primarily expressed in the serotonergic neurons of the brain, with the highest expression in the raphe nucleus of the midbrain. Until the discovery of TPH2 in 2003, serotonin levels in the central nervous system were believed to be regulated by serotonin synthesis in peripheral tissues, in which tryptophan hydroxylase is the dominant form.

Function

Tryptophan hydroxylase (TPH; EC 1.14.16.4) is the rate-limiting enzyme in the synthesis of serotonin (5-hydroxytryptamine, or 5HT). 5HT is causally involved in numerous central nervous activities, and it has several functions in peripheral tissues, including the maintenance of vascular tone and gut motility.[supplied by OMIM]

Disabling this enzyme with drugs (especially p-chlorophenylalanine aka PCPA or Fenclonine) has allowed researchers to investigate the effects of very low serotonin levels on humans and others animals, and by extension, gain insights into the functions of serotonin systems more broadly (such as hypersexuality in rodents as well as increased aggression and hypersexuality cats following PCPA administration). In rat brain, administration of a single PCPA injection resulted in the lowest level of serotonin production occurring on day 2 and returning to control values on day 7. Drugs such as MDMA and methamphetamine have been shown to lower levels of this enzyme which may result in periods of low serotonin levels following drug use. In a study investigating the effects of Fenclonine on humans, the greatly lowered serotonin levels were associated with "fatigue, dizziness, nausea, uneasiness [anxiety], fullness in the head [a feeling of pressure in the head] paresthesias [a pricking, pins-and-needles, burning, and/or aching sensation--typically the limbs], headache, and constipation".

References

References

1. (January 2003). "Synthesis of serotonin by a second tryptophan hydroxylase isoform". Science.
2. (2005). "Analysis of tryptophan hydroxylase I and II mRNA expression in the human brain: a post-mortem study". Journal of Psychiatric Research.
3. "Entrez Gene: TPH2 tryptophan hydroxylase 2".
4. (April 1970). ""Hypersexuality" and behavioral changes in cats caused by administration of p-chlorophenylalanine". Science.
5. (December 1990). "Variation of tryptophan-5-hydroxylase concentration in the rat raphe dorsalis nucleus after p-chlorophenylalanine administration. I. A model to study the turnover of the enzymatic protein". Brain Research.
6. (July 2008). "3,4-Methylenedioxymethamphetamine induces differential regulation of tryptophan hydroxylase 2 protein and mRNA levels in the rat dorsal raphe nucleus". Neuroscience.
7. (August 1980). "Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain". The Journal of Pharmacology and Experimental Therapeutics.
8. (May 1968). "Clinical and biochemical effects of fenclonine: a serotonin depletor". Diseases of the Nervous System.

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