TPH2

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TPH2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTPH2, ADHD7, NTPH, tryptophan hydroxylase 2
External IDsOMIM: 607478 MGI: 2651811 HomoloGene: 27831 GeneCards: TPH2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_173353

NM_173391

RefSeq (protein)

NP_775489

NP_775567

Location (UCSC)Chr 12: 71.94 – 72.19 MbChr 10: 114.91 – 115.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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,[5] 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.[6]

Function[edit]

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][7]

Disabling this enzyme with drugs (especially p-chlorophenylalanine aka PCPA and 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[8]). 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.[9] Drugs such as MDMA[10] and methamphetamine[11] 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".[12]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000139287 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000006764 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Walther DJ, Peter JU, Bashammakh S, Hörtnagl H, Voits M, Fink H, Bader M (January 2003). "Synthesis of serotonin by a second tryptophan hydroxylase isoform". Science. 299 (5603): 76. doi:10.1126/science.1078197. PMID 12511643. S2CID 7095712.
  6. ^ Zill P, Büttner A, Eisenmenger W, Möller HJ, Ackenheil M, Bondy B (2005). "Analysis of tryptophan hydroxylase I and II mRNA expression in the human brain: a post-mortem study". Journal of Psychiatric Research. 41 (1–2): 168–173. doi:10.1016/j.jpsychires.2005.05.004. PMID 16023677.
  7. ^ "Entrez Gene: TPH2 tryptophan hydroxylase 2".
  8. ^ Ferguson J, Henriksen S, Cohen H, Mitchell G, Barchas J, Dement W (April 1970). ""Hypersexuality" and behavioral changes in cats caused by administration of p-chlorophenylalanine". Science. 168 (3930): 499–501. Bibcode:1970Sci...168..499F. doi:10.1126/science.168.3930.499. PMID 5461688. S2CID 16691506.
  9. ^ Richard F, Sanne JL, Bourde O, Weissman D, Ehret M, Cash C, et al. (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. 536 (1–2): 41–45. doi:10.1016/0006-8993(90)90006-w. PMID 2150773. S2CID 12214077.
  10. ^ Bonkale WL, Austin MC (July 2008). "3,4-Methylenedioxymethamphetamine induces differential regulation of tryptophan hydroxylase 2 protein and mRNA levels in the rat dorsal raphe nucleus". Neuroscience. 155 (1): 270–276. doi:10.1016/j.neuroscience.2008.03.086. PMC 2505057. PMID 18515011.
  11. ^ Hotchkiss AJ, Gibb JW (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. 214 (2): 257–262. PMID 6104722.
  12. ^ Cremata VY, Koe BK (May 1968). "Clinical and biochemical effects of fenclonine: a serotonin depletor". Diseases of the Nervous System. 29 (5): Suppl:147–Suppl:152. PMID 5673619. Retrieved 2 July 2022.

Further reading[edit]