Tryptophan hydroxylase 2 (TPH2) is an isozyme of tryptophan hydroxylase found in vertebrates. In humans, TPH2 is primarily expressed in the serotonergicneurons 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
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]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Walther DJ, Peter JU, Bashammakh S, Hörtnagl H, Voits M, Fink H, Bader M (Jan 2003). "Synthesis of serotonin by a second tryptophan hydroxylase isoform". Science. 299 (5603): 76. doi:10.1126/science.1078197. PMID12511643.
^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): 168–73. doi:10.1016/j.jpsychires.2005.05.004. PMID16023677.
Walther DJ, Peter JU, Bashammakh S, Hörtnagl H, Voits M, Fink H, Bader M (Jan 2003). "Synthesis of serotonin by a second tryptophan hydroxylase isoform". Science. 299 (5603): 76. doi:10.1126/science.1078197. PMID12511643.
Breidenthal SE, White DJ, Glatt CE (Jun 2004). "Identification of genetic variants in the neuronal form of tryptophan hydroxylase (TPH2)". Psychiatric Genetics. 14 (2): 69–72. doi:10.1097/01.ypg.0000107929.32051.58. PMID15167691.
Zill P, Büttner A, Eisenmenger W, Möller HJ, Bondy B, Ackenheil M (Oct 2004). "Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene in suicide victims". Biological Psychiatry. 56 (8): 581–6. doi:10.1016/j.biopsych.2004.07.015. PMID15476687.
Zhang X, Gainetdinov RR, Beaulieu JM, Sotnikova TD, Burch LH, Williams RB, Schwartz DA, Krishnan KR, Caron MG (Jan 2005). "Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression". Neuron. 45 (1): 11–6. doi:10.1016/j.neuron.2004.12.014. PMID15629698.
Coon H, Dunn D, Lainhart J, Miller J, Hamil C, Battaglia A, Tancredi R, Leppert MF, Weiss R, McMahon W (May 2005). "Possible association between autism and variants in the brain-expressed tryptophan hydroxylase gene (TPH2)". American Journal of Medical Genetics Part B. 135B (1): 42–6. doi:10.1002/ajmg.b.30168. PMID15768392.
Shamir A, Shaltiel G, Levi I, Belmaker RH, Agam G (2005). "Postmortem parietal cortex TPH2 expression is not altered in schizophrenic, unipolar-depressed, and bipolar patients vs control subjects". Journal of Molecular Neuroscience. 26 (1): 33–7. doi:10.1385/JMN:26:1:033. PMID15968084.
Canli T, Congdon E, Gutknecht L, Constable RT, Lesch KP (Nov 2005). "Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation". Journal of Neural Transmission. 112 (11): 1479–85. doi:10.1007/s00702-005-0391-4. PMID16245070.
Mössner R, Freitag CM, Gutknecht L, Reif A, Tauber R, Franke P, Fritze J, Wagner G, Peikert G, Wenda B, Sand P, Rietschel M, Garritsen H, Jacob C, Lesch KP, Deckert J (Jul 2006). "The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder". Journal of Psychopharmacology. 20 (4): 547–52. doi:10.1177/0269881106059704. PMID16401665.
De Luca V, Hlousek D, Likhodi O, Van Tol HH, Kennedy JL, Wong AH (Feb 2006). "The interaction between TPH2 promoter haplotypes and clinical-demographic risk factors in suicide victims with major psychoses". Genes, Brain, and Behavior. 5 (1): 107–10. doi:10.1111/j.1601-183X.2005.00182.x. PMID16436194.