TPH2
The enzyme Tryptophan hydroxylase 2, also known as 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,[1] 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.[2]
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][3]
See also
References
- ↑ Walther DJ, Peter JU, Bashammakh S et al. (2003). "Synthesis of serotonin by a second tryptophan hydroxylase isoform.". Science 299 (5603): 76. doi:10.1126/science.1078197. PMID 12511643.
- ↑ Zill P, Buttner A, Eisenmenger W et al. (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.
- ↑ "Entrez Gene: TPH2 tryptophan hydroxylase 2".
Further reading
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Walther DJ, Peter JU, Bashammakh S et al. (2003). "Synthesis of serotonin by a second tryptophan hydroxylase isoform.". Science 299 (5603): 76. doi:10.1126/science.1078197. PMID 12511643.
- Walther DJ, Bader M (2003). "A unique central tryptophan hydroxylase isoform.". Biochem. Pharmacol. 66 (9): 1673–80. doi:10.1016/S0006-2952(03)00556-2. PMID 14563478.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Zill P, Baghai TC, Zwanzger P et al. (2005). "SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression.". Mol. Psychiatry 9 (11): 1030–6. doi:10.1038/sj.mp.4001525. PMID 15124006.
- Breidenthal SE, White DJ, Glatt CE (2005). "Identification of genetic variants in the neuronal form of tryptophan hydroxylase (TPH2).". Psychiatr. Genet. 14 (2): 69–72. doi:10.1097/01.ypg.0000107929.32051.58. PMID 15167691.
- De Luca V, Mueller DJ, Tharmalingam S et al. (2005). "Analysis of the novel TPH2 gene in bipolar disorder and suicidality.". Mol. Psychiatry 9 (10): 896–7. doi:10.1038/sj.mp.4001531. PMID 15197398.
- Harvey M, Shink E, Tremblay M et al. (2005). "Support for the involvement of TPH2 gene in affective disorders.". Mol. Psychiatry 9 (11): 980–1. doi:10.1038/sj.mp.4001557. PMID 15263906.
- Zill P, Büttner A, Eisenmenger W et al. (2005). "Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene in suicide victims.". Biol. Psychiatry 56 (8): 581–6. doi:10.1016/j.biopsych.2004.07.015. PMID 15476687.
- Zhang X, Gainetdinov RR, Beaulieu JM et al. (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. PMID 15629698.
- Coon H, Dunn D, Lainhart J et al. (2005). "Possible association between autism and variants in the brain-expressed tryptophan hydroxylase gene (TPH2).". Am. J. Med. Genet. B Neuropsychiatr. Genet. 135 (1): 42–6. doi:10.1002/ajmg.b.30168. PMID 15768392.
- Sheehan K, Lowe N, Kirley A et al. (2005). "Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD.". Mol. Psychiatry 10 (10): 944–9. doi:10.1038/sj.mp.4001698. PMID 15940290.
- Shamir A, Shaltiel G, Levi I et al. (2005). "Postmortem parietal cortex TPH2 expression is not altered in schizophrenic, unipolar-depressed, and bipolar patients vs control subjects.". J. Mol. Neurosci. 26 (1): 33–7. doi:10.1385/JMN:26:1:033. PMID 15968084.
- Brown SM, Peet E, Manuck SB et al. (2005). "A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity.". Mol. Psychiatry 10 (9): 884–8, 805. doi:10.1038/sj.mp.4001716. PMID 16044172.
- Walitza S, Renner TJ, Dempfle A et al. (2006). "Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder.". Mol. Psychiatry 10 (12): 1126–32. doi:10.1038/sj.mp.4001734. PMID 16116490.
- Canli T, Congdon E, Gutknecht L et al. (2006). "Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation.". Journal of neural transmission (Vienna, Austria : 1996) 112 (11): 1479–85. doi:10.1007/s00702-005-0391-4. PMID 16245070.
- Mössner R, Freitag CM, Gutknecht L et al. (2006). "The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder.". J. Psychopharmacol. (Oxford) 20 (4): 547–52. doi:10.1177/0269881106059704. PMID 16401665.
- De Luca V, Hlousek D, Likhodi O et al. (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. PMID 16436194.
- Delorme R, Durand CM, Betancur C et al. (2006). "No human tryptophan hydroxylase-2 gene R441H mutation in a large cohort of psychiatric patients and control subjects.". Biol. Psychiatry 60 (2): 202–3. doi:10.1016/j.biopsych.2005.12.014. PMID 16581035.
- Carkaci-Salli N, Flanagan JM, Martz MK et al. (2006). "Functional domains of human tryptophan hydroxylase 2 (hTPH2).". J. Biol. Chem. 281 (38): 28105–12. doi:10.1074/jbc.M602817200. PMID 16864580.