TPH1

TPH1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTPH1, TPRH, TRPH, tryptophan hydroxylase 1
External IDsOMIM: 191060; MGI: 98796; HomoloGene: 121565; GeneCards: TPH1; OMA:TPH1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

7166

21990

Ensembl

ENSG00000129167

ENSMUSG00000040046

UniProt

P17752

P17532

RefSeq (mRNA)

NM_004179

NM_001136084
NM_001276372
NM_009414

RefSeq (protein)

NP_004170

NP_001129556
NP_001263301
NP_033440

Location (UCSC)Chr 11: 18.02 – 18.05 MbChr 7: 46.29 – 46.32 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Tryptophan hydroxylase 1 (TPH1) is an isoenzyme of tryptophan hydroxylase which in humans is encoded by the TPH1 gene.[5]

TPH1 was first discovered to support serotonin synthesis in 1988 by converting tryptophan into 5-hydroxytryptophan.[6] It was thought that there only was a single TPH gene until 2003. A second form was found in the mouse (Tph2), rat and human brain (TPH2) and the original TPH was then renamed to TPH1.[7]

Function

Tryptophan hydroxylases catalyze the biopterin-dependent monooxygenation of tryptophan to 5-hydroxytryptophan (5-HTP), which is subsequently decarboxylated by aromatic amino acid decarboxylase to form the neurotransmitter serotonin (5-hydroxytryptamine or 5-HT). It is the rate-limiting enzyme in the biosynthesis of serotonin.

TPH expression is limited to a few specialized tissues: raphe neurons, pinealocytes, mast cells, mononuclear leukocytes, beta-cells of the islets of Langerhans, and intestinal and pancreatic enterochromaffin cells.[5][citation needed]

Clinical significance

Tryptophan hydroxylase is important for synthesizing indoleamine neurotransmitters and related compounds in the body and brain, including serotonin and melatonin. TPH1 is expressed in the body, but not the brain.[7] Nevertheless, the effect of variations in the TPH1 gene on brain-related variables, such as personality traits and neuropsychiatric disorders, has been studied. For example, one study (1998) found an association between a polymorphism in the gene with impulsive-aggression measures,[8] while a case-control study (2001) could find no association between polymorphisms and Alzheimer's disease.[9]

One human mutant of TPH1, A218C found in intron 7, is highly associated with schizophrenia.[10] Introns are regions of DNA that do not code for the amino acid sequence of a protein and were long considered to be 'junk DNA' lacking purpose. The correlation of an intron mutation with schizophrenia is significant because it suggests that introns have an important role in translation, transcription, or another, possibly unknown, aspect of the production of proteins from DNA.

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000129167 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040046 – 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. ^ a b "Entrez Gene: TPH1 tryptophan hydroxylase 1 (tryptophan 5-monooxygenase)".
  6. ^ Finocchiaro LM, Arzt ES, Fernández-Castelo S, Criscuolo M, Finkielman S, Nahmod VE (December 1988). "Serotonin and melatonin synthesis in peripheral blood mononuclear cells: stimulation by interferon-gamma as part of an immunomodulatory pathway". J. Interferon Res. 8 (6): 705–16. doi:10.1089/jir.1988.8.705. PMID 3148005.
  7. ^ a b 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.
  8. ^ New AS, Gelernter J, Yovell Y, Trestman RL, Nielsen DA, Silverman J, Mitropoulou V, Siever LJ (1998). "Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: a preliminary study". Am. J. Med. Genet. 81 (1): 13–7. doi:10.1002/(SICI)1096-8628(19980207)81:1<13::AID-AJMG3>3.0.CO;2-O. PMID 9514581.
  9. ^ Wang YC, Tsai SJ, Liu TY, Liu HC, Hong CJ (January 2001). "No association between tryptophan hydroxylase gene polymorphism and Alzheimer's disease". Neuropsychobiology. 43 (1): 1–4. doi:10.1159/000054856. PMID 11150890. S2CID 39712696.
  10. ^ Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, Khoury MJ, Tanzi RE, Bertram L (July 2008). "Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database". Nat. Genet. 40 (7): 827–34. doi:10.1038/ng.171. PMID 18583979. S2CID 21772210.

Further reading

  • Overview of all the structural information available in the PDB for UniProt: P17752 (Tryptophan 5-hydroxylase 1) at the PDBe-KB.

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