Biology:TPH1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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

TPH1 was first discovered to support serotonin synthesis in 1988 by converting tryptophan into 5-hydroxytryptophan.[2] 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.[3]

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.[1][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.[3] 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,[4] while a case-control study (2001) could find no association between polymorphisms and Alzheimer's disease.[5]

One human mutant of TPH1, A218C found in intron 7, is highly associated with schizophrenia.[6] 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. 1.0 1.1 "Entrez Gene: TPH1 tryptophan hydroxylase 1 (tryptophan 5-monooxygenase)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7166. 
  2. "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. December 1988. doi:10.1089/jir.1988.8.705. PMID 3148005. 
  3. 3.0 3.1 "Synthesis of serotonin by a second tryptophan hydroxylase isoform". Science 299 (5603): 76. January 2003. doi:10.1126/science.1078197. PMID 12511643. 
  4. "Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: a preliminary study". Am. J. Med. Genet. 81 (1): 13–7. 1998. doi:10.1002/(SICI)1096-8628(19980207)81:1<13::AID-AJMG3>3.0.CO;2-O. PMID 9514581. 
  5. "No association between tryptophan hydroxylase gene polymorphism and Alzheimer's disease". Neuropsychobiology 43 (1): 1–4. January 2001. doi:10.1159/000054856. PMID 11150890. 
  6. "Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database". Nat. Genet. 40 (7): 827–34. July 2008. doi:10.1038/ng.171. PMID 18583979. 

Further reading

External links

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