Tryptophan hydroxylase

protein
Name= tryptophan hydroxylase 1 (tryptophan 5-monooxygenase)
caption=


width=
HGNCid=12008
Symbol=TPH1
AltSymbols=TPRH, TPH
EntrezGene=7166
OMIM=191060
RefSeq=NM_004179
UniProt=P17752
PDB=
ECnumber=1.14.16.4
Chromosome=11
Arm=p
Band=15.3
LocusSupplementaryData=-p14protein
Name=tryptophan hydroxylase 2
caption=


width=
HGNCid=20692
Symbol=TPH2
AltSymbols=
EntrezGene=121278
OMIM=607478
RefSeq=NM_173353
UniProt=Q8IWU9
PDB=
ECnumber=
Chromosome=12
Arm=q
Band=15
LocusSupplementaryData=

Tryptophan hydroxylase (TPH) is an enzyme (EC number|1.14.16.4) involved in the synthesis of the neurotransmitter serotonin.

Function

It is responsible for addition of the -HO group (hydroxylation) to the 5 position to form the amino acid 5-hydroxytryptophan (5-HTP), which is the initial and rate-limiting step in the synthesis of the neurotransmitter serotonin. It is also the first enzyme in the synthesis of melatonin.

Tryptophan hydroxylase (TPH), tyrosine hydroxylase (TH) and phenylalanine hydroxylase (PAH) are members of a superfamily of aromatic amino acid hydroxylases, catalyzing key steps in important metabolic pathways [http://www.bh4.org/pdf/mckinney.pdf] Analogously to phenylalanine hydroxylase and tyrosine hydroxylase, this enzyme uses (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH₄) and dioxygen as cofactors. [ [http://www.bh4.org/BH4_Deficiency_Biochemistry.asp BH4 Databases ] ]

In humans, the stimulation of serotonin production by administration of tryptophan has an antidepressant effect and inhibition of tryptophan hydroxylase (e.g. by p-Chlorophenylalanine) may precipitate depression. [ [http://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/2002/41/i42/abs/bi026561f.html Three-Dimensional Structure of Human Tryptophan Hydroxylase and Its Implications for the Biosynthesis of the Neurotransmitters Serotonin and Melatonin ] ]

The activity of tryptophan hydroxylase (i.e. the rate at which it converts L-tryptophan into the serotonin precursor L-5-hydroxytryptophan) can be increased when it undergoes phosphorylation. Protein Kinase A, for example, can phosphorylate tryptophan hydroxylase, thus increasing its activity.

Isoforms

In humans, as well as in other mammals, there are two distinct TPH genes. In humans, these genes are located on chromosomes 11 and 12 and encode two different homologous enzymes TPH1 and TPH2 (sequence identity 71%). [ [http://www.ncbi.nlm.nih.gov/pubmed/14563478 A unique central tryptophan hydroxylase isoform. [Biochem Pharmacol. 2003 - PubMed Result ] ]

* TPH1 is mostly expressed in tissues that express serotonin (a neurotransmitter) in the periphery (skin, gut, pineal gland) but it is also expressed in the central nervous system.
* On the other hand, TPH2 is exclusively expressed in neuronal cell types and is the predominant isoform in the central nervous system.

**TPH may be found in foods such as fresh fruits and fresh vegetables as well as dark chocolate (natural cocoa)**

=Additional

References

External links

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