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Tryptophan hydroxylase

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tryptophan hydroxylase 1 (tryptophan 5-monooxygenase)
Symbol(s): TPH1 TPRH, TPH
Locus: 11 p15.3 -p14
EC number 1.14.16.4
EntrezGene 7166
OMIM 191060
RefSeq NM_004179
UniProt P17752
tryptophan hydroxylase 2
Symbol(s): TPH2
Locus: 12 q15
EC number [1]
EntrezGene 121278
OMIM 607478
RefSeq NM_173353
UniProt Q8IWU9

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

FunctionEdit

It is responsible for addition of the -OH group (hydroxylation) to the 5 position to form the amino acid 5-hydroxytryptophan (5-HTP), which is then converted to serotonin by decarboxylation:

Analogous to phenylalanine hydroxylase and tyrosine hydroxylase, this enzyme uses tetrahydrobiopterin as a co-substrate.[1]

Tryptophan can cross the Blood-brain barrier, while Serotonin cannot. For this reason, tryptophan is administered when the desired effect is to have larger amounts of serotonin in the brain.

The "activity" of tryptophan hydroxylase (i.e. the rate 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. This phosphorylation is of particular interest, because in the 2 major steps to serotonin production (L-tryptophan to L-5-hydroxytryptophan to 5-hydroxytryptamine [serotonin]), the first step - involving tryptophan hydroxylase - is the rate limiting step.

IsoformsEdit

In humans, as well as in other mammals, there are two isoforms of this enzyme. These isoforms are termed 1 and 2 and derive from two different, but homologous, genes.

  • TPH1 is mostly expressed in tissues that express serotonin 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.

Additional imagesEdit

ReferencesEdit

  1. http://www.bh4.org/BH4_Deficiency_Biochemistry.asp

External linksEdit

  1. REDIRECT Template:Dioxygenases


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