Tryptophan hydroxylase

tryptophan 5-monooxygenase
tryptophan 5-monooxygenase monomer, Human
Identifiers
EC no.	1.14.16.4
CAS no.	9037-21-2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

tryptophan hydroxylase 1 (tryptophan 5-monooxygenase)
Identifiers
Symbol	TPH1
Alt. symbols	TPRH, TPH
NCBI gene	7166
HGNC	12008
OMIM	191060
PDB	1MLW
RefSeq	NM_004179
UniProt	P17752
Other data
EC number	1.14.16.4
Locus	Chr. 11 p15.3-p14
Search for Structures Swiss-model Domains InterPro

tryptophan hydroxylase 2
Identifiers
Symbol	TPH2
NCBI gene	121278
HGNC	20692
OMIM	607478
RefSeq	NM_173353
UniProt	Q8IWU9
Other data
Locus	Chr. 12 q15
Search for Structures Swiss-model Domains InterPro

Tryptophan hydroxylase (TPH) is an enzyme (EC 1.14.16.4) involved in the synthesis of the monoamine neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-dependent aromatic amino acid hydroxylases. TPH catalyzes the following chemical reaction

L-tryptophan + tetrahydrobiopterin + O₂ ${\displaystyle \rightleftharpoons }$ 5-Hydroxytryptophan + dihydrobiopterin + H₂O

It employs one additional cofactor, iron.

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 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.^[1] Analogously to phenylalanine hydroxylase and tyrosine hydroxylase, this enzyme uses (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH₄) and dioxygen as cofactors.^[2]

In humans, the stimulation of serotonin production by administration of tryptophan has an antidepressant effect^[3][4] and inhibition of tryptophan hydroxylase (e.g. by p-Chlorophenylalanine) may precipitate depression.^[5]

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.

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%).^[6]

• 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.

• 
  The pathway for the synthesis of serotonin from tryptophan
• 
  Metabolic pathway from tryptophan to serotonin

• Biology portal

• Tryptophan+Hydroxylase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• See also tryptophan hydroxylase in Proteopedia