Tryptophan hydroxylase (TPH) is an
enzyme () involved in the synthesis of the neurotransmitter
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
.
Tyrosine hydroxylase,
phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-dependent
aromatic amino acid hydroxylase
Biopterin-dependent aromatic amino acid hydroxylases (AAAH) are a family of aromatic amino acid hydroxylase enzymes which includes phenylalanine 4-hydroxylase (), tyrosine 3-hydroxylase (), and tryptophan 5-hydroxylase (). These enzymes primaril ...
s. TPH catalyzes the following chemical reaction
: L-
tryptophan +
tetrahydrobiopterin + O
2 5-Hydroxytryptophan
5-Hydroxytryptophan (5-HTP), also known as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin.
Uses
5-HTP is sold over the counter i ...
+
dihydrobiopterin + H
2O
It employs one additional
cofactor,
iron.
Function
It is responsible for addition of the -OH group (
hydroxylation
In chemistry, hydroxylation can refer to:
*(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound.
*(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...
) to the 5 position to form the
amino acid 5-hydroxytryptophan
5-Hydroxytryptophan (5-HTP), also known as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin.
Uses
5-HTP is sold over the counter i ...
(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 hydroxylase
Biopterin-dependent aromatic amino acid hydroxylases (AAAH) are a family of aromatic amino acid hydroxylase enzymes which includes phenylalanine 4-hydroxylase (), tyrosine 3-hydroxylase (), and tryptophan 5-hydroxylase (). These enzymes primaril ...
s, catalyzing key steps in important metabolic pathways.
Analogously to
phenylalanine hydroxylase and
tyrosine hydroxylase, this enzyme uses (6R)-L-erythro-5,6,7,8-
tetrahydrobiopterin (BH
4) and dioxygen as cofactors.
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
Fenclonine, also known as ''para''-chlorophenylalanine (PCPA), acts as a selective and irreversible inhibitor of tryptophan hydroxylase, which is a rate-limiting enzyme in the biosynthesis of serotonin.
It has been used experimentally to treat c ...
) may precipitate depression.
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
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
.
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
Tryptophan hydroxylase 2 (TPH2) is an isozyme of tryptophan hydroxylase found in vertebrates. In humans, TPH2 is primarily expressed in the serotonergic neurons of the brain, with the highest expression in the raphe nucleus of the midbrain. Until ...
'' (sequence identity 71%).
*TPH1 is mostly expressed in tissues that express serotonin (a neurotransmitter) in the periphery (
skin,
gut,
pineal gland
The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep, sleep patterns in both circadian rhythm, circ ...
) 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 images
Image:5htsynt 2.png , The pathway for the synthesis of serotonin from tryptophan
Image:Trp-5ht-pathway.svg , Metabolic pathway from tryptophan to serotonin
See also
*
References
Further reading
*
*
*
*
*
*
External links
*
* See als
tryptophan hydroxylasei
Proteopedia
EC 1.14.16
{{1.14-enzyme-stub