It is responsible for addition of the -HO group (hydroxylation) to the 5 position to form the amino acid5-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.
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.
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%).
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.
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