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. Analogously to
phenylalanine hydroxylase and
tyrosine hydroxylase, this enzyme uses (6
R)--erythro-5,6,7,8-
tetrahydrobiopterin (BH4) 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) may precipitate depression. The
activity of tryptophan hydroxylase (i.e., the rate at which it converts -tryptophan into the serotonin precursor -5-hydroxytryptophan) can be increased when it undergoes
phosphorylation.
Protein Kinase A, for example, can phosphorylate tryptophan hydroxylase, thus increasing its activity. == Isoforms ==