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.
^Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC (Oct 2002). "Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin". Biochemistry41 (42): 12569–74. doi:10.1021/bi026561f. PMID12379098.
Friedman PA, Kappelman AH, Kaufman S (Jul 1972). "Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain". The Journal of Biological Chemistry247 (13): 4165–73. PMID4402511.
Hamon M, Bourgoin S, Artaud F, Glowinski J (Nov 1979). "The role of intraneuronal 5-HT and of tryptophan hydroxylase activation in the control of 5-HT synthesis in rat brain slices incubated in K+-enriched medium". Journal of Neurochemistry33 (5): 1031–42. doi:10.1111/j.1471-4159.1979.tb05239.x. PMID315449.
Ichiyama A, Nakamura S, Nishizuka Y, Hayaishi O (Apr 1970). "Enzymic studies on the biosynthesis of serotonin in mammalian brain". The Journal of Biological Chemistry245 (7): 1699–709. PMID5309585.
Jequier E, Robinson DS, Lovenberg W, Sjoerdsma A (May 1969). "Further studies on tryptophan hydroxylase in rat brainstem and beef pineal". Biochemical Pharmacology18 (5): 1071–81. doi:10.1016/0006-2952(69)90111-7. PMID5789774.
Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC (Oct 2002). "Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin". Biochemistry41 (42): 12569–74. doi:10.1021/bi026561f. PMID12379098.
Windahl MS, Petersen CR, Christensen HE, Harris P (Nov 2008). "Crystal structure of tryptophan hydroxylase with bound amino acid substrate". Biochemistry47 (46): 12087–94. doi:10.1021/bi8015263. PMID18937498.