Tryptophanhydroxylase

• OMIM: 191060
• UniProt: P17752
• MGI: 98796

Tryptophan hydroxylase (TPH ) is the name for enzymes that convert the amino acid L- tryptophan in the amino acid 5-hydroxytryptophan. This process is essential for the biosynthesis of serotonin in all chordates. Man has in addition two isoforms of the enzyme TPH1, which are formed in several tissues of the body, a second variant of TPH2, which was detected only in the brain. There are studies that show a possible link between the absence of TPH2 and ADHD and depression. Tryptophanhydroxylasen include the Phenylalaninhydroxylasen (PAH ) and tyrosine hydroxylases ( TYH ) to a group of enzymes with the cofactor biopterin, which hydroxylate aromatic amino acids.

Biosynthesis

TPH1

TPH1 is formed mainly in cells of the lung, raphe nuclei, and the pineal gland, mast cells, monocytes, lymphocytes, the beta cells of the islets of Langerhans, and intestinal and pancreatic enterochromaffin cells. TPH1 the gene is located on chromosome 11 and extends across exons 10 and 19,700 base pairs. After transcription in the 1335 bases long mRNA is produced by translation of the 444 -amino acid end product.

TPH2

TPH2 is formed in the brain, the TPH2 gene is located on chromosome 12 and spans 11 exons and 93,600 base pairs. The transcript is of a length of 2360 bases and 490 amino acids of the enzyme.

TPH2 is formed by alternative splicing in two different isoforms as TPH2a and TPH2b from the same gene in the brain. There is evidence that the ratio of TPH2a and TPH2b could be involved in the pathogenesis of psychiatric disorders, as the TPH2b a higher enzyme activity shows as TPH2a. Patients with schizophrenia showed an increased and reduced expression of TPH2b found in suicide victims.