Tryptophan hydroxylase

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Tryptophan hydroxylase 1
Tryptophan hydroxylase 1
with Biopterin and Fe 3+ according to PDB  1MLW

Existing structural data : 1in9 , 1mlw

Properties of human protein
Mass / length primary structure 444 amino acids; 51 kDa
Cofactor Biopterin, Fe 3+
Isoforms 2
Identifier
Gene names TPH1  ; TPRH, TPH
External IDs
Enzyme classification
EC, category 1.14.16.4 dioxygenase
Response type Hydroxylation
Substrate L-tryptophan + tetrahydrobiopterin + O 2
Products 5-Hydroxytryptophan + 4a-Hydroxytetrahydrobiopterin
Occurrence
Homology family Tyrosine hydroxylase
Parent taxon Chordates

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

biosynthesis

TPH1

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

TPH2

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

TPH2 is formed in the brain by alternative splicing in two different isoforms as TPH2a and TPH2b from the same gene. There are indications that the ratio of TPH2a and TPH2b could be involved in the development of psychiatric illnesses, since the TPH2b shows a higher enzyme activity than TPH2a. An increased expression of TPH2b was found in schizophrenia patients and a reduced expression in suicide victims.

Individual evidence

  1. UniProt P17752 .
  2. a b tryptophan hydroxylase.  In: Online Mendelian Inheritance in Man . (English).
  3. Swiss Institute of Bioinformatics (SIB): PROSITE documentation PDOC00316. Tetrahydrobiopterin-dependent aromatic amino acid hydroxylase family. Retrieved August 12, 2011 .
  4. ENSEMBL entry TPH1
  5. ENSEMBL entry TPH2
  6. The role of tryptophan hydroxylase 2 in the development of psychiatric diseases (PDF; 5.4 MB)

Web links