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| - | ==Tryptophan hydroxylase==
| + | #REDIRECT [[Hydroxylase]] |
| - | Tryptophan hydroxylase (TPH) (tryptophan 5-monooxygenase, EC 1.14.16.4) catalyses the reaction between tryptophan, 5,6,7,8-tetrahydrobiopterin (BH4) and O2 to give 5-hydroxytryptophan and 4a-hydroxy-tetrahydrobiopterin (4a-hydroxy-BH4. This reaction is the first and rate limiting step in the biosynthesis of serotonin (See scheme).
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| - | Together with phenylalanine hydroxylase (EC 1.14.16.1) and tyrosine hydroxylase (EC 1.14.16.2), TPH form the small enzyme family of aromatic amino acid hydroxylases (AAAH) []. These enzymes all contain iron and use BH4 as a co-substrate in the hydroxylation of their respective aromatic amino acids [ , , ]. Additionally all mammalian AAAH form homotetramers and each monomer consists of three domains. These domains are the N-terminal regulatory domain (100-150 residues), the catalytic domain (approximately 315 residues) and the C-terminal tetramerisation domain (approximately 30-40 residues) [ , , , ].
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| - | ==The two isoforms of tryptophan hydroxylase==
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| - | TPH exists in two isoforms called TPH isoform 1 (TPH1) and TPH isoform 2 (TPH2) [ ]. The existence of two isoforms was observed when TPH was purified and characterised from different tissues [ , , , , ]. The gene encoding for rabbit TPH1 was identified in 1987 by Grenett et al.[7] and a few years later the human gene for TPH1 was identified on chromosome 11 [ , ]. The gene for isoform 2 was identified in 2003 by Walther et al. and the human gene is located on chromosome 12 [19].
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| - | The two isoforms are expressed in different tissues. TPH2 is mainly expressed in serotonergic neurons of the brain and gut [19, , , , ]. TPH1 is expressed in other parts of the body such as the pineal gland [4,27], skin cells [ ], mast cells [1], intestinal mucosa and enterochromafin cells [ ] and in cancer cells [ , ]. The main difference between the two isoforms is that the N-terminal is extended by 46 residues in TPH2 (see sequence alignment in section 2.3) [ ].
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| - | {{STRUCTURE_1mlw | PDB=1mlw | SCENE= }}
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