Tryptophan hydroxylase

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tryptophan 5-monooxygenase
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MetaCycmetabolic pathway
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Chr. 11 p15.3-p14
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Tryptophan hydroxylase (TPH) is an

aromatic amino acid hydroxylases
. TPH catalyzes the following chemical reaction

L-tryptophan + tetrahydrobiopterin + O2 5-Hydroxytryptophan + dihydrobiopterin + H2O

It employs one additional cofactor, iron.

Function

It is responsible for addition of the -OH group (

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),

aromatic amino acid hydroxylases, catalyzing key steps in important metabolic pathways.[1] Analogously to phenylalanine hydroxylase and tyrosine hydroxylase, this enzyme uses (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) and dioxygen as cofactors.[2]

In humans, the stimulation of serotonin production by administration of tryptophan has an antidepressant effect

p-Chlorophenylalanine) may precipitate depression.[5]

The

Protein Kinase A
, for example, can phosphorylate tryptophan hydroxylase, thus increasing its activity.

Isoforms

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%).[6]

Additional images

  • The pathway for the synthesis of serotonin from tryptophan
    The pathway for the synthesis of serotonin from tryptophan
  • Metabolic pathway from tryptophan to serotonin
    Metabolic pathway from tryptophan to serotonin

See also

References

  1. PMID 11747434. Archived from the original
    (PDF) on 2008-12-17.
  2. ^ "tetrahydrobiopterin". BH4 Databases. BH4.org. 2005. Archived from the original on 2006-12-06.
  3. PMID 25858202
    .
  4. .
  5. .
  6. .

Further reading

External links