Amino acid hydroxylases | Enzymes | IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY

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Amino acid hydroxylases

Amino acid hydroxylases C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The amino acid hydroxylases (monooxygenases), EC.1.14.16.-, are iron-containing enzymes which utilise molecular oxygen and sapropterin as co-substrate and co-factor, respectively. In humans, as well as in other mammals, there are two distinct L-Tryptophan hydroxylase 2 genes. In humans, these genes are located on chromosomes 11 and 12 and encode two different homologous enzymes, TPH1 and TPH2.

Enzymes

Targets of relevance to immunopharmacology are highlighted in blue

L-Phenylalanine hydroxylase C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

1240

Nomenclature

L-Phenylalanine hydroxylase

Previous and unofficial names

Phenylalanine 4-monooxygenase | PH | phe-4-monooxygenase | phenylalanine-4-hydroxylase

Genes

PAH (Hs), Pah (Mm), Pah (Rn)

Ensembl ID

ENSG00000171759 (Hs), ENSMUSG00000020051 (Mm), ENSRNOG00000004302 (Rn)

UniProtKB AC

P00439 (Hs), P16331 (Mm), P04176 (Rn)

EC number

1.14.16.1

L-phenylalanine + O₂ -> L-tyrosine

Endogenous activators (Rat)

Protein kinase A-mediated phosphorylation [1]

Endogenous substrates

L-phenylalanine

Products

L-tyrosine

Cofactors

sapropterin

Selective inhibitors

α-methylphenylalanine [5] - Rat

fenclonine

Comment

PAH is an iron bound homodimer or -tetramer from the same structural family as tyrosine 3-monooxygenase and the tryptophan hydroxylases. Deficiency or loss-of-function of PAH is associated with phenylketonuria

L-Tyrosine hydroxylase C Show summary »« Hide summary More detailed page go icon to follow link

L-Tryptophan hydroxylase 1 C Show summary »« Hide summary

L-Tryptophan hydroxylase 2 C Show summary »« Hide summary

References

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1. Abita JP, Milstien S, Chang N, Kaufman S. (1976) In vitro activation of rat liver phenylalanine hydroxylase by phosphorylation. J Biol Chem, 251 (17): 5310-4. [PMID:182695]

2. Bae EJ, Choi WG, Pagire HS, Pagire SH, Parameswaran S, Choi JH, Yoon J, Choi WI, Lee JH, Song JS et al.. (2021) Peripheral Selective Oxadiazolylphenyl Alanine Derivatives as Tryptophan Hydroxylase 1 Inhibitors for Obesity and Fatty Liver Disease. J Med Chem, 64 (2): 1037-1053. [PMID:33417443]

3. Daubner SC, Le T, Wang S. (2011) Tyrosine hydroxylase and regulation of dopamine synthesis. Arch Biochem Biophys, 508 (1): 1-12. [PMID:21176768]

4. Goldberg DR, De Lombaert S, Aiello R, Bourassa P, Barucci N, Zhang Q, Paralkar V, Stein AJ, Holt M, Valentine J et al.. (2017) Optimization of spirocyclic proline tryptophan hydroxylase-1 inhibitors. Bioorg Med Chem Lett, 27 (3): 413-419. [PMID:28041831]

5. Greengard O, Yoss MS, Del Valle JA. (1976) Alpha-methylphenylalanine, a new inducer of chronic hyperphenylalaninemia in sucling rats. Science, 192 (4243): 1007-8. [PMID:944951]

6. Joh TH, Park DH, Reis DJ. (1978) Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation. Proc Natl Acad Sci USA, 75 (10): 4744-8. [PMID:33381]

7. Johansen PA, Jennings I, Cotton RG, Kuhn DM. (1996) Phosphorylation and activation of tryptophan hydroxylase by exogenous protein kinase A. J Neurochem, 66 (2): 817-23. [PMID:8592157]

8. Kim JJ, Wang H, Terc JD, Zambrowicz B, Yang QM, Khan WI. (2015) Blocking peripheral serotonin synthesis by telotristat etiprate (LX1032/LX1606) reduces severity of both chemical- and infection-induced intestinal inflammation. Am J Physiol Gastrointest Liver Physiol, 309 (6): G455-65. [PMID:26206858]

9. Nicholson AN, Wright CM. (1981) (+)-6-fluorotryptophan, an inhibitor of tryptophan hydroxylase: sleep and wakefulness in the rat. Neuropharmacology, 20 (4): 335-9. [PMID:6457252]

10. Specker E, Wesolowski R, Schutz A, Matthes S, Mallow K, Wasinska-Kalwa M, Winkleer L, Oder A, Alenina N, Pleimes D et al.. (2023) Structure-Based Design of Xanthine-Imidazopyridines and -Imidazothiazoles as Highly Potent and In Vivo Efficacious Tryptophan Hydroxylase Inhibitors. J Med Chem, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.3c01454

How to cite this family page

Database page citation:

Amino acid hydroxylases. Accessed on 23/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=249.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.