Reaction: L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin
For diagram click here and here.
Glossary: L-dopa = 3,4-dihydroxy-L-phenylalanine
Other name(s): L-tyrosine hydroxylase; tyrosine 3-hydroxylase; tyrosine hydroxylase
Systematic name: L-tyrosine,tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating)
Comments: The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by EC 22.214.171.124, [acetyl-CoA caboxylase]kinase. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 126.96.36.199, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 188.8.131.52 (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9036-22-0
1. El Mestikawy, S., Glowinski, J. and Hamon, M. Tyrosine hydroxylase activation in depolarized dopaminergic terminals -involvement of Ca2+-dependent phosphorylation. Nature (Lond.) 302 (1983) 830-832. [PMID: 6133218]
2. Ikeda, M., Levitt, M. and Udenfriend, S. Phenylalanine as substrate and inhibitor of tyrosine hydroxylase. Arch. Biochem. Biophys. 120 (1967) 420-427. [PMID: 6033458]
3. Nagatsu, T., Levitt, M. and Udenfriend, S. Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J. Biol. Chem. 239 (1964) 2910-2917.
4. Pigeon, D., Drissi-Daoudi, R., Gros, F. and Thibault, J. Copurification of tyrosine-hydroxylase from rat pheochromocytoma, with a protein-kinase activity. C.R. Acad. Sci. Paris, Ser. 3, 302 (1986) 435-438. [PMID: 2872947]
5. Goodwill, K.E., Sabatier, C., Marks, C., Raag, R., Fitzpatrick, P.F. and Stevens, R.C. Crystal structure of tyrosine hydroxylase at 2.3 Å and its implications for inherited neurodegenerative diseases. Nat. Struct. Biol. 4 (1997) 578-585. [PMID: 9228951]