IUBMB Enzyme Nomenclature


Accepted name: phenylalanine 4-monooxygenase

Reaction: L-phenylalanine + a 5,6,7,8-tetrahydropteridine + O2 = L-tyrosine + a 4a-hydroxy-5,6,7,8-tetrahydropteridine

For diagram of reactions, click here, or click here or click here

Other name(s): phenylalaninase; phenylalanine 4-hydroxylase; phenylalanine hydroxylase

Systematic name: L-phenylalanine,tetrahydropteridine:oxygen oxidoreductase (4-hydroxylating)

Comments: The active centre contains mononuclear iron(II). The reaction involves an arene oxide that rearranges to give the phenolic hydroxy group. This results in the hydrogen at C-4 migrating to C-3 and in part being retained. This process is known as the NIH-shift. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9029-73-6


1. Guroff, G. and Rhoads, C.A. Phenylalanine hydroxylation by Pseudomonas species (ATCC 11299a). Nature of the cofactor. J. Biol. Chem. 244 (1969) 142-146. [PMID: 5773277]

2. Kaufman, S. Studies on the mechanism of the enzymic conversion of phenylalanine to tyrosine. J. Biol. Chem. 234 (1959) 2677-2682. [PMID: 14404870]

3. Mitoma, C. Studies on partially purified phenylalanine hydroxylase. Arch. Biochem. Biophys. 60 (1956) 476-484. [PMID: 13292928]

4. Udenfriend, S. and Cooper, J.R. The enzymic conversion of phenylalanine to tyrosine. J. Biol. Chem. 194 (1952) 503-511. [PMID: 14927641]

5. Carr, R.T., Balasubramanian, S., Hawkins, P.C. and Benkovic, S.J. Mechanism of metal-independent hydroxylation by Chromobacterium violaceum phenylalanine hydroxylase. Biochemistry 34 (1995) 7525-7532. [PMID: 7779797]

6. Andersen, O.A., Flatmark, T. and Hough, E. High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. J. Mol. Biol. 314 (2001) 266-278. [PMID: 11718561]

7. Erlandsen, H., Kim, J.Y., Patch, M.G., Han, A., Volner, A., Abu-Omar, M.M. and Stevens, R.C. Structural comparison of bacterial and human iron-dependent phenylalanine hydroxylases: similar fold, different stability and reaction rates. J. Mol. Biol. 320 (2002) 645-661. [PMID: 12096915]

[EC created 1961 as EC, transferred 1965 to EC, transferred 1972 to EC, modified 2002, modified 2003, modified 2019]

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