The Enzyme Database

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EC 1.1.1.153     
Accepted name: sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
Reaction: (1) L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
(2) L-erythro-tetrahydrobiopterin + 2 NADP+ = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH + 2 H+
For diagram of biopterin biosynthesis, click here
Glossary: sepiapterin = 2-amino-6-lactoyl-7,8-dihydropteridin-4(3H)-one
tetrahydrobiopterin = 5,6,7,8-tetrahydrobiopterin = 2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydropteridin-4(3H)-one
Other name(s): SR
Systematic name: L-erythro-7,8-dihydrobiopterin:NADP+ oxidoreductase
Comments: This enzyme catalyses the final step in the de novo synthesis of tetrahydrobiopterin from GTP. The enzyme, which is found in higher animals and some fungi and bacteria, produces the erythro form of tetrahydrobiopterin. cf. EC 1.1.1.325, sepiapterin reductase (L-threo-7,8-dihydrobiopterin forming).
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9059-48-7
References:
1.  Katoh, S. Sepiapterin reductase from horse liver: purification and properties of the enzyme. Arch. Biochem. Biophys. 146 (1971) 202–214. [DOI] [PMID: 4401291]
2.  Matsubara, M., Katoh, S., Akino, M. and Kaufman, S. Sepiapterin reductase. Biochim. Biophys. Acta 122 (1966) 202–212. [PMID: 5969298]
3.  Werner, E.R., Schmid, M., Werner-Felmayer, G., Mayer, B. and Wachter, H. Synthesis and characterization of 3H-labelled tetrahydrobiopterin. Biochem. J. 304 (1994) 189–193. [PMID: 7528005]
4.  Kim, Y.A., Chung, H.J., Kim, Y.J., Choi, Y.K., Hwang, Y.K., Lee, S.W. and Park, Y.S. Characterization of recombinant Dictyostelium discoideum sepiapterin reductase expressed in E. coli. Mol. Cells 10 (2000) 405–410. [PMID: 10987137]
[EC 1.1.1.153 created 1972, modified 2012]
 
 
EC 1.1.1.220     
Accepted name: 6-pyruvoyltetrahydropterin 2′-reductase
Reaction: 6-lactoyl-5,6,7,8-tetrahydropterin + NADP+ = 6-pyruvoyltetrahydropterin + NADPH + H+
For diagram of 6-pyruvyltetrahydropterin metabolism, click here
Other name(s): 6-pyruvoyltetrahydropterin reductase; 6PPH4(2′-oxo) reductase; 6-pyruvoyl tetrahydropterin (2′-oxo)reductase; 6-pyruvoyl-tetrahydropterin 2′-reductase; pyruvoyl-tetrahydropterin reductase
Systematic name: 6-lactoyl-5,6,7,8-tetrahydropterin:NADP+ 2′-oxidoreductase
Comments: Not identical with EC 1.1.1.153 sepiapterin reductase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 97089-79-7
References:
1.  Milstien, S. and Kaufman, S. Biosynthesis of tetrahydrobiopterin: conversion of dihydroneopterin triphosphate to tetrahydropterin intermediates. Biochem. Biophys. Res. Commun. 128 (1985) 1099–1107. [DOI] [PMID: 4004850]
[EC 1.1.1.220 created 1989]
 
 
EC 1.1.1.325     
Accepted name: sepiapterin reductase (L-threo-7,8-dihydrobiopterin forming)
Reaction: (1) L-threo-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
(2) L-threo-tetrahydrobiopterin + 2 NADP+ = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH + 2 H+
Glossary: sepiapterin = 2-amino-6-lactoyl-7,8-dihydropteridin-4(3H)-one
tetrahydrobiopterin = 5,6,7,8-tetrahydrobiopterin = 2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydropteridin-4(3H)-one
Systematic name: L-threo-7,8-dihydrobiopterin:NADP+ oxidoreductase
Comments: This enzyme, isolated from the bacterium Chlorobium tepidum, catalyses the final step in the de novo synthesis of tetrahydrobiopterin from GTP. cf. EC 1.1.1.153, sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming).
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9059-48-7
References:
1.  Cho, S.H., Na, J.U., Youn, H., Hwang, C.S., Lee, C.H. and Kang, S.O. Sepiapterin reductase producing L-threo-dihydrobiopterin from Chlorobium tepidum. Biochem. J. 340 (1999) 497–503. [PMID: 10333495]
2.  Supangat, S., Choi, Y.K., Park, Y.S., Son, D., Han, C.D. and Lee, K.H. Expression, purification, crystallization and preliminary X-ray analysis of sepiapterin reductase from Chlorobium tepidum. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 (2005) 202–204. [DOI] [PMID: 16510994]
[EC 1.1.1.325 created 2012]
 
 
EC 1.5.1.33     
Accepted name: pteridine reductase
Reaction: 5,6,7,8-tetrahydrobiopterin + 2 NADP+ = biopterin + 2 NADPH + 2 H+
Other name(s): PTR1; pteridine reductase 1
Systematic name: 5,6,7,8-tetrahydrobiopterin:NADP+ oxidoreductase
Comments: The enzyme from Leishmania (both amastigote and promastigote forms) catalyses the reduction by NADPH of folate and a wide variety of unconjugated pterins, including biopterin, to their tetrahydro forms. It also catalyses the reduction of 7,8-dihydropterins and 7,8-dihydrofolate to their tetrahydro forms. In contrast to EC 1.5.1.3 (dihydrofolate reductase) and EC 1.5.1.34 (6,7-dihydropteridine reductase), pteridine reductase will not catalyse the reduction of the quinonoid form of dihydrobiopterin. The enzyme is specific for NADPH; no activity has been detected with NADH. It also differs from EC 1.5.1.3 (dihydrofolate reductase) in being specific for the Si-face of NADPH.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 131384-61-7
References:
1.  Nare, B., Hardy, L. and Beverley, S.M. The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in pteridine metabolism in the protozoan parasite Leishmania major. J. Biol. Chem. 272 (1997) 13883–13891. [DOI] [PMID: 9153248]
2.  Gourley, D.G., Schüttelkopf, A.W., Leonard, G.A., Luba, J., Hardy, L.W., Beverley, S.M. and Hunter, W.N. Pteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites. Nat. Struct. Biol. 8 (2001) 521–525. [DOI] [PMID: 11373620]
3.  Fitzpatrick, P.F. The aromatic amino acid hydroxylases. Adv. Enzymol. Relat. Areas Mol. Biol. 74 (2000) 235–294. [PMID: 10800597]
[EC 1.5.1.33 created 1999 as EC 1.1.1.253, transferred 2003 to EC 1.5.1.33]
 
 
EC 1.14.13.39     
Accepted name: nitric-oxide synthase (NADPH)
Reaction: 2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O (overall reaction)
(1a) 2 L-arginine + 2 NADPH + 2 H+ + 2 O2 = 2 Nω-hydroxy-L-arginine + 2 NADP+ + 2 H2O
(1b) 2 Nω-hydroxy-L-arginine + NADPH + H+ + 2 O2 = 2 L-citrulline + 2 nitric oxide + NADP+ + 2 H2O
Glossary: nitric oxide = NO = nitrogen(II) oxide
Other name(s): NOS (gene name); nitric oxide synthetase (ambiguous); endothelium-derived relaxation factor-forming enzyme; endothelium-derived relaxing factor synthase; NO synthase (ambiguous); NADPH-diaphorase (ambiguous)
Systematic name: L-arginine,NADPH:oxygen oxidoreductase (nitric-oxide-forming)
Comments: The enzyme consists of linked oxygenase and reductase domains. The eukaryotic enzyme binds FAD, FMN, heme (iron protoporphyrin IX) and tetrahydrobiopterin, and its two domains are linked via a regulatory calmodulin-binding domain. Upon calcium-induced calmodulin binding, the reductase and oxygenase domains form a complex, allowing electrons to flow from NADPH via FAD and FMN to the active center. The reductase domain of the enzyme from the bacterium Sorangium cellulosum utilizes a [2Fe-2S] cluster to transfer the electrons from NADPH to the active center. cf. EC 1.14.14.47, nitric-oxide synthase (flavodoxin).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 125978-95-2
References:
1.  Bredt, D.S. and Snyder, S.H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc. Natl. Acad. Sci. USA 87 (1990) 682–685. [DOI] [PMID: 1689048]
2.  Stuehr, D.J., Kwon, N.S., Nathan, C.F., Griffith, O.W., Feldman, P.L. and Wiseman, J. Nω-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine. J. Biol. Chem. 266 (1991) 6259–6263. [PMID: 1706713]
3.  Stuehr, D., Pou, S. and Rosen, G.M. Oxygen reduction by nitric-oxide synthases. J. Biol. Chem. 276 (2001) 14533–14536. [DOI] [PMID: 11279231]
4.  Agapie, T., Suseno, S., Woodward, J.J., Stoll, S., Britt, R.D. and Marletta, M.A. NO formation by a catalytically self-sufficient bacterial nitric oxide synthase from Sorangium cellulosum. Proc. Natl. Acad. Sci. USA 106 (2009) 16221–16226. [DOI] [PMID: 19805284]
5.  Foresi, N., Correa-Aragunde, N., Parisi, G., Calo, G., Salerno, G. and Lamattina, L. Characterization of a nitric oxide synthase from the plant kingdom: NO generation from the green alga Ostreococcus tauri is light irradiance and growth phase dependent. Plant Cell 22 (2010) 3816–3830. [DOI] [PMID: 21119059]
[EC 1.14.13.39 created 1992, modified 2012, modified 2017]
 
 
EC 1.14.13.165      
Transferred entry: nitric-oxide synthase [NAD(P)H]. Now classified as EC 1.14.14.47, nitric-oxide synthase (flavodoxin)
[EC 1.14.13.165 created 2012, deleted 2017]
 
 
EC 1.14.14.47     
Accepted name: nitric-oxide synthase (flavodoxin)
Reaction: 2 L-arginine + 3 reduced flavodoxin + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 oxidized flavodoxin + 4 H2O (overall reaction)
(1a) 2 L-arginine + 2 reduced flavodoxin + 2 O2 = 2 Nω-hydroxy-L-arginine + 2 oxidized flavodoxin + 2 H2O
(1b) 2 Nω-hydroxy-L-arginine + reduced flavodoxin + 2 O2 = 2 L-citrulline + 2 nitric oxide + oxidized flavodoxin + 2 H2O
Glossary: nitric oxide = NO = nitrogen(II) oxide
Other name(s): nitric oxide synthetase (ambiguous); NO synthase (ambiguous)
Systematic name: L-arginine,reduced-flavodoxin:oxygen oxidoreductase (nitric-oxide-forming)
Comments: Binds heme (iron protoporphyrin IX) and tetrahydrobiopterin. The enzyme, found in bacteria and archaea, consist of only an oxygenase domain and functions together with bacterial ferredoxins or flavodoxins. The orthologous enzymes from plants and animals also contain a reductase domain and use only NADPH as the electron donor (cf. EC 1.14.13.39).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Pant, K., Bilwes, A.M., Adak, S., Stuehr, D.J. and Crane, B.R. Structure of a nitric oxide synthase heme protein from Bacillus subtilis. Biochemistry 41 (2002) 11071–11079. [DOI] [PMID: 12220171]
2.  Adak, S., Aulak, K.S. and Stuehr, D.J. Direct evidence for nitric oxide production by a nitric-oxide synthase-like protein from Bacillus subtilis. J. Biol. Chem. 277 (2002) 16167–16171. [DOI] [PMID: 11856757]
3.  Wang, Z.Q., Lawson, R.J., Buddha, M.R., Wei, C.C., Crane, B.R., Munro, A.W. and Stuehr, D.J. Bacterial flavodoxins support nitric oxide production by Bacillus subtilis nitric-oxide synthase. J. Biol. Chem. 282 (2007) 2196–2202. [DOI] [PMID: 17127770]
4.  Agapie, T., Suseno, S., Woodward, J.J., Stoll, S., Britt, R.D. and Marletta, M.A. NO formation by a catalytically self-sufficient bacterial nitric oxide synthase from Sorangium cellulosum. Proc. Natl. Acad. Sci. USA 106 (2009) 16221–16226. [DOI] [PMID: 19805284]
5.  Holden, J.K., Lim, N. and Poulos, T.L. Identification of redox partners and development of a novel chimeric bacterial nitric oxide synthase for structure activity analyses. J. Biol. Chem. 289 (2014) 29437–29445. [DOI] [PMID: 25194416]
[EC 1.14.14.47 created 2012 as EC 1.14.13.165, transferred 2017 to EC 1.14.14.47]
 
 
EC 1.14.16.1     
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 phenylalanine and tyrosine biosynthesis, click here, of biopterin biosynthesis, click here and for mechanism of reaction, 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 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 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
References:
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. [DOI] [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. [DOI] [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. [DOI] [PMID: 12096915]
[EC 1.14.16.1 created 1961 as EC 1.99.1.2, transferred 1965 to EC 1.14.3.1, transferred 1972 to EC 1.14.16.1, modified 2002, modified 2003, modified 2019]
 
 
EC 1.14.16.2     
Accepted name: tyrosine 3-monooxygenase
Reaction: L-tyrosine + a 5,6,7,8-tetrahydropteridine + O2 = L-dopa + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
For diagram of dopa biosynthesis, click here and for diagram of biopterin biosynthesis, click here
Glossary: L-dopa = 3,4-dihydroxy-L-phenylalanine
Other name(s): L-tyrosine hydroxylase; tyrosine 3-hydroxylase; tyrosine hydroxylase
Systematic name: L-tyrosine,tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)
Comments: The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by EC 2.7.11.27, [acetyl-CoA carboxylase] kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 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: 9036-22-0
References:
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. [DOI] [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. [PMID: 14216443]
4.  Pigeon, D., Drissi-Daoudi, R., Gros, F. and Thibault, J. Copurification of tyrosine hydroxylase from rat pheochromocytoma by protein kinase. C. R. Acad. Sci. III 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]
[EC 1.14.16.2 created 1972, modified 2003, modified 2019]
 
 
EC 1.14.16.3      
Deleted entry: anthranilate 3-monooxygenase. Withdrawn owing to insufficient evidence.
[EC 1.14.16.3 created 1972, deleted 2020]
 
 
EC 1.14.16.4     
Accepted name: tryptophan 5-monooxygenase
Reaction: L-tryptophan + a 5,6,7,8-tetrahydropteridine + O2 = 5-hydroxy-L-tryptophan + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
For diagram of biopterin biosynthesis, click here
Other name(s): L-tryptophan hydroxylase; indoleacetic acid-5-hydroxylase; tryptophan 5-hydroxylase; tryptophan hydroxylase
Systematic name: L-tryptophan,tetrahydropteridine:oxygen oxidoreductase (5-hydroxylating)
Comments: The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 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: 9037-21-2
References:
1.  Friedman, P.A., Kappelman, A.H. and Kaufman, S. Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain. J. Biol. Chem. 247 (1972) 4165–4173. [PMID: 4402511]
2.  Hamon, M., Bourgoin, S., Artaud, F. and Glowinski, J. The role of intraneuronal 5-HT and of tryptophan hydroxylase activation in the control of 5-HT synthesis in rat brain slices incubated in K+-enriched medium. J. Neurochem. 33 (1979) 1031–1042. [DOI] [PMID: 315449]
3.  Ichiyama, A., Nakamura, S., Nishizuka, Y. and Hayaishi, O. Enzymic studies on the biosynthesis of serotonin in mammalian brain. J. Biol. Chem. 245 (1970) 1699–1709. [PMID: 5309585]
4.  Jequier, E., Robinson, B.S., Lovenberg, W. and Sjoerdsma, A. Further studies on tryptophan hydroxylase in rat brainstem and beef pineal. Biochem. Pharmacol. 18 (1969) 1071–1081. [DOI] [PMID: 5789774]
5.  Wang, L., Erlandsen, H., Haavik, J., Knappskog, P.M. and Stevens, R.C. Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin. Biochemistry 41 (2002) 12569–12574. [DOI] [PMID: 12379098]
[EC 1.14.16.4 created 1972, modified 2003, modified 2019]
 
 
EC 1.14.16.5     
Accepted name: alkylglycerol monooxygenase
Reaction: 1-O-alkyl-sn-glycerol + a 5,6,7,8-tetrahydropteridine + O2 = 1-O-(1-hydroxyalkyl)-sn-glycerol + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
Other name(s): glyceryl-ether monooxygenase; glyceryl-ether cleaving enzyme; glyceryl ether oxygenase; glyceryl etherase; O-alkylglycerol monooxygenase
Systematic name: 1-alkyl-sn-glycerol,tetrahydrobiopteridine:oxygen oxidoreductase
Comments: The enzyme cleaves alkylglycerols, but does not cleave alkenylglycerols (plasmalogens). Requires non-heme iron [7], reduced glutathione and phospholipids for full activity. The product spontaneously breaks down to form a fatty aldehyde and glycerol. The co-product, 4a-hydroxytetrahydropteridine, is rapidly dehydrated to 6,7-dihydropteridine, either spontaneously or by EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37256-82-9
References:
1.  Ishibashi, T. and Imai, Y. Solubilization and partial characterization of alkylglycerol monooxygenase from rat liver microsomes. Eur. J. Biochem. 132 (1983) 23–27. [DOI] [PMID: 6840084]
2.  Pfleger, E.C., Piantadosi, C. and Snyder, F. The biocleavage of isomeric glyceryl ethers by soluble liver enzymes in a variety of species. Biochim. Biophys. Acta 144 (1967) 633–648. [DOI] [PMID: 4383918]
3.  Snyder, F., Malone, B. and Piantadosi, C. Tetrahydropteridine-dependent cleavage enzyme for O-alkyl lipids: substrate specificity. Biochim. Biophys. Acta 316 (1973) 259–265. [DOI] [PMID: 4355017]
4.  Soodsma, J.F., Piantadosi, C. and Snyder, F. Partial characterization of the alkylglycerol cleavage enzyme system of rat liver. J. Biol. Chem. 247 (1972) 3923–3929. [PMID: 4402391]
5.  Tietz, A., Lindberg, M. and Kennedy, E.P. A new pteridine-requiring enzyme system for the oxidation of glyceryl ethers. J. Biol. Chem. 239 (1964) 4081–4090. [PMID: 14247652]
6.  Taguchi, H. and Armarego, W.L. Glyceryl-ether monooxygenase [EC 1.14.16.5]. A microsomal enzyme of ether lipid metabolism. Med. Res. Rev. 18 (1998) 43–89. [DOI] [PMID: 9436181]
7.  Watschinger, K., Keller, M.A., Hermetter, A., Golderer, G., Werner-Felmayer, G. and Werner, E.R. Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrobiopterin dependence. Biol. Chem. 390 (2009) 3–10. [DOI] [PMID: 19007315]
8.  Werner, E.R., Hermetter, A., Prast, H., Golderer, G. and Werner-Felmayer, G. Widespread occurrence of glyceryl ether monooxygenase activity in rat tissues detected by a novel assay. J. Lipid Res. 48 (2007) 1422–1427. [DOI] [PMID: 17303893]
[EC 1.14.16.5 created 1972 as EC 1.14.99.17, transferred 1976 to EC 1.14.16.5, modified 2010, modified 2020]
 
 
EC 1.14.16.6     
Accepted name: mandelate 4-monooxygenase
Reaction: (S)-2-hydroxy-2-phenylacetate + a 5,6,7,8-tetrahydropteridine + O2 = (S)-4-hydroxymandelate + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
Glossary: (S)-4-hydroxymandelate = (S)-2-hydroxy-2-(4-hydroxyphenyl)acetate
Other name(s): L-mandelate 4-hydroxylase; mandelic acid 4-hydroxylase
Systematic name: (S)-2-hydroxy-2-phenylacetate,tetrahydropteridine:oxygen oxidoreductase (4-hydroxylating)
Comments: Requires Fe2+. The enzyme has been characterized from the bacterium Pseudomonas putida. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 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, CAS registry number: 39459-82-0
References:
1.  Bhat, S.G. and Vaidyanathan, C.S. Purifications and properties of L-mandelate-4-hydroxylase from Pseudomonas convexa. Arch. Biochem. Biophys. 176 (1976) 314–323. [DOI] [PMID: 9909]
[EC 1.14.16.6 created 1984, modified 2020]
 
 
EC 1.14.16.7     
Accepted name: phenylalanine 3-monooxygenase
Reaction: L-phenylalanine + a 5,6,7,8-tetrahydropteridine + O2 = 3-hydroxy-L-phenylalanine + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
Glossary: 3-hydroxy-L-phenylalanine = meta-L-tyrosine = 3-(3-hydroxyphenyl)-L-alanine
Other name(s): PacX; phenylalanine 3-hydroxylase
Systematic name: L-phenylalanine,tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)
Comments: The enzyme, characterized from the bacterium Streptomyces coeruleorubidus, forms 3-hydroxy-L-phenylalanine (i.e. m-L-tyrosine), which is one of the building blocks in the biosynthesis of the uridyl peptide antibiotics pacidamycins. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 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
References:
1.  Zhang, W., Ames, B.D. and Walsh, C.T. Identification of phenylalanine 3-hydroxylase for meta-tyrosine biosynthesis. Biochemistry 50 (2011) 5401–5403. [DOI] [PMID: 21615132]
[EC 1.14.16.7 created 2014, modified 2019]
 
 
EC 3.5.4.16     
Accepted name: GTP cyclohydrolase I
Reaction: GTP + H2O = formate + 7,8-dihydroneopterin 3′-triphosphate
For diagram of the early stages of folate biosynthesis, click here
Glossary: 7,8-dihydroneopterin 3′-triphosphate = 6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterin
Other name(s): GTP cyclohydrolase; guanosine triphosphate cyclohydrolase; guanosine triphosphate 8-deformylase; dihydroneopterin triphosphate synthase; GTP 8-formylhydrolase
Systematic name: GTP 7,8-8,9-dihydrolase
Comments: The reaction involves hydrolysis of two C-N bonds and isomerization of the pentose unit; the recyclization may be non-enzymic. This enzyme is involved in the de novo synthesis of tetrahydrobiopterin from GTP, with the other enzymes involved being EC 1.1.1.153 (sepiapterin reductase) and EC 4.2.3.12 (6-pyruvoyltetrahydropterin synthase) [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37289-19-3
References:
1.  Burg, A.W. and Brown, G.M. The biosynthesis of folic acid. 8. Purification and properties of the enzyme that catalyzes the production of formate from carbon atom 8 of guanosine triphosphate. J. Biol. Chem. 243 (1968) 2349–2358. [PMID: 4296838]
2.  Wolf, W.A. and Brown, G.M. The biosynthesis of folic acid. X. Evidence for an Amadori rearrangement in the enzymatic formation of dihydroneopterin triphosphate from GTP. Biochim. Biophys. Acta 192 (1969) 468–478. [DOI] [PMID: 4904679]
3.  Supangat, S., Choi, Y.K., Park, Y.S., Son, D., Han, C.D. and Lee, K.H. Expression, purification, crystallization and preliminary X-ray analysis of sepiapterin reductase from Chlorobium tepidum. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 (2005) 202–204. [DOI] [PMID: 16510994]
[EC 3.5.4.16 created 1972]
 
 
EC 4.2.1.96     
Accepted name: 4a-hydroxytetrahydrobiopterin dehydratase
Reaction: 4a-hydroxytetrahydrobiopterin = 6,7-dihydrobiopterin + H2O
For diagram of biopterin biosynthesis, click here
Glossary: 4a-hydroxytetrahydrobiopterin = 6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-4a-hydroxypterin
6,7-dihydrobiopterin = 6-[(1R,2S)-1,2-dihydroxypropyl]-6,7-dihydropterin
Other name(s): 4α-hydroxy-tetrahydropterin dehydratase; 4a-carbinolamine dehydratase; pterin-4α-carbinolamine dehydratase; 4a-hydroxytetrahydrobiopterin hydro-lyase
Systematic name: 4a-hydroxytetrahydrobiopterin hydro-lyase (6,7-dihydrobiopterin-forming)
Comments: In concert with EC 1.5.1.34, 6,7-dihydropteridine reductase, the enzyme recycles 4a-hydroxytetrahydrobiopterin back to tetrahydrobiopterin, a cosubstrate for several enzymes, including aromatic amino acid hydroxylases. The enzyme is bifunctional, and also acts as a dimerization cofactor of hepatocyte nuclear factor-1α (HNF-1).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 87683-70-3
References:
1.  Citron, B.A., Davis, M.D., Milstien, S., Gutierrez, J., Mendel, D.B., Crabtree, G.R. and Kaufman, S. Identity of 4a-carbinolamine dehydratase, a component of the phenylalanine hydroxylation system, and DCoH, a transregulator of homeodomain proteins. Proc. Natl. Acad. Sci. USA 89 (1992) 11891–11894. [PMID: 1465414]
2.  Hauer, C.R., Rebrin, I., Thöny, B., Neuheiser, F., Curtius, H.C., Hunziker, P., Blau, N., Ghisla, S., Heizmann, C.W. Phenylalanine hydroxylase-stimulating protein: pterin-4α-carbinolamine dehydratase from rat and human liver. J. Biol. Chem. 268 (1993) 4828–4831. [PMID: 8444860]
3.  Thony, B., Neuheiser, F., Blau, N. and Heizmann, C.W. Characterization of the human PCBD gene encoding the bifunctional protein pterin-4 α-carbinolamine dehydratase/dimerization cofactor for the transcription factor HNF-1 α. Biochem. Biophys. Res. Commun. 210 (1995) 966–973. [PMID: 7763270]
4.  Endrizzi, J.A., Cronk, J.D., Wang, W., Crabtree, G.R. and Alber, T. Crystal structure of DCoH, a bifunctional, protein-binding transcriptional coactivator. Science 268 (1995) 556–559. [PMID: 7725101]
5.  Cronk, J.D., Endrizzi, J.A. and Alber, T. High-resolution structures of the bifunctional enzyme and transcriptional coactivator DCoH and its complex with a product analogue. Protein Sci. 5 (1996) 1963–1972. [PMID: 8897596]
[EC 4.2.1.96 created 1999, modified 2020]
 
 
EC 4.2.3.12     
Accepted name: 6-pyruvoyltetrahydropterin synthase
Reaction: 7,8-dihydroneopterin 3′-triphosphate = 6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
For diagram of biopterin biosynthesis, click here
Glossary: 7,8-dihydroneopterin 3′-triphosphate = 6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterin
Other name(s): 2-amino-4-oxo-6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydroxypteridine triphosphate lyase; 6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterin triphosphate-lyase (6-pyruvoyl-5,6,7,8-tetrahydropterin-forming)
Systematic name: 7,8-dihydroneopterin 3′-triphosphate triphosphate-lyase (6-pyruvoyl-5,6,7,8-tetrahydropterin-forming)
Comments: Catalyses triphosphate elimination and an intramolecular redox reaction in the presence of Mg2+. It has been identified in human liver. This enzyme is involved in the de novo synthesis of tetrahydrobiopterin from GTP, with the other enzymes involved being EC 1.1.1.153 (sepiapterin reductase) and EC 3.5.4.16 (GTP cyclohydrolase I) [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 97089-82-2
References:
1.  Milstien, S., Kaufman, S. The biosynthesis of tetrahydrobiopterin in rat brain. Purification and characterization of 6-pyruvoyl-tetrahydrobiopterin(2′-oxo) reductase. J. Biol. Chem. 264 (1989) 8066–8073. [PMID: 2656673]
2.  Thöny, B., Leimbacher, W., Bürgisser, D., Heinzmann, C.W. Human 6-pyruvoyl-tetrahydrobiopterin synthase: cDNA cloning and heterologous expression of the recombinant enzyme. Biochem. Biophys. Res. Commun. 189 (1992) 1437–1443. [DOI] [PMID: 1282802]
3.  Supangat, S., Choi, Y.K., Park, Y.S., Son, D., Han, C.D. and Lee, K.H. Expression, purification, crystallization and preliminary X-ray analysis of sepiapterin reductase from Chlorobium tepidum. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 (2005) 202–204. [DOI] [PMID: 16510994]
[EC 4.2.3.12 created 1999 as EC 4.6.1.10, transferred 2000 to EC 4.2.3.12, modified 2001]
 
 


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