The Enzyme Database

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EC 1.14.13.32     
Accepted name: albendazole monooxygenase
Reaction: albendazole + NADPH + H+ + O2 = albendazole S-oxide + NADP+ + H2O
For diagram of albendazole metabolism, click here
Glossary: albendazole = methyl [5-(propylsulfanyl)-1H-benzimidazol-2-yl]carbamate
Other name(s): albendazole oxidase (misleading); albendazole sulfoxidase (ambiguous); FMO3 (gene name); albendazole monooxygenase (flavin-containing)
Systematic name: albendazole,NADPH:oxygen oxidoreductase (sulfoxide-forming)
Comments: A microsomal flavin-containing monooxygenase. A similar conversion is also carried out by some microsomal cytochrome P-450 enzymes [EC 1.14.14.73, albendazole monooxygenase (sulfoxide-forming)]. It is estimated that cytochrome P-450s are responsible for 70% of the activity.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 101299-59-6
References:
1.  Fargetton, X., Galtier, P. and Delatour, P. Sulfoxidation of albendazole by a cytochrome P450-independent monooxygenase from rat liver microsomes. Vet. Res. Commun. 10 (1986) 317–324. [PMID: 3739217]
2.  Moroni, P., Buronfosse, T., Longin-Sauvageon, C., Delatour, P. and Benoit, E. Chiral sulfoxidation of albendazole by the flavin adenine dinucleotide-containing and cytochrome P450-dependent monooxygenases from rat liver microsomes. Drug Metab. Dispos. 23 (1995) 160–165. [PMID: 7736906]
3.  Rawden, H.C., Kokwaro, G.O., Ward, S.A. and Edwards, G. Relative contribution of cytochromes P-450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes. Br. J. Clin. Pharmacol. 49 (2000) 313–322. [PMID: 10759686]
[EC 1.14.13.32 created 1989, modified 2018]
 
 
EC 1.14.14.73     
Accepted name: albendazole monooxygenase (sulfoxide-forming)
Reaction: (1) albendazole + [reduced NADPH—hemoprotein reductase] + O2 = albendazole S-oxide + [oxidized NADPH—hemoprotein reductase] + H2O
(2) fenbendazole + [reduced NADPH—hemoprotein reductase] + O2 = fenbendazole S-oxide + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of albendazole metabolism, click here
Glossary: albendazole = methyl [5-(propylsulfanyl)-1H-benzimidazol-2-yl]carbamate
fenbendazole = methyl [5-(phenylsulfanyl)-1H-benzimidazol-2-yl]carbamate
Other name(s): albendazole sulfoxidase (ambiguous); albendazole hydroxylase (ambiguous); CYP3A4 (gene name); CYP2J2 (gene name); CYP1A2 (gene name)
Systematic name: albendazole,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (sulfoxide-forming)
Comments: This is one of the activities carried out by some microsomal cytochrome P-450 monooxygenases. A similar conversion is also carried out by a different microsomal enzyme (EC 1.14.13.32, albendazole monooxygenase (flavin-containing)), but it is estimated that cytochrome P-450s are responsible for 70% of the activity.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9059-22-7
References:
1.  Moroni, P., Buronfosse, T., Longin-Sauvageon, C., Delatour, P. and Benoit, E. Chiral sulfoxidation of albendazole by the flavin adenine dinucleotide-containing and cytochrome P450-dependent monooxygenases from rat liver microsomes. Drug Metab. Dispos. 23 (1995) 160–165. [PMID: 7736906]
2.  Rawden, H.C., Kokwaro, G.O., Ward, S.A. and Edwards, G. Relative contribution of cytochromes P-450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes. Br. J. Clin. Pharmacol. 49 (2000) 313–322. [PMID: 10759686]
3.  Asteinza, J., Camacho-Carranza, R., Reyes-Reyes, R.E., Dorado-Gonzalez, V., V. and Espinosa-Aguirre, J.J. Induction of cytochrome P450 enzymes by albendazole treatment in the rat. Environ Toxicol Pharmacol 9 (2000) 31–37. [PMID: 11137466]
4.  Lee, C.A., Neul, D., Clouser-Roche, A., Dalvie, D., Wester, M.R., Jiang, Y., Jones, J.P., 3rd, Freiwald, S., Zientek, M. and Totah, R.A. Identification of novel substrates for human cytochrome P450 2J2. Drug Metab. Dispos. 38 (2010) 347–356. [DOI] [PMID: 19923256]
5.  Wu, Z., Lee, D., Joo, J., Shin, J.H., Kang, W., Oh, S., Lee, D.Y., Lee, S.J., Yea, S.S., Lee, H.S., Lee, T. and Liu, K.H. CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems. Antimicrob. Agents Chemother. 57 (2013) 5448–5456. [DOI] [PMID: 23959307]
[EC 1.14.14.73 created 2018]
 
 
EC 1.14.14.74     
Accepted name: albendazole monooxygenase (hydroxylating)
Reaction: albendazole + [reduced NADPH—hemoprotein reductase] + O2 = hydroxyalbendazole + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of albendazole metabolism, click here
Glossary: albendazole = methyl [5-(propylsulfanyl)-1H-benzimidazol-2-yl]carbamate
hydroxyalbendazole = methyl [5-(3-hydroxypropylsulfanyl)-1H-benzimidazol-2-yl]carbamate
Other name(s): CYP2J2 (gene name)
Systematic name: albendazole,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (hydroxylating)
Comments: CYP2J2 is a microsomal cytochrome P-450 monooxygenase that catalyses the hydroxylation of the terminal carbon of the propylsulfanyl chain in albendazole, a broad-spectrum anthelmintic used against gastrointestinal nematodes and the larval stages of cestodes. cf. EC 1.14.14.73, albendazole monooxygenase (sulfoxide-forming).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Wu, Z., Lee, D., Joo, J., Shin, J.H., Kang, W., Oh, S., Lee, D.Y., Lee, S.J., Yea, S.S., Lee, H.S., Lee, T. and Liu, K.H. CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems. Antimicrob. Agents Chemother. 57 (2013) 5448–5456. [DOI] [PMID: 23959307]
[EC 1.14.14.74 created 2018]
 
 
EC 1.14.14.75     
Accepted name: fenbendazole monooxygenase (4′-hydroxylating)
Reaction: fenbendazole + [reduced NADPH—hemoprotein reductase] + O2 = 4′-hydroxyfenbendazole + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of albendazole metabolism, click here
Glossary: fenbendazole = methyl [5-(phenylsulfanyl)-1H-benzimidazol-2-yl]carbamate
4′-hydroxyfenbendazole = methyl [5-(4-hydroxyphenylsulfanyl)-1H-benzimidazol-2-yl]carbamate
albendazole = methyl [5-(propylsulfanyl)-1H-benzimidazol-2-yl]carbamate
Other name(s): CYP2C19 (gene name)
Systematic name: fenbendazole,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (4′-hydroxylating)
Comments: CYP2C19 is microsomal cytochrome P-450 monooxygenase that catalyses the hydroxylation of the benzene ring of fenbendazole, a broad-spectrum anthelmintic used against gastrointestinal nematodes and the larval stages of cestodes. This activity is also carried out by CYP2J2. cf. EC 1.14.14.74, albendazole monooxygenase (hydroxylating). CYP2C19 does not act on albendazole.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Wu, Z., Lee, D., Joo, J., Shin, J.H., Kang, W., Oh, S., Lee, D.Y., Lee, S.J., Yea, S.S., Lee, H.S., Lee, T. and Liu, K.H. CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems. Antimicrob. Agents Chemother. 57 (2013) 5448–5456. [DOI] [PMID: 23959307]
[EC 1.14.14.75 created 2018]
 
 
EC 2.1.1.316     
Accepted name: mitomycin 6-O-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + 6-demethylmitomycin A = S-adenosyl-L-homocysteine + mitomycin A
(2) S-adenosyl-L-methionine + 6-demethylmitomycin B = S-adenosyl-L-homocysteine + mitomycin B
Glossary: mitomycin A = [(1aS,8S,8aR,8bS)-5-methyl-6,8a-dimethoxy-4,7-dioxo-1,1a,2,4,7,8,8a,8b-octahydroazirino[2′,3′:3,4]pyrrolo[1,2-a]indol-8-yl]methyl carbamate
mitomycin B = [(1aS,8S,8aR,8bS)-8a-hydroxy-5-methyl-6-methoxy-4,7-dioxo-1,1a,2,4,7,8,8a,8b-octahydroazirino[2′,3′:3,4]pyrrolo[1,2-a]indol-8-yl]methyl carbamate
Other name(s): MmcR; mitomycin 7-O-methyltransferase (incorrect); S-adenosyl-L-methionine:7-demethylmitomycin-A 7-O-methyltransferase (incorrect)
Systematic name: S-adenosyl-L-methionine:6-demethylmitomycin-A 6-O-methyltransferase
Comments: The enzyme, characterized from the bacterium Streptomyces lavendulae, is involved in the biosynthesis of the quinone-containing antibiotics mitomycin A and mitomycin B.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Gruschow, S., Chang, L.C., Mao, Y. and Sherman, D.H. Hydroxyquinone O-methylation in mitomycin biosynthesis. J. Am. Chem. Soc. 129 (2007) 6470–6476. [DOI] [PMID: 17461583]
2.  Singh, S., Chang, A., Goff, R.D., Bingman, C.A., Gruschow, S., Sherman, D.H., Phillips, G.N., Jr. and Thorson, J.S. Structural characterization of the mitomycin 7-O-methyltransferase. Proteins 79 (2011) 2181–2188. [DOI] [PMID: 21538548]
[EC 2.1.1.316 created 2015]
 
 
EC 2.1.3.3     
Accepted name: ornithine carbamoyltransferase
Reaction: carbamoyl phosphate + L-ornithine = phosphate + L-citrulline
For diagram of the urea cycle and arginine biosynthesis, click here
Other name(s): citrulline phosphorylase; ornithine transcarbamylase; OTC; carbamylphosphate-ornithine transcarbamylase; L-ornithine carbamoyltransferase; L-ornithine carbamyltransferase; L-ornithine transcarbamylase; ornithine carbamyltransferase
Systematic name: carbamoyl-phosphate:L-ornithine carbamoyltransferase
Comments: The plant enzyme also catalyses the reactions of EC 2.1.3.6 putrescine carbamoyltransferase, EC 2.7.2.2 carbamate kinase and EC 3.5.3.12 agmatine deiminase, thus acting as putrescine synthase, converting agmatine [(4-aminobutyl)guanidine] and ornithine into putrescine and citrulline, respectively.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9001-69-8
References:
1.  Bishop, S.H. and Grisolia, S. Crystalline ornithine transcarbamylase. Biochim. Biophys. Acta 139 (1967) 344–348. [DOI] [PMID: 6034676]
2.  Marshall, M. and Cohen, P.P. Ornithine transcarbamylase from Streptococcus faecalis and bovine liver. I. Isolation and subunit structure. J. Biol. Chem. 247 (1972) 1641–1653. [PMID: 4622303]
3.  Marshall, M. and Cohen, P.P. Ornithine transcarbamylase from Streptococcus faecalis and bovine liver. II. Multiple binding sites for carbamyl-P and L-norvaline, correlation with steady state kinetics. J. Biol. Chem. 247 (1972) 1654–1668. [PMID: 4622304]
4.  Marshall, M. and Cohen, P.P. Ornithine transcarbamylase from Streptococcus faecalis and bovine liver. 3. Effects of chemical modifications of specific residues on ligand binding and enzymatic activity. J. Biol. Chem. 247 (1972) 1669–1682. [PMID: 4622305]
[EC 2.1.3.3 created 1961]
 
 
EC 2.1.3.6     
Accepted name: putrescine carbamoyltransferase
Reaction: carbamoyl phosphate + putrescine = phosphate + N-carbamoylputrescine
Glossary: putrescine = butane-1,4-diamine
Other name(s): PTCase; putrescine synthase; putrescine transcarbamylase
Systematic name: carbamoyl-phosphate:putrescine carbamoyltransferase
Comments: The plant enzyme also catalyses the reactions of EC 2.1.3.3 ornithine carbamoyltransferase, EC 2.7.2.2 carbamate kinase and EC 3.5.3.12 agmatine deiminase, thus acting as putrescine synthase, converting agmatine [(4-aminobutyl)guanidine] and ornithine into putrescine and citrulline, respectively.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9076-55-5
References:
1.  Roon, R.J. and Barker, H.A. Fermentation of agmatine in Streptococcus faecalis: occurrence of putrescine transcarbamoylase. J. Bacteriol. 109 (1972) 44–50. [PMID: 4621632]
2.  Srivenugopal, K.S. and Adiga, P.R. Enzymic conversion of agmatine to putrescine in Lathyrus sativus seedlings. Purification and properties of a multifunctional enzyme (putrescine synthase). J. Biol. Chem. 256 (1981) 9532–9541. [PMID: 6895223]
[EC 2.1.3.6 created 1976]
 
 
EC 2.7.2.2     
Accepted name: carbamate kinase
Reaction: ATP + NH3 + hydrogencarbonate = ADP + carbamoyl phosphate + H2O (overall reaction)
(1a) ATP + carbamate = ADP + carbamoyl phosphate
(1b) NH3 + hydrogencarbonate = carbamate + H2O (spontaneous)
For diagram of AMP catabolism, click here
Other name(s): CKase; carbamoyl phosphokinase; carbamyl phosphokinase
Systematic name: ATP:carbamate phosphotransferase
Comments: The enzyme catalyses the reversible conversion of carbamoyl phosphate and ADP to ATP and carbamate, which hydrolyses to ammonia and hydrogencarbonate. The physiological role of the enzyme is to generate ATP.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9026-69-1
References:
1.  Jones, M.E., Spector, L. and Lipmann, F. Carbamyl phosphate, the carbamyl donor in enzymatic citrulline synthesis. J. Am. Chem. Soc. 77 (1955) 819–820.
2.  Davis, R.H. Carbamyl phosphate synthesis in Neurospora crassa. I. Preliminary characterization of arginine-specific carbamyl phosphokinase. Biochim. Biophys. Acta 107 (1965) 44–53. [DOI] [PMID: 5857367]
3.  Glasziou, K.T. The metabolism of arginine in Serratia marcescens. II. Carbamyladenosine diphosphate phosphoferase. Aust. J. Biol. Sci. 9 (1956) 253–262.
4.  Bishop, S.H. and Grisolia, S. Crystalline carbamate kinase. Biochim. Biophys. Acta 118 (1966) 211–215. [PMID: 4959296]
5.  Srivenugopal, K.S. and Adiga, P.R. Enzymic conversion of agmatine to putrescine in Lathyrus sativus seedlings. Purification and properties of a multifunctional enzyme (putrescine synthase). J. Biol. Chem. 256 (1981) 9532–9541. [PMID: 6895223]
[EC 2.7.2.2 created 1961, modified 2018]
 
 
EC 3.5.1.54     
Accepted name: allophanate hydrolase
Reaction: urea-1-carboxylate + H2O = 2 CO2 + 2 NH3
Glossary: allophanate = urea-1-carboxylate
Other name(s): allophanate lyase; AtzF; TrzF
Systematic name: urea-1-carboxylate amidohydrolase
Comments: Along with EC 3.5.2.15 (cyanuric acid amidohydrolase) and EC 3.5.1.84 (biuret amidohydrolase), this enzyme forms part of the cyanuric-acid metabolism pathway, which degrades s-triazide herbicides, such as atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-1,3,5-triazine], in bacteria. The yeast enzyme (but not that from green algae) also catalyses the reaction of EC 6.3.4.6, urea carboxylase, thus bringing about the hydrolysis of urea to CO2 and NH3 in the presence of ATP and bicarbonate. The enzyme from Pseudomonas sp. strain ADP has a narrow substrate specificity, being unable to use the structurally analogous compounds urea, hydroxyurea or methylcarbamate as substrate [6].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, UM-BBD, CAS registry number: 9076-72-6
References:
1.  Maitz, G.S., Haas, E.M. and Castric, P.A. Purification and properties of the allophanate hydrolase from Chlamydomonas reinhardii. Biochim. Biophys. Acta 714 (1982) 486–491.
2.  Roon, R.J. and Levenberg, B. Urea amidolyase. I. Properties of the enzyme from Candida utilis. J. Biol. Chem. 247 (1972) 4107–4113. [PMID: 4556303]
3.  Sumrada, R.A. and Cooper, T.G. Urea carboxylase and allophanate hydrolase are components of a multifunctional protein in yeast. J. Biol. Chem. 257 (1982) 9119–9127. [PMID: 6124544]
4.  Kanamori, T., Kanou, N., Kusakabe, S., Atomi, H. and Imanaka, T. Allophanate hydrolase of Oleomonas sagaranensis involved in an ATP-dependent degradation pathway specific to urea. FEMS Microbiol. Lett. 245 (2005) 61–65. [DOI] [PMID: 15796980]
5.  Cheng, G., Shapir, N., Sadowsky, M.J. and Wackett, L.P. Allophanate hydrolase, not urease, functions in bacterial cyanuric acid metabolism. Appl. Environ. Microbiol. 71 (2005) 4437–4445. [DOI] [PMID: 16085834]
6.  Shapir, N., Sadowsky, M.J. and Wackett, L.P. Purification and characterization of allophanate hydrolase (AtzF) from Pseudomonas sp. strain ADP. J. Bacteriol. 187 (2005) 3731–3738. [DOI] [PMID: 15901697]
7.  Shapir, N., Cheng, G., Sadowsky, M.J. and Wackett, L.P. Purification and characterization of TrzF: biuret hydrolysis by allophanate hydrolase supports growth. Appl. Environ. Microbiol. 72 (2006) 2491–2495. [DOI] [PMID: 16597948]
[EC 3.5.1.54 created 1986, modified 2008]
 
 
EC 3.5.1.110     
Accepted name: peroxyureidoacrylate/ureidoacrylate amidohydrolase
Reaction: (1) (Z)-3-ureidoacrylate peracid + H2O = (Z)-3-peroxyaminoacrylate + CO2 + NH3 (overall reaction)
(1a) (Z)-3-ureidoacrylate peracid + H2O = (Z)-3-peroxyaminoacrylate + carbamate
(1b) carbamate = CO2 + NH3 (spontaneous)
(2) (Z)-2-methylureidoacrylate peracid + H2O = (Z)-2-methylperoxyaminoacrylate + CO2 + NH3 (overall reaction)
(2a) (Z)-2-methylureidoacrylate peracid + H2O = (Z)-2-methylperoxyaminoacrylate + carbamate
(2b) carbamate = CO2 + NH3 (spontaneous)
Glossary: ureidoperacrylic acid = (Z)-3-ureidoacrylate peracid = (2Z)-3-(carbamoylamino)prop-2-eneperoxoic acid
(Z)-2-methylureidoperacrylic acid = (Z)-2-methylureidoacrylate peracid = (2Z)-3-(carbamoylamino)-2-methylprop-2-eneperoxoic acid
Other name(s): RutB
Systematic name: (Z)-3-ureidoacrylate peracid amidohydrolase
Comments: The enzyme also shows activity towards ureidoacrylate. Part of the Rut pyrimidine catabolic pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Kim, K.S., Pelton, J.G., Inwood, W.B., Andersen, U., Kustu, S. and Wemmer, D.E. The Rut pathway for pyrimidine degradation: novel chemistry and toxicity problems. J. Bacteriol. 192 (2010) 4089–4102. [DOI] [PMID: 20400551]
[EC 3.5.1.110 created 2012]
 
 
EC 3.5.2.15     
Accepted name: cyanuric acid amidohydrolase
Reaction: cyanuric acid + H2O = 1-carboxybiuret
Glossary: cyanuric acid = 1,3,5-triazine-2,4,6(1H,3H,5H)-trione = 2,4,6-trihydroxy-s-triazine
1-carboxybiuret = N-[(carbamoylamino)carbonyl]carbamate
Other name(s): atzD (gene name); trzD (gene name)
Systematic name: cyanuric acid amidohydrolase
Comments: The enzyme catalyses the ring cleavage of cyanuric acid, an intermediate in the degradation of s-triazide herbicides such as atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-1,3,5-triazine]. The enzyme is highly specific for cyanuric acid. The product was initially thought to be bioret, but was later shown to be 1-carboxybioret.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, UM-BBD, CAS registry number: 132965-78-7
References:
1.  Eaton, R.W. and Karns, J.S. Cloning and comparison of the DNA encoding ammelide aminohydrolase and cyanuric acid amidohydrolase from three s-triazine-degrading bacterial strains. J. Bacteriol. 173 (1991) 1363–1366. [DOI] [PMID: 1991731]
2.  Eaton, R.W. and Karns, J.S. Cloning and analysis of s-triazine catabolic genes from Pseudomonas sp. strain NRRLB-12227. J. Bacteriol. 173 (1991) 1215–1222. [DOI] [PMID: 1846859]
3.  Karns, J.S. Gene sequence and properties of an s-triazine ring-cleavage enzyme from Pseudomonas sp. strain NRRLB-12227. Appl. Environ. Microbiol. 65 (1999) 3512–3517. [PMID: 10427042]
4.  Fruchey, I., Shapir, N., Sadowsky, M.J. and Wackett, L.P. On the origins of cyanuric acid hydrolase: purification, substrates, and prevalence of AtzD from Pseudomonas sp. strain ADP. Appl. Environ. Microbiol. 69 (2003) 3653–3657. [DOI] [PMID: 12788776]
5.  Esquirol, L., Peat, T.S., Wilding, M., Liu, J.W., French, N.G., Hartley, C.J., Onagi, H., Nebl, T., Easton, C.J., Newman, J. and Scott, C. An unexpected vestigial protein complex reveals the evolutionary origins of an s-triazine catabolic enzyme. J. Biol. Chem. 293 (2018) 7880–7891. [PMID: 29523689]
[EC 3.5.2.15 created 2000, modified 2008, modified 2019]
 
 
EC 3.5.3.12     
Accepted name: agmatine deiminase
Reaction: agmatine + H2O = N-carbamoylputrescine + NH3
Glossary: agmatine = (4-aminobutyl)guanidine
Other name(s): agmatine amidinohydrolase
Systematic name: agmatine iminohydrolase
Comments: The plant enzyme also catalyses the reactions of EC 2.1.3.3 (ornithine carbamoyltransferase), EC 2.1.3.6 (putrescine carbamoyltransferase) and EC 2.7.2.2 (carbamate kinase), thus functioning as a putrescine synthase, converting agmatine and ornithine into putrescine and citrulline, respectively.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37289-17-1
References:
1.  Smith, T.A. Agmatine iminohydrolase in maize. Phytochemistry 8 (1969) 2111–2117.
2.  Srivenugopal, K.S. and Adiga, P.R. Enzymic conversion of agmatine to putrescine in Lathyrus sativus seedlings. Purification and properties of a multifunctional enzyme (putrescine synthase). J. Biol. Chem. 256 (1981) 9532–9541. [PMID: 6895223]
[EC 3.5.3.12 created 1972]
 
 
EC 4.2.1.104     
Accepted name: cyanase
Reaction: cyanate + HCO3- + 2 H+ = NH3 + 2 CO2 (overall reaction)
(1a) cyanate + HCO3- + H+ = carbamate + CO2
(1b) carbamate + H+ = NH3 + CO2 (spontaneous)
For diagram of reaction, click here
Glossary: cyanate = NCO-
carbamate = H2N-CO-O-
Other name(s): cyanate lyase; cyanate hydrolase; cyanate aminohydrolase; cyanate C-N-lyase; cyanate hydratase
Systematic name: carbamate hydro-lyase
Comments: This enzyme, which is found in bacteria and plants, is used to decompose cyanate, which can be used as the sole source of nitrogen [6,7]. Reaction (1) can be considered as the reverse of ’carbamate = cyanate + H2O′, where this is assisted by reaction with bicarbonate and carbon dioxide (see mechanism above) [2], and hence is classified in sub-subclass 4.2.1. Bicarbonate functions as a recycling substrate [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, UM-BBD, CAS registry number: 37289-24-0
References:
1.  Anderson, P.M. Purification and properties of the inducible enzyme cyanase. Biochemistry 19 (1980) 2882–2888. [PMID: 6994799]
2.  Johnson, W.V. and Anderson, P.M. Bicarbonate is a recycling substrate for cyanase. J. Biol. Chem. 262 (1987) 9021–9025. [PMID: 3110153]
3.  Taussig, A. The synthesis of the induced enzyme, "cyanase", in E. coli. Biochim. Biophys. Acta 44 (1960) 510–519. [PMID: 13775509]
4.  Taussig, A. Some properties of the induced enzyme cyanase. Can. J. Biochem. 43 (1965) 1063–1069. [PMID: 5322950]
5.  Anderson, P.M., Korte, J.J. and Holcomb, T.A. Reaction of the N-terminal methionine residues in cyanase with diethylpyrocarbonate. Biochemistry 33 (1994) 14121–14125. [PMID: 7947823]
6.  Kozliak, E.I., Fuchs, J.A., Guilloton, M.B. and Anderson, P.M. Role of bicarbonate/CO2 in the inhibition of Escherichia coli growth by cyanate. J. Bacteriol. 177 (1995) 3213–3219. [DOI] [PMID: 7768821]
7.  Walsh, M.A., Otwinowski, Z., Perrakis, A., Anderson, P.M. and Joachimiak, A. Structure of cyanase reveals that a novel dimeric and decameric arrangement of subunits is required for formation of the enzyme active site. Structure 8 (2000) 505–514. [DOI] [PMID: 10801492]
[EC 4.2.1.104 created 1972 as EC 3.5.5.3, transferred 1990 to EC 4.3.99.1, transferred 2001 to EC 4.2.1.104, modified 2007]
 
 
EC 6.3.4.16     
Accepted name: carbamoyl-phosphate synthase (ammonia)
Reaction: 2 ATP + NH3 + hydrogencarbonate = 2 ADP + phosphate + carbamoyl phosphate (overall reaction)
(1a) ATP + hydrogencarbonate = ADP + carboxyphosphate
(1b) NH3 + carboxyphosphate = carbamate + phosphate
(1c) ATP + carbamate = ADP + carbamoyl phosphate
For diagram of pyrimidine biosynthesis, click here
Other name(s): carbon-dioxide—ammonia ligase; carbamoylphosphate synthase; carbamylphosphate synthetase; carbamoylphosphate synthase (ammonia); carbamoylphosphate synthetase; carbamylphosphate synthetase I; CPSI (gene name); carbon-dioxide:ammonia ligase (ADP-forming, carbamate-phosphorylating)
Systematic name: hydrogencarbonate:ammonia ligase (ADP-forming, carbamate-phosphorylating)
Comments: The enzyme catalyses the first committed step in the urea cycle. The reaction proceeds via three separate chemical reactions: phosphorylation of hydrogencarbonate to carboxyphosphate; a nucleophilic attack of ammonia on carboxyphosphate yielding carbamate; and the phosphorylation of carbamate forming carbamoyl phosphate. Two moles of ATP are utilized for the synthesis of one molecule of carbamyl phosphate, making the reaction essentially irreversible. The enzyme requires the allosteric activator N-acetyl-L-glutamate. cf. EC 6.3.5.5, carbamoyl-phosphate synthase (glutamine-hydrolysing).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9026-23-7
References:
1.  Fahien, L.A. and Cohen, P.P. A kinetic study of carbamyl phosphate synthetase. J. Biol. Chem. 239 (1964) 1925–1934. [PMID: 14213379]
2.  Jones, M.E. and Spector, L. The pathway of carbonate in the biosynthesis of carbamyl phosphate. J. Biol. Chem. 235 (1960) 2897–2901. [PMID: 13790558]
3.  Marshall, M., Metzenberg, R.L. and Cohen, P.P. Purification of carbamyl phosphate synthetase from frog liver. J. Biol. Chem. 233 (1958) 102–105. [PMID: 13563449]
4.  Marshall, M., Metzenberg, R.L. and Cohen, P.P. Physical and kinetic properties of carbamyl phosphate synthetase from frog liver. J. Biol. Chem. 236 (1961) 2229–2237. [PMID: 26151989]
5.  Pierson, D.L. and Brien, J.M. Human carbamylphosphate synthetase I. Stabilization, purification, and partial characterization of the enzyme from human liver. J. Biol. Chem. 255 (1980) 7891–7895. [PMID: 6249820]
6.  Pekkala, S., Martinez, A.I., Barcelona, B., Gallego, J., Bendala, E., Yefimenko, I., Rubio, V. and Cervera, J. Structural insight on the control of urea synthesis: identification of the binding site for N-acetyl-L-glutamate, the essential allosteric activator of mitochondrial carbamoyl phosphate synthetase. Biochem. J. 424 (2009) 211–220. [DOI] [PMID: 19754428]
[EC 6.3.4.16 created 1965 as EC 2.7.2.5, transferred 1978 to EC 6.3.4.16]
 
 
EC 6.3.5.5     
Accepted name: carbamoyl-phosphate synthase (glutamine-hydrolysing)
Reaction: 2 ATP + L-glutamine + hydrogencarbonate + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + hydrogencarbonate = ADP + carboxyphosphate
(1c) NH3 + carboxyphosphate = carbamate + phosphate
(1d) ATP + carbamate = ADP + carbamoyl phosphate
For diagram of pyrimidine biosynthesis, click here
Other name(s): carbamoyl-phosphate synthetase (glutamine-hydrolysing); carbamyl phosphate synthetase (glutamine); carbamoylphosphate synthetase II; glutamine-dependent carbamyl phosphate synthetase; carbamoyl phosphate synthetase; CPS; carbon-dioxide:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating); carA (gene name); carB (gene name); CAD (gene name); hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)
Systematic name: hydrogencarbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)
Comments: The product carbamoyl phosphate is an intermediate in the biosynthesis of arginine and the pyrimidine nucleotides [4]. The enzyme from Escherichia coli has three separate active sites, which are connected by a molecular tunnel that is almost 100 Å in length [8]. The amidotransferase domain within the small subunit of the enzyme hydrolyses glutamine to ammonia via a thioester intermediate. The ammonia migrates through the interior of the protein, where it reacts with carboxyphosphate to produce the carbamate intermediate. The carboxyphosphate intermediate is formed by the phosphorylation of hydrogencarbonate by ATP at a site contained within the N-terminal half of the large subunit. The carbamate intermediate is transported through the interior of the protein to a second site within the C-terminal half of the large subunit, where it is phosphorylated by another ATP to yield the final product, carbamoyl phosphate [6]. cf. EC 6.3.4.16, carbamoyl-phosphate synthase (ammonia).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37233-48-0
References:
1.  Anderson, P.M. and Meister, A. Evidence for an activated form of carbon dioxide in the reaction catalysed by Escherichia coli carbamyl phosphate synthetase. Biochemistry 4 (1965) 2803–2809. [PMID: 5326356]
2.  Kalman, S.M., Duffield, P.H. and Brzozowski, T. Purification and properties of a bacterial carbamyl phosphate synthetase. J. Biol. Chem. 241 (1966) 1871–1877. [PMID: 5329589]
3.  Yip, M.C.M. and Knox, W.E. Glutamine-dependent carbamyl phosphate synthetase. Properties and distribution in normal and neoplastic rat tissues. J. Biol. Chem. 245 (1970) 2199–2204. [PMID: 5442268]
4.  Stapleton, M.A., Javid-Majd, F., Harmon, M.F., Hanks, B.A., Grahmann, J.L., Mullins, L.S. and Raushel, F.M. Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase. Biochemistry 35 (1996) 14352–14361. [DOI] [PMID: 8916922]
5.  Holden, H.M., Thoden, J.B. and Raushel, F.M. Carbamoyl phosphate synthetase: a tunnel runs through it. Curr. Opin. Struct. Biol. 8 (1998) 679–685. [DOI] [PMID: 9914247]
6.  Raushel, F.M., Thoden, J.B., Reinhart, G.D. and Holden, H.M. Carbamoyl phosphate synthetase: a crooked path from substrates to products. Curr. Opin. Chem. Biol. 2 (1998) 624–632. [DOI] [PMID: 9818189]
7.  Raushel, F.M., Thoden, J.B. and Holden, H.M. The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia. Biochemistry 38 (1999) 7891–7899. [DOI] [PMID: 10387030]
8.  Thoden, J.B., Huang, X., Raushel, F.M. and Holden, H.M. Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia. J. Biol. Chem. 277 (2002) 39722–39727. [DOI] [PMID: 12130656]
[EC 6.3.5.5 created 1972 as EC 2.7.2.9, transferred 1978 to EC 6.3.5.5, modified 2006]
 
 


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