Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB)

Proposed Changes to the Enzyme List

The entries below are additions and amendments to the Enzyme Nomenclature list. They were prepared for the NC-IUBMB by Keith Tipton, Sinéad Boyce, Gerry Moss and Hal Dixon, with occasional help from other Committee members, and were put on the web by Gerry Moss. Comments and suggestions on these entries should be sent to Professor K.F. Tipton and Dr S. Boyce (Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland). The entries were added on the date indicated and fully approved after a month.

An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.


Contents

EC 1.1.1.291 2-hydroxymethylglutarate dehydrogenase (11 December 2006)
*EC 1.1.3.8 L-gulonolactone oxidase (17 November 2006)
EC 1.1.3.24 now EC 1.3.3.12 (17 November 2006)
EC 1.1.99.31 (S)-mandelate dehydrogenase (11 December 2006)
*EC 1.3.2.3 L-galactonolactone dehydrogenase (17 November 2006)
EC 1.3.3.12 L-galactonolactone oxidase (17 November 2006)
EC 1.4.3.20 L-lysine 6-oxidase (25 October 2006)
*EC 1.7.3.1 nitroalkane oxidase (11 December 2006)
*EC 1.13.11.32 2-nitropropane dioxygenase (until 11 December 2006)
*EC 2.1.1.69 5-hydroxyfuranocoumarin 5-O-methyltransferase (25 October 2006)
*EC 2.1.1.70 8-hydroxyfuranocoumarin 8-O-methyltransferase (25 October 2006)
EC 2.1.1.92 deleted, now EC 2.1.1.69 (25 October 2006)
EC 2.7.7.64 UTP-monosaccharide-1-phosphate uridylyltransferase (11 December 2006)
EC 2.7.8.27 sphingomyelin synthase (until 11 December 2006)
EC 3.4.13.22 D-Ala-D-Ala dipeptidase (17 November 2006)
EC 3.5.2.18 enamidase (11 December 2006)
EC 4.2.1.110 aldos-2-ulose dehydratase (until 11 December 2006)
EC 4.2.1.111 1,5-anhydro-D-fructose dehydratase (11 December 2006)
EC 5.3.3.15 ascopyrone tautomerase (11 December 2006)
EC 6.3.1.12 D-aspartate ligase (11 December 2006)
EC 6.4.1.7 2-oxoglutarate carboxylase (11 December 2006)

EC 1.1.1.291

Accepted name: 2-hydroxymethylglutarate dehydrogenase

Reaction: (S)-2-hydroxymethylglutarate + NAD+ = 2-formylglutarate + NADH + H+

For diagram click here.

Other name(s): HgD

Systematic name: (S)-2-hydroxymethylglutarate:NAD+ oxidoreductase

Comments: NADP+ cannot replace NAD+. Forms part of the nicotinate-fermentation catabolism pathway in Eubacterium barkeri. Other enzymes involved in this pathway are EC 1.17.1.5 (nicotinate dehydrogenase), EC 1.3.7.1 (6-hydroxynicotinate reductase), EC 3.5.2.18 (enamidase), EC 5.4.99.4 (2-methyleneglutarate mutase), EC 5.3.3.6 (methylitaconate Δ-isomerase), EC 4.2.1.85 (dimethylmaleate hydratase) and EC 4.1.3.32 (2,3-dimethylmalate lyase).

References:

1. Alhapel, A., Darley, D.J., Wagener, N., Eckel, E., Elsner, N. and Pierik, A.J. Molecular and functional analysis of nicotinate catabolism in Eubacterium barkeri. Proc. Natl. Acad. Sci. USA 103 (2006) 12341-12346. [PMID: 16894175]

[EC 1.1.1.291 created 2006]

*EC 1.1.3.8

Accepted name: L-gulonolactone oxidase

Reaction: (1) L-gulono-1,4-lactone + O2 = L-xylo-hex-2-ulono-1,4-lactone + H2O2
(2) L-xylo-hex-2-ulono-1,4-lactone = L-ascorbate (spontaneous)

For diagram click here.

Other name(s): L-gulono-γ-lactone: O2 oxidoreductase; L-gulono-γ-lactone oxidase; L-gulono-γ-lactone:oxidoreductase; GLO

Systematic name: L-gulono-1,4-lactone:oxygen 3-oxidoreductase

Comments: A microsomal flavoprotein (FAD). The product spontaneously isomerizes to L-ascorbate. While most higher animals can synthesize asborbic acid, primates and guinea pigs cannot [3].

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 9028-78-8

References:

1. Isherwood, F.A., Mapson, L.W. and Chen, Y.T. Synthesis of L-ascorbic acid in rat liver homogenates. Conversion of L-gulono- and L-galactono-γ-lactone and the respective acids into L-ascorbic acid. Biochem. J. 76 (1960) 157-171. [PMID: 14405898]

2. Kiuchi, K., Noshikimi, M. and Yagi, K. Purification and characterization of L-gulonolactone oxidase from chicken kidney microsomes. Biochemistry 21 (1982) 5076-5082. [PMID: 7138847]

3. Nishikimi, M., Fukuyama, R., Minoshima, S., Shimizu, N. and Yagi, K. Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-γ-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J. Biol. Chem. 269 (1994) 13685-13688. [PMID: 8175804]

4. Chatterjee, I.B., Chatterjee, G.C., Ghosh, N.C. and Guha, B.C. Identification of 2-keto-L-gulonolactone as an intermediate in the biosynthesis of L-ascorbic acid. Naturwissenschaften 46 (1959) 475 only.

[EC 1.1.3.8 created 1965, modified 2001, modified 2006]

EC 1.1.99.31

Accepted name: (S)-mandelate dehydrogenase

Reaction: (S)-2-hydroxy-2-phenylacetate + acceptor = 2-oxo-2-phenylacetate + reduced acceptor

For diagram click here.

Glossary: (S)-mandelate = (S)-2-hydroxy-2-phenylacetate
2-oxo-2-phenylacetate = benzoylformate

Other name(s): MDH

Systematic name: (S)-2-hydroxy-2-phenylacetate:acceptor 2-oxidoreductase

Comments: This enzyme is a member of the FMN-dependent α-hydroxy-acid oxidase/dehydrogenase family [1]. While all enzymes of this family oxidize the (S)-enantiomer of an α-hydroxy acid to an α-oxo acid, the ultimate oxidant (oxygen, intramolecular heme or some other acceptor) depends on the particular enzyme. This enzyme transfers the electron pair from FMNH2 to a component of the electron transport chain, most probably ubiquinone [1,2]. It is part of a metabolic pathway in Pseudomonads that allows these organisms to utilize mandelic acid, derivatized from the common soil metabolite amygdalin, as the sole source of carbon and energy [2]. The enzyme has a large active-site pocket and preferentially binds substrates with longer sidechains, e.g. 2-hydroxyoctanoate rather than 2-hydroxybutyrate [1]. It also prefers substrates that, like (S)-mandelate, have β unsaturation, e.g. (indol-3-yl)glycolate compared with (indol-3-yl)lactate [1]. Esters of mandelate, such as methyl (S)-mandelate, are also substrates [3].

References:

1. Lehoux, I.E. and Mitra, B. (S)-Mandelate dehydrogenase from Pseudomonas putida: mechanistic studies with alternate substrates and pH and kinetic isotope effects. Biochemistry 38 (1999) 5836-5848. [PMID: 10231535]

2. Dewanti, A.R., Xu, Y. and Mitra, B. Role of glycine 81 in (S)-mandelate dehydrogenase from Pseudomonas putida in substrate specificity and oxidase activity. Biochemistry 43 (2004) 10692-10700. [PMID: 15311930]

3. Dewanti, A.R., Xu, Y. and Mitra, B. Esters of mandelic acid as substrates for (S)-mandelate dehydrogenase from Pseudomonas putida: implications for the reaction mechanism. Biochemistry 43 (2004) 1883-1890. [PMID: 14967029]

[EC 1.1.99.31 created 2006]

[EC 1.1.3.24 Transferred entry: L-galactonolactone oxidase. Now EC 1.3.3.12, L-galactonolactone oxidase. The enzyme had been incorrectly classified as acting upon a CH-OH donor rather than a CH-CH donor. (EC 1.1.3.24 created 1984, deleted 2006)]

*EC 1.3.2.3

Accepted name: L-galactonolactone dehydrogenase

Reaction: (1) L-galactono-1,4-lactone + 2 ferricytochrome c = L-ascorbate + 2 ferrocytochrome c
(2) L-ascorbate + 2 ferricytochrome c = L-dehydroascorbate + 2 ferrocytochrome c (spontaneous)

Other name(s): galactonolactone dehydrogenase; L-galactono-γ-lactone dehydrogenase; L-galactono-γ-lactone:ferricytochrome-c oxidoreductase; GLDHase; GLDase

Systematic name: L-galactono-1,4-lactone:ferricytochrome-c oxidoreductase

Comments: This enzyme catalyses the final step in the biosynthesis of L-ascorbic acid in higher plants and in nearly all higher animals with the exception of primates and some birds [5]. The enzyme is very specific for its substrate L-galactono-1,4-lactone as D-galactono-γ-lactone, D-gulono-γ-lactone, L-gulono-γ-lactone, D-erythronic-γ-lactone, D-xylonic-γ-lactone, L-mannono-γ-lactone, D-galactonate, D-glucuronate and D-gluconate are not substrates [5]. FAD, NAD+, NADP+ and O2 (cf. EC 1.3.3.12, L-galactonolactone oxidase) cannot act as electron acceptor [5].

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 9029-02-1

References:

1. Mapson, L.W. and Breslow, E. Properties of partially purified L-galactono-γ-lactone dehydrogenase. Biochem. J. 65 (1957) 29 only.

2. Mapson, L.W., Isherwood, F.A. and Chen, Y.T. Biological synthesis of L-ascorbic acid: the conversion of L-galactono-γ-lactone into L-ascorbic acid by plant mitochondria. Biochem. J. 56 (1954) 21-28. [PMID: 13126087]

3. Isherwood, F.A., Chen, Y.T. and Mapson, L.W. Synthesis of L-ascorbic acid in plants and animals. Biochem. J. 56 (1954) 1-15. [PMID: 13126085]

4. Ôba, K., Ishikawa, S., Nishikawa, M., Mizuno, H. and Yamamoto, T. Purification and properties of L-galactono-γ-lactone dehydrogenase, a key enzyme for ascorbic acid biosynthesis, from sweet potato roots. J. Biochem. (Tokyo) 117 (1995) 120-124. [PMID: 7775377]

5. Østergaard, J., Persiau, G., Davey, M.W., Bauw, G. and Van Montagu, M. Isolation of a cDNA coding for L-galactono-γ-lactone dehydrogenase, an enzyme involved in the biosynthesis of ascorbic acid in plants. Purification, characterization, cDNA cloning, and expression in yeast. J. Biol. Chem. 272 (1997) 30009-30016. [PMID: 9374475]

[EC 1.3.2.3 created 1961, modified 2006]

EC 1.3.3.12

Accepted name: L-galactonolactone oxidase

Reaction: L-galactono-1,4-lactone + O2 = L-ascorbate + H2O2

Other name(s): L-galactono-1,4-lactone oxidase

Systematic name: L-galactono-1,4-lactone:oxygen 3-oxidoreductase

Comments: A flavoprotein. Acts on the 1,4-lactones of L-galactonic, D-altronic, L-fuconic, D-arabinic and D-threonic acids; not identical with EC 1.1.3.8 L-gulonolactone oxidase. (cf. EC 1.3.2.3 galactonolactone dehydrogenase).

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:

References:

1. Bleeg, H.S. and Christensen, F. Biosynthesis of ascorbate in yeast. Purification of L-galactono-1,4-lactone oxidase with properties different from mammalian L-gulonolactone oxidase. Eur. J. Biochem. 127 (1982) 391-396. [PMID: 6754380]

[EC 1.3.3.12 created 1984 as EC 1.1.3.24, transferred 2006 to EC 1.3.3.12]

EC 1.4.3.20

Accepted name: L-lysine 6-oxidase

Reaction: L-lysine + O2 + H2O = 2-aminoadipate 6-semialdehyde + H2O2 + NH3

Glossary: 2-aminoadipate 6-semialdehyde = allysine = (S)-2-amino-6-oxohexanoate

Other name(s): L-lysine-ε-oxidase; Lod; LodA; marinocine

Systematic name: L-lysine:oxygen 6-oxidoreductase (deaminating)

Comments: Differs from EC 1.4.3.13, protein-lysine 6-oxidase, by using free L-lysine rather than the protein-bound form. 2-N-Acetyl-L-lysine is also a substrate, but 6-N-acetyl-L-lysine, which has an acetyl group at position 6, is not a substrate. Also acts on L-ornithine, D-lysine and 4-hydroxy-L-lysine, but more slowly. The amines cadaverine and putrescine are not substrates [2].

References:

1. Lucas-Elío, P., Gómez, D., Solano, F. and Sanchez-Amat, A. The antimicrobial activity of marinocine, synthesized by Marinomonas mediterranea, is due to hydrogen peroxide generated by its lysine oxidase activity. J. Bacteriol. 188 (2006) 2493-2501. [PMID: 16547036]

2. Gómez, D., Lucas-Elío, P., Sanchez-Amat, A. and Solano, F. A novel type of lysine oxidase: L-lysine-ε-oxidase. Biochim. Biophys. Acta 1764 (2006) 1577-1585. [PMID: 17030025]

[EC 1.4.3.20 created 2006]

*EC 1.7.3.1

Accepted name: nitroalkane oxidase

Reaction: a nitroalkane + H2O + O2 = an aldehyde or ketone + nitrite + H2O2

Other name(s): nitroethane oxidase; NAO; nitroethane:oxygen oxidoreductase

Systematic name: nitroalkane:oxygen oxidoreductase

Comments: Has an absolute requirement for FAD [4]. While nitroethane may be the physiological substrate [2], the enzyme also acts on several other nitroalkanes, including 1-nitropropane, 2-nitropropane, 1-nitrobutane, 1-nitropentane, 1-nitrohexane, nitrocyclohexane and some nitroalkanols [4]. Differs from EC 1.13.11.32, 2-nitropropane dioxygenase, in that the preferred substrates are neutral nitroalkanes rather than anionic nitronates [4].

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 9029-36-1

References:

1. Little, H.N. Oxidation of nitroethane by extracts from Neurospora. J. Biol. Chem. 193 (1951) 347-358. [PMID: 14907722]

2. Kido, T., Hashizume, K. and Soda, K. Purification and properties of nitroalkane oxidase from Fusarium oxysporum. J. Bacteriol. 133 (1978) 53-58. [PMID: 22538]

3. Daubner, S.C., Gadda, G., Valley, M.P. and Fitzpatrick, P.F. Cloning of nitroalkane oxidase from Fusarium oxysporum identifies a new member of the acyl-CoA dehydrogenase superfamily. Proc. Natl. Acad. Sci. USA 99 (2002) 2702-2707. [PMID: 11867731]

4. Fitzpatrick, P.F., Orville, A.M., Nagpal, A. and Valley, M.P. Nitroalkane oxidase, a carbanion-forming flavoprotein homologous to acyl-CoA dehydrogenase. Arch. Biochem. Biophys. 433 (2005) 157-165. [PMID: 15581574]

5. Valley, M.P., Tichy, S.E. and Fitzpatrick, P.F. Establishing the kinetic competency of the cationic imine intermediate in nitroalkane oxidase. J. Am. Chem. Soc. 127 (2005) 2062-2066. [PMID: 15713081]

[EC 1.7.3.1 created 1961, modified 2006]

*EC 1.13.11.32

Accepted name: 2-nitropropane dioxygenase

Reaction: 2 2-nitropropane + O2 = 2 acetone + 2 nitrite

Systematic name: 2-nitropropane:oxygen 2-oxidoreductase

Comments: While the enzyme from the fungus Neurospora crassa contains non-covalently bound FMN as the cofactor, that from the yeast Williopsis mrakii contains FAD [2]. This enzyme differs from EC 1.7.3.1, nitroalkane oxidase, in that the preferred substrates are anionic nitronates rather than neutral nitroalkanes [2,3]. The enzyme has broad substrate specificity that is independent of substrate size [2,3]. Some other nitroalkanes, including nitroethane, 1-nitropropane and 3-nitropentan-2-ol, can act as donors, but more slowly.

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, UM-BBD, CAS registry number: 65802-82-6, 61584-55-2

References:

1. Kido, T., Soda, K., Suzuki, T. and Asada, K. A new oxygenase, 2-nitropropane dioxygenase of Hansenula mrakii. Enzymologic and spectrophotometric properties. J. Biol. Chem. 251 (1976) 6994-7000. [PMID: 11214]

2. Ha, J.Y., Min, J.Y., Lee, S.K., Kim, H.S., Kim do, J., Kim, K.H., Lee, H.H., Kim, H.K., Yoon, H.J. and Suh, S.W. Crystal structure of 2-nitropropane dioxygenase complexed with FMN and substrate. Identification of the catalytic base. J. Biol. Chem. 281 (2006) 18660-18667. [PMID: 16682407]

3. Francis, K., Russell, B. and Gadda, G. Involvement of a flavosemiquinone in the enzymatic oxidation of nitroalkanes catalyzed by 2-nitropropane dioxygenase. J. Biol. Chem. 280 (2005) 5195-5204. [PMID: 15582992]

[EC 1.13.11.32 created 1984, modified 2006]

*EC 2.1.1.69

Accepted name: 5-hydroxyfuranocoumarin 5-O-methyltransferase

Reaction: (1) S-adenosyl-L-methionine + a 5-hydroxyfurocoumarin = S-adenosyl-L-homocysteine + a 5- methoxyfurocoumarin (general reaction)
(2) S-adenosyl-L-methionine + bergaptol = S-adenosyl-L-homocysteine + bergapten

For diagram click here.

Glossary: bergaptol = 5-hydroxypsoralen
O-methylbergaptol = bergapten = 5-methoxypsoralen

Other name(s): furanocoumarin 5-methyltransferase; furanocoumarin 5-O-methyltransferase; bergaptol 5-O-methyltransferase; bergaptol O-methyltransferase; bergaptol methyltransferase; S-adenosyl-L-methionine:bergaptol O-methyltransferase; BMT; S-adenosyl-L-methionine:5-hydroxyfuranocoumarin 5-O-methyltransferase

Systematic name: S-adenosyl-L-methionine:5-hydroxyfurocoumarin 5-O-methyltransferase

Comments: Converts bergaptol into bergapten, which has therapeutic potential in the treatment of psoriasis as it has photosensitizing and antiproliferative activities [4]. The enzyme methylates the 5-hydroxy group of some hydroxy- and methylcoumarins, but has little activity on non-coumarin phenols [1]. Caffeate, 5-hydroxyferulate and daphnetin are not substrates [4]. Cu2+, Zn2+ and Co2+ cause enzyme inhibition [4]. (see also EC 2.1.1.70, 8-hydroxyfuranocoumarin 8-O-methyltransferase)

Links to other databases: BRENDA, EXPASY, KEGG, ERGO, CAS registry number: 67339-12-2

References:

1. Thompson, H.J., Sharma, S.K. and Brown, S.A. O-Methyltransferases of furanocoumarin biosynthesis. Arch. Biochem. Biophys. 188 (1978) 272-281. [PMID: 28084]

2. Sharma, S.K., Garrett, J.M. and Brown, S.A. Separation of the S-adenosylmethionine: 5- and 8-hydroxyfuranocoumarin O-methyltransferases of Ruta graveolens L. by general ligand affinity chromatography. Z. Naturforsch. [C] 34C (1979) 387-391. [PMID: 156999]

3. Hauffe, K.D., Hahlbrock, K. and Scheel, D. Elicitor-stimulated furanocoumarin biosynthesis in cultured parsley cells - S-adenosyl-L-methionine-bergaptol and S-adenosyl-L-methionine-xanthotoxol O-methyltransferases. Z. Naturforsch. C: Biosci. 41 (1986) 228-239.

4. Hehmann, M., Lukacin, R., Ekiert, H. and Matern, U. Furanocoumarin biosynthesis in Ammi majus L. Cloning of bergaptol O-methyltransferase. Eur. J. Biochem. 271 (2004) 932-940. [PMID: 15009205]

[EC 2.1.1.69 created 1984 (EC 2.1.1.92 created 1989, incorporated 2006), modified 2006]

*EC 2.1.1.70

Accepted name: 8-hydroxyfuranocoumarin 8-O-methyltransferase

Reaction: (1) S-adenosyl-L-methionine + an 8-hydroxyfurocoumarin = S-adenosyl-L-homocysteine + an 8-methoxyfurocoumarin (general reaction)
(2) S-adenosyl-L-methionine + xanthotoxol = S-adenosyl-L-homocysteine + xanthotoxin

For diagram click here.

Other name(s): furanocoumarin 8-methyltransferase; furanocoumarin 8-O-methyl-transferase; xanthotoxol 8-O-methyltransferase; XMT; S-adenosyl-L-methionine:8-hydroxyfuranocoumarin 8-O-methyltransferase

Systematic name: S-adenosyl-L-methionine:8-hydroxyfurocoumarin 8-O-methyltransferase

Comments: Converts xanthotoxol into xanthotoxin, which has therapeutic potential in the treatment of psoriasis as it has photosensitizing and antiproliferative activities [4]. Methylates the 8-hydroxy group of some hydroxy- and methylcoumarins, but has little activity on non-coumarin phenols. (see also EC 2.1.1.69, 5-hydroxyfuranocoumarin 5-O-methyltransferase)

Links to other databases: BRENDA, EXPASY, KEGG, ERGO, CAS registry number: 67339-13-3

References:

1. Thompson, H.J., Sharma, S.K. and Brown, S.A. O-Methyltransferases of furanocoumarin biosynthesis. Arch. Biochem. Biophys. 188 (1978) 272-281. [PMID: 28084]

2. Sharma, S.K., Garrett, J.M. and Brown, S.A. Separation of the S-adenosylmethionine: 5- and 8-hydroxyfuranocoumarin O-methyltransferases of Ruta graveolens L. by general ligand affinity chromatography. Z. Naturforsch. [C] 34C (1979) 387-391. [PMID: 156999]

3. Hauffe, K.D., Hahlbrock, K. and Scheel, D. Elicitor-stimulated furanocoumarin biosynthesis in cultured parsley cells - S-adenosyl-L-methionine-bergaptol and S-adenosyl-L-methionine-xanthotoxol O-methyltransferases. Z. Naturforsch. C: Biosci. 41 (1986) 228-239.

4. Hehmann, M., Lukacin, R., Ekiert, H. and Matern, U. Furanocoumarin biosynthesis in Ammi majus L. Cloning of bergaptol O-methyltransferase. Eur. J. Biochem. 271 (2004) 932-940. [PMID: 15009205]

[EC 2.1.1.70 created 1984, modified 2006]

[EC 2.1.1.92 Deleted entry: bergaptol O-methyltransferase. Now included with EC 2.1.1.69, 5-hydroxyfuranocoumarin 5-O-methyltransferase. The reaction with bergaptol is a specific example of the general reaction associated with EC 2.1.1.69. (EC 2.1.1.92 created 1989, deleted 2006)]

EC 2.7.7.64

Accepted name: UTP-monosaccharide-1-phosphate uridylyltransferase

Reaction: UTP + a monosaccharide 1-phosphate = diphosphate + UDP-monosaccharide

Glossary: UDP-Xyl = UDP-α-D-xylose
UDP-L-Ara = UDP-β-L-arabinopyranose

Other name(s): UDP-sugar pyrophosphorylase; PsUSP

Comments: Requires Mg2+ or Mn2+ for maximal activity. The reaction can occur in either direction and it has been postulated that MgUTP and Mg-diphosphate are the actual substrates [1,2]. The enzyme catalyses the formation of UDP-Glc, UDP-Gal, UDP-GlcA, UDP-L-Ara and UDP-Xyl, showing broad substrate specificity towards monosaccharide 1-phosphates. Mannose 1-phosphate, L-fucose 1-phosphate and glucose 6-phosphate are not substrates and UTP cannot be replaced by other nucleotide triphosphates [1].

References:

1. Kotake, T., Yamaguchi, D., Ohzono, H., Hojo, S., Kaneko, S., Ishida, H.K. and Tsumuraya, Y. UDP-sugar pyrophosphorylase with broad substrate specificity toward various monosaccharide 1-phosphates from pea sprouts. J. Biol. Chem. 279 (2004) 45728-45736. [PMID: 15326166]

2. Rudick, V.L. and Weisman, R.A. Uridine diphosphate glucose pyrophosphorylase of Acanthamoeba castellanii. Purification, kinetic, and developmental studies. J. Biol. Chem. 249 (1974) 7832-7840. [PMID: 4430676]

[EC 2.7.7.64 created 2006]

EC 2.7.8.27

Accepted name: sphingomyelin synthase

Reaction: a ceramide + a phosphatidylcholine = a sphingomyelin + a 1,2-diacyl-sn-glycerol

For diagram click here.

Glossary: sphingomyelin = a ceramide-1-phosphocholine
ceramide = an N-acylsphingoid. The fatty acids of naturally occurring ceramides range in chain length from about C16 to about C26 and may contain one or more double bonds and/or hydroxy substituents at C-2
sphingoid = sphinganine, i.e. D-erythro-2-aminooctadecane-1,3-diol, and its homologues and stereoisomers (see also Lip-1.4)

Other name(s): SM synthase; SMS1; SMS2

Systematic name: ceramide:phosphatidylcholine cholinephosphotransferase

Comments: The reaction can occur in both directions [3]. This enzyme occupies a central position in sphingolipid and glycerophospholipid metabolism [4]. Up- and down-regulation of its activity has been linked to mitogenic and pro-apoptotic signalling in a variety of mammalian cell types [4]. Unlike EC 2.7.8.3, ceramide cholinephosphotransferase, CDP-choline cannot replace phosphatidylcholine as the donor of the phosphocholine moiety of sphingomyelin [2].

References:

1. Ullman, M.D. and Radin, N.S. The enzymatic formation of sphingomyelin from ceramide and lecithin in mouse liver. J. Biol. Chem. 249 (1974) 1506-1512. [PMID: 4817756]

2. Voelker, D.R. and Kennedy, E.P. Cellular and enzymic synthesis of sphingomyelin. Biochemistry 21 (1982) 2753-2759. [PMID: 7093220]

3. Huitema, K., van den Dikkenberg, J., Brouwers, J.F. and Holthuis, J.C. Identification of a family of animal sphingomyelin synthases. EMBO J. 23 (2004) 33-44. [PMID: 14685263]

4. Tafesse, F.G., Ternes, P. and Holthuis, J.C. The multigenic sphingomyelin synthase family. J. Biol. Chem. 281 (2006) 29421-29425. [PMID: 16905542]

5. Yamaoka, S., Miyaji, M., Kitano, T., Umehara, H. and Okazaki, T. Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells. J. Biol. Chem. 279 (2004) 18688-18693. [PMID: 14976195]

[EC 2.7.8.27 created 2006]

EC 3.4.13.22

Accepted name: D-Ala-D-Ala dipeptidase

Reaction: D-Ala-D-Ala + H2O = 2 D-Ala

Other name(s): D-alanyl-D-alanine dipeptidase; vanX D-Ala-D-Ala dipeptidase; VanX

Comments: A Zn2+-dependent enzyme [4]. The enzyme protects Enterococcus faecium from the antibiotic vancomycin, which can bind to the -D-Ala-D-Ala sequence at the C-terminus of the peptidoglycan pentapeptide (see diagram). This enzyme reduces the availability of the free dipeptide D-Ala-D-Ala, which is the precursor for this pentapeptide sequence, allowing D-Ala-(R)-lactate (for which vancomycin has much less affinity) to be added to the cell wall instead [2,3]. The enzyme is stereospecific, as L-Ala-L-Ala, D-Ala-L-Ala and L-Ala-D-Ala are not substrates [2]. Belongs in peptidase family M15.

Links to other databases: BRENDA, EXPASY, KEGG, ERGO, CAS registry number:

References:

1. Reynolds, P.E., Depardieu, F., Dutka-Malen, S., Arthur, M. and Courvalin, P. Glycopeptide resistance mediated by enterococcal transposon Tn1546 requires production of VanX for hydrolysis of D-alanyl-D-alanine. Mol. Microbiol. 13 (1994) 1065-1070. [PMID: 7854121]

2. Wu, Z., Wright, G.D. and Walsh, C.T. Overexpression, purification, and characterization of VanX, a D-, D-dipeptidase which is essential for vancomycin resistance in Enterococcus faecium BM4147. Biochemistry 34 (1995) 2455-2463. [PMID: 7873524]

3. McCafferty, D.G., Lessard, I.A. and Walsh, C.T. Mutational analysis of potential zinc-binding residues in the active site of the enterococcal D-Ala-D-Ala dipeptidase VanX. Biochemistry 36 (1997) 10498-10505. [PMID: 9265630]

4. Bussiere, D.E., Pratt, S.D., Katz, L., Severin, J.M., Holzman, T. and Park, C.H. The structure of VanX reveals a novel amino-dipeptidase involved in mediating transposon-based vancomycin resistance. Mol. Cell. 2 (1998) 75-84. [PMID: 9702193]

5. Tan, A.L., Loke, P. and Sim, T.S. Molecular cloning and functional characterisation of VanX, a D-alanyl-D-alanine dipeptidase from Streptomyces coelicolor A3(2). Res. Microbiol. 153 (2002) 27-32. [PMID: 11881895]

6. Matthews, M.L., Periyannan, G., Hajdin, C., Sidgel, T.K., Bennett, B. and Crowder, M.W. Probing the reaction mechanism of the D-ala-D-ala dipeptidase, VanX, by using stopped-flow kinetic and rapid-freeze quench EPR studies on the Co(II)-substituted enzyme. J. Am. Chem. Soc. 128 (2006) 13050-13051. [PMID: 17017774]

[EC 3.4.13.22 created 2006]

EC 3.5.2.18

Accepted name: enamidase

Reaction: 6-oxo-1,4,5,6-tetrahydronicotinate + 2 H2O = 2-formylglutarate + NH3

For diagram click here.

Systematic name: 6-oxo-1,4,5,6-tetrahydronicotinate amidohydrolase

Comments: Contains iron and Zn2+. Forms part of the nicotinate-fermentation catabolism pathway in Eubacterium barkeri. Other enzymes involved in this pathway are EC 1.17.1.5 (nicotinate dehydrogenase), EC 1.3.7.1 (6-hydroxynicotinate reductase), EC 1.1.1.291 (2-hydroxymethylglutarate dehydrogenase), EC 5.4.99.4 (2-methyleneglutarate mutase), EC 5.3.3.6 (methylitaconate Δ-isomerase), EC 4.2.1.85 (dimethylmaleate hydratase) and EC 4.1.3.32 (2,3-dimethylmalate lyase).

References:

1. Alhapel, A., Darley, D.J., Wagener, N., Eckel, E., Elsner, N. and Pierik, A.J. Molecular and functional analysis of nicotinate catabolism in Eubacterium barkeri. Proc. Natl. Acad. Sci. USA 103 (2006) 12341-12346. [PMID: 16894175]

[EC 3.5.2.18 created 2006]

EC 4.2.1.110

Accepted name: aldos-2-ulose dehydratase

Reaction: 1,5-anhydro-D-fructose = 2-hydroxy-2-(hydroxymethyl)-2H-pyran-3(6H)-one + H2O (overall reaction)
(1a) 1,5-anhydro-D-fructose = 1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulose + H2O
(1b) 1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulose = 2-hydroxy-2-(hydroxymethyl)-2H-pyran-3(6H)-one

For diagram click here.

Glossary: 1,5-anhydro-D-fructose = 1,5-anhydro-D-arabino-hex-2-ulose = (4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)dihydro-2H-pyran-3(4H)-one
ascopyrone M = 1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulose = (6S)-4-hydroxy-6-(hydroxymethyl)-2H-pyran-3(6H)-one
microthecin = 2-hydroxy-2-(hydroxymethyl)-2H-pyran-3(6H)-one

Other name(s): pyranosone dehydratase; AUDH; 1,5-anhydro-D-fructose dehydratase (microthecin-forming)

Systematic name: 1,5-anhydro-D-fructose hydro-lyase (microthecin-forming)

Comments: This enzyme catalyses two of the steps in the anhydrofructose pathway, which leads to the degradation of glycogen and starch via 1,5-anhydro-D-fructose [1,2]. The other enzymes involved in this pathway are EC 4.2.1.111 (1,5-anhydro-D-fructose dehydratase), EC 4.2.2.13 (exo-(1→4)-α-D-glucan lyase) and EC 5.3.3.15 (ascopyrone tautomerase). Aldose-2-uloses such as 2-dehydroglucose can also act as substrates, but more slowly [1,2,4]. This is a bifunctional enzyme that acts as both a lyase and as an isomerase [2]. Differs from EC 4.2.1.111, which can carry out only reaction (1a) and requires a cofactor for activity [5].

References:

1. Yu, S. and Fiskesund, R. The anhydrofructose pathway and its possible role in stress response and signaling. Biochim. Biophys. Acta 1760 (2006) 1314-1322. [PMID: 16822618]

2. Yu, S. Enzymatic description of the anhydrofructose pathway of glycogen degradation. II. Gene identification and characterization of the reactions catalyzed by aldos-2-ulose dehydratase that converts 1,5-anhydro-D-fructose to microthecin with ascopyrone M as the intermediate. Biochim. Biophys. Acta 1723 (2005) 63-73. [PMID: 15716041]

3. Broberg, A., Kenne, L. and Pedersén, M. Presence of microthecin in the red alga Gracilariopsis lemaneiformis and its formation from 1,5-anhydro-D-fructose. Phytochemistry 41 (1996) 151-154.

4. Gabriel, J., Volc, J., Sedmera, P., Daniel, G. and Kubátová, E. Pyranosone dehydratase from the basidiomycete Phanerochaete chrysosporium: improved purification, and identification of 6-deoxy-D-glucosone and D-xylosone reaction products. Arch. Microbiol. 160 (1993) 27-34. [PMID: 8352649]

5. Yu, S., Refdahl, C. and Lundt, I. Enzymatic description of the anhydrofructose pathway of glycogen degradation; I. Identification and purification of anhydrofructose dehydratase, ascopyrone tautomerase and α-1,4-glucan lyase in the fungus Anthracobia melaloma. Biochim. Biophys. Acta 1672 (2004) 120-129. [PMID: 15110094]

[EC 4.2.1.110 created 2006]

EC 4.2.1.111

Accepted name: 1,5-anhydro-D-fructose dehydratase

Reaction: 1,5-anhydro-D-fructose = 1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulose + H2O

For diagram click here.

Glossary: 1,5-anhydro-D-fructose = 1,5-anhydro-D-arabino-hex-2-ulose = (4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)dihydro-2H-pyran-3(4H)-one
ascopyrone M = 1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulose = 4-hydroxy-6-(hydroxymethyl)-2H-pyran-3(6H)-one

Other name(s): 1,5-anhydro-D-fructose 4-dehydratase; 1,5-anhydro-D-fructose hydrolyase; 1,5-anhydro-D-arabino-hex-2-ulose dehydratase; AFDH; AF dehydratase

Systematic name: 1,5-anhydro-D-fructose hydro-lyase

Comments: This enzyme catalyses one of the steps in the anhydrofructose pathway, which leads to the degradation of glycogen and starch via 1,5-anhydro-D-fructose [1,2]. The other enzymes involved in this pathway are EC 4.2.1.110 (aldos-2-ulose dehydratase), EC 4.2.2.13 [exo-(1→4)-α-D-glucan lyase] and EC 5.3.3.15 (ascopyrone tautomerase). Requires divalent (Ca2+ or Mg2+) or monovalent cations (Na+) for optimal activity. Unlike EC 4.2.1.110, aldos-2-ulose dehydratase, the enzyme is specific for 1,5-anhydro-D-fructose as substrate and shows no activity towards aldose-2-uloses such as 2-dehydroglucose [1,2,3]. In addition, it is inhibited by its end-product ascopyrone M [2] and it cannot convert ascopyrone M into microthecin, as can EC 4.2.1.110.

References:

1. Yu, S., Refdahl, C. and Lundt, I. Enzymatic description of the anhydrofructose pathway of glycogen degradation; I. Identification and purification of anhydrofructose dehydratase, ascopyrone tautomerase and α-1,4-glucan lyase in the fungus Anthracobia melaloma. Biochim. Biophys. Acta 1672 (2004) 120-129. [PMID: 15110094]

2. Yu, S. and Fiskesund, R. The anhydrofructose pathway and its possible role in stress response and signaling. Biochim. Biophys. Acta 1760 (2006) 1314-1322. [PMID: 16822618]

3. Yu, S. Enzymatic description of the anhydrofructose pathway of glycogen degradation. II. Gene identification and characterization of the reactions catalyzed by aldos-2-ulose dehydratase that converts 1,5-anhydro-D-fructose to microthecin with ascopyrone M as the intermediate. Biochim. Biophys. Acta 1723 (2005) 63-73. [PMID: 15716041]

[EC 4.2.1.111 created 2006]

EC 5.3.3.15

Accepted name: ascopyrone tautomerase

Reaction: 1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulose = 1,5-anhydro-4-deoxy-D-glycero-hex-1-en-3-ulose

For diagram click here.

Glossary: ascopyrone M = 1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulose = 4-hydroxy-6-(hydroxymethyl)-2H-pyran-3(6H)-one
ascopyrone P = 1,5-anhydro-4-deoxy-D-glycero-hex-1-en-3-ulose = 5-hydroxy-2-(hydroxymethyl)-2H-pyran-4(3H)-one

Other name(s): ascopyrone isomerase; ascopyrone intramolecular oxidoreductase; 1,5-anhydro-D-glycero-hex-3-en-2-ulose tautomerase; APM tautomerase; ascopyrone P tautomerase; APTM

Systematic name: 1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulose Δ31-isomerase

Comments: This enzyme catalyses one of the steps in the anhydrofructose pathway, which leads to the degradation of glycogen and starch via 1,5-anhydro-D-fructose [1,2]. The other enzymes involved in this pathway are EC 4.2.1.110 (aldos-2-ulose dehydratase), EC 4.2.1.111 (1,5-anhydro-D-fructose dehydratase) and EC 4.2.2.13 [exo-(1→4)-α-D-glucan lyase]. Ascopyrone P is an anti-oxidant [2].

References:

1. Yu, S., Refdahl, C. and Lundt, I. Enzymatic description of the anhydrofructose pathway of glycogen degradation; I. Identification and purification of anhydrofructose dehydratase, ascopyrone tautomerase and α-1,4-glucan lyase in the fungus Anthracobia melaloma. Biochim. Biophys. Acta 1672 (2004) 120-129. [PMID: 15110094]

2. Yu, S. and Fiskesund, R. The anhydrofructose pathway and its possible role in stress response and signaling. Biochim. Biophys. Acta 1760 (2006) 1314-1322. [PMID: 16822618]

[EC 5.3.3.15 created 2006]

EC 6.3.1.12

Accepted name: D-aspartate ligase

Reaction: ATP + D-aspartate + [β-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)]n = [β-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-6-N-(β-D-Asp)-L-Lys-D-Ala-D-Ala)]n + ADP + phosphate

For diagram click here.

Other name(s): Aslfm; UDP-MurNAc-pentapeptide:D-aspartate ligase; D-aspartic acid-activating enzyme

Systematic name: D-aspartate:[β-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)]n ligase (ADP-forming)

Comments: This enzyme forms part of the peptidoglycan assembly pathway of Gram-positive bacteria grown in medium containing D-Asp. Normally, the side chains the acylate the 6-amino group of the L-lysine residue contain L-Ala-L-Ala but these amino acids are replaced by D-Asp when D-Asp is included in the medium. Hybrid chains containing L-Ala-D-Asp, L-Ala-L-Ala-D-Asp or D-Asp-L-Ala are not formed [4]. The enzyme belongs in the ATP-grasp protein superfamily [3,4]. The enzyme is highly specific for D-aspartate, as L-aspartate, D-glutamate, D-alanine, D-iso-asparagine and D-malic acid are not substrates [4]. In Enterococcus faecium, the substrate D-aspartate is produced by EC 5.1.1.13, aspartate racemase [4]

References:

1. Staudenbauer, W. and Strominger, J.L. Activation of D-aspartic acid for incorporation into peptidoglycan. J. Biol. Chem. 247 (1972) 5095-5102. [PMID: 4262567]

2. Staudenbauer, W., Willoughby, E. and Strominger, J.L. Further studies of the D-aspartic acid-activating enzyme of Streptococcus faecalis and its attachment to the membrane. J. Biol. Chem. 247 (1972) 5289-5296. [PMID: 4626717]

3. Galperin, M.Y. and Koonin, E.V. A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity. Protein Sci. 6 (1997) 2639-2643. [PMID: 9416615]

4. Bellais, S., Arthur, M., Dubost, L., Hugonnet, J.E., Gutmann, L., van Heijenoort, J., Legrand, R., Brouard, J.P., Rice, L. and Mainardi, J.L. Aslfm, the D-aspartate ligase responsible for the addition of D-aspartic acid onto the peptidoglycan precursor of Enterococcus faecium. J. Biol. Chem. 281 (2006) 11586-11594. [PMID: 16510449]

[EC 6.3.1.12 created 2006]

EC 6.4.1.7

Accepted name: 2-oxoglutarate carboxylase

Reaction: ATP + 2-oxoglutarate + HCO3- = ADP + phosphate + oxalosuccinate

For diagram click here.

Glossary: oxalosuccinate = 1-oxopropane-1,2,3-tricarboxylate

Other name(s): oxalosuccinate synthetase; carboxylating factor for ICDH (incorrect); CFI; OGC

Comments: A biotin-containing enzyme that requires Mg2+ for activity. It was originally thought [1] that this enzyme was a promoting factor for the carboxylation of 2-oxoglutarate by EC 1.1.1.41, isocitrate dehydrogenase (NAD+), but this has since been disproved [2]. The product of the reaction is unstable and is quickly converted into isocitrate by the action of EC 1.1.1.41 [2].

References:

1. Aoshima, M., Ishii, M. and Igarashi, Y. A novel biotin protein required for reductive carboxylation of 2-oxoglutarate by isocitrate dehydrogenase in Hydrogenobacter thermophilus TK-6. Mol. Microbiol. 51 (2004) 791-798. [PMID: 14731279]

2. Aoshima, M. and Igarashi, Y. A novel oxalosuccinate-forming enzyme involved in the reductive carboxylation of 2-oxoglutarate in Hydrogenobacter thermophilus TK-6. Mol. Microbiol. 62 (2006) 748-759. [PMID: 17076668]

[EC 6.4.1.7 created 2006]


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