EC |
1.4.1.21 |
Accepted name: |
aspartate dehydrogenase |
Reaction: |
L-aspartate + H2O + NAD(P)+ = oxaloacetate + NH3 + NAD(P)H + H+ (overall reaction) (1a) L-aspartate + NAD(P)+ = 2-iminosuccinate + NAD(P)H + H+ (1b) 2-iminosuccinate + H2O = oxaloacetate + NH3 (spontaneous) |
Other name(s): |
AspDH; NAD-dependent aspartate dehydrogenase; NADH2-dependent aspartate dehydrogenase; NADP+-dependent aspartate dehydrogenase; nadX (gene name); L-aspartate:NAD(P)+ oxidoreductase (deaminating) |
Systematic name: |
L-aspartate:NAD(P)+ oxidoreductase (2-iminosuccinate-forming) |
Comments: |
The enzyme is strictly specific for L-aspartate as substrate. It produces the unstable compound 2-iminosuccinate, which, in the presence of water, hydrolyses spontaneously to form oxaloacetate. The enzyme from some archaea and thermophilic bacteria is likely to transfer 2-iminosuccinate directly to EC 2.5.1.72, quinolinate synthase, preventing its hydrolysis and enabling the de novo biosynthesis of NAD+. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37278-97-0 |
References: |
1. |
Kretovich, W.L., Kariakina, T.I., Weinova, M.K., Sidelnikova, L.I. and Kazakova, O.W. The synthesis of aspartic acid in Rhizobium lupini bacteroids. Plant Soil 61 (1981) 145–156. |
2. |
Okamura, T., Noda, H., Fukuda, S. and Ohsugi, M. Aspartate dehydrogenase in vitamin B12-producing Klebsiella pneumoniae IFO 13541. J. Nutr. Sci. Vitaminol. 44 (1998) 483–490. [PMID: 9819709] |
3. |
Yang, Z., Savchenko, A., Yakunin, A., Zhang, R., Edwards, A., Arrowsmith, C. and Tong, L. Aspartate dehydrogenase, a novel enzyme identified from structural and functional studies of TM1643. J. Biol. Chem. 278 (2003) 8804–8808. [DOI] [PMID: 12496312] |
4. |
Yoneda, K., Kawakami, R., Tagashira, Y., Sakuraba, H., Goda, S. and Ohshima, T. The first archaeal L-aspartate dehydrogenase from the hyperthermophile Archaeoglobus fulgidus: gene cloning and enzymological characterization. Biochim. Biophys. Acta 1764 (2006) 1087–1093. [DOI] [PMID: 16731057] |
5. |
Yoneda, K., Sakuraba, H., Tsuge, H., Katunuma, N. and Ohshima, T. Crystal structure of archaeal highly thermostable L-aspartate dehydrogenase/NAD/citrate ternary complex. FEBS J. 274 (2007) 4315–4325. [DOI] [PMID: 17651440] |
6. |
Li, Y., Kawakami, N., Ogola, H.J., Ashida, H., Ishikawa, T., Shibata, H. and Sawa, Y. A novel L-aspartate dehydrogenase from the mesophilic bacterium Pseudomonas aeruginosa PAO1: molecular characterization and application for L-aspartate production. Appl. Microbiol. Biotechnol. 90 (2011) 1953–1962. [DOI] [PMID: 21468714] |
7. |
Li, Y., Ishida, M., Ashida, H., Ishikawa, T., Shibata, H. and Sawa, Y. A non-NadB type L-aspartate dehydrogenase from Ralstonia eutropha strain JMP134: molecular characterization and physiological functions. Biosci. Biotechnol. Biochem. 75 (2011) 1524–1532. [DOI] [PMID: 21821928] |
8. |
Li, Y., Ogola, H.J. and Sawa, Y. L-aspartate dehydrogenase: features and applications. Appl. Microbiol. Biotechnol. 93 (2012) 503–516. [DOI] [PMID: 22120624] |
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[EC 1.4.1.21 created 2005, modified 2022] |
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EC |
1.4.3.16 |
Accepted name: |
L-aspartate oxidase |
Reaction: |
L-aspartate + O2 = iminosuccinate + H2O2 |
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For diagram of quinolinate biosynthesis, click here |
Other name(s): |
NadB; Laspo; AO |
Systematic name: |
L-aspartate:oxygen oxidoreductase |
Comments: |
A flavoprotein (FAD). L-Aspartate oxidase catalyses the first step in the de novo biosynthesis of NAD+ in some bacteria. O2 can be replaced by fumarate as electron acceptor, yielding succinate [5]. The ability of the enzyme to use both O2 and fumarate in cofactor reoxidation enables it to function under both aerobic and anaerobic conditions [5]. Iminosuccinate can either be hydrolysed to form oxaloacetate and NH3 or can be used by EC 2.5.1.72, quinolinate synthase, in the production of quinolinate. The enzyme is a member of the succinate dehydrogenase/fumarate-reductase family of enzymes [5]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 69106-47-4 |
References: |
1. |
Nasu, S., Wicks, F.D. and Gholson, R.K. L-Aspartate oxidase, a newly discovered enzyme of Escherichia coli, is the B protein of quinolinate synthetase. J. Biol. Chem. 257 (1982) 626–632. [PMID: 7033218] |
2. |
Mortarino, M., Negri, A., Tedeschi, G., Simonic, T., Duga, S., Gassen, H.G. and Ronchi, S. L-Aspartate oxidase from Escherichia coli. I. Characterization of coenzyme binding and product inhibition. Eur. J. Biochem. 239 (1996) 418–426. [DOI] [PMID: 8706749] |
3. |
Tedeschi, G., Negri, A., Mortarino, M., Ceciliani, F., Simonic, T., Faotto, L. and Ronchi, S. L-Aspartate oxidase from Escherichia coli. II. Interaction with C4 dicarboxylic acids and identification of a novel L-aspartate: fumarate oxidoreductase activity. Eur. J. Biochem. 239 (1996) 427–433. [DOI] [PMID: 8706750] |
4. |
Mattevi, A., Tedeschi, G., Bacchella, L., Coda, A., Negri, A. and Ronchi, S. Structure of L-aspartate oxidase: implications for the succinate dehydrogenase/fumarate reductase oxidoreductase family. Structure 7 (1999) 745–756. [DOI] [PMID: 10425677] |
5. |
Bossi, R.T., Negri, A., Tedeschi, G. and Mattevi, A. Structure of FAD-bound L-aspartate oxidase: insight into substrate specificity and catalysis. Biochemistry 41 (2002) 3018–3024. [DOI] [PMID: 11863440] |
6. |
Katoh, A., Uenohara, K., Akita, M. and Hashimoto, T. Early steps in the biosynthesis of NAD in Arabidopsis start with aspartate and occur in the plastid. Plant Physiol. 141 (2006) 851–857. [DOI] [PMID: 16698895] |
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[EC 1.4.3.16 created 1984, modified 2008] |
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EC |
2.4.2.19 |
Accepted name: |
nicotinate-nucleotide diphosphorylase (carboxylating) |
Reaction: |
β-nicotinate D-ribonucleotide + diphosphate + CO2 = pyridine-2,3-dicarboxylate + 5-phospho-α-D-ribose 1-diphosphate |
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For diagram of NAD+ biosynthesis, click here |
Glossary: |
quinolinate = pyridine-2,3-dicarboxylate |
Other name(s): |
quinolinate phosphoribosyltransferase (decarboxylating); quinolinic acid phosphoribosyltransferase; QAPRTase; NAD+ pyrophosphorylase; nicotinate mononucleotide pyrophosphorylase (carboxylating); quinolinic phosphoribosyltransferase |
Systematic name: |
β-nicotinate-D-ribonucleotide:diphosphate phospho-α-D-ribosyltransferase (carboxylating) |
Comments: |
The reaction is catalysed in the opposite direction. Since quinolinate is synthesized from L-tryptophan in eukaryotes, but from L-aspartate in some prokaryotes, this is the first NAD+ biosynthesis enzyme shared by both eukaryotes and prokaryotes [3]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37277-74-0 |
References: |
1. |
Gholson, R.K., Ueda, I., Ogasawara, N. and Henderson, L.M. The enzymatic conversion of quinolinate to nicotinic acid mononucleotide in mammalian liver. J. Biol. Chem. 239 (1964) 1208–1214. [PMID: 14165928] |
2. |
Packman, P.M. and Jakoby, W.B. Crystalline quinolinate phosphoribosyltransferase. J. Biol. Chem. 240 (1965) 4107–4108. [PMID: 5320648] |
3. |
Katoh, A., Uenohara, K., Akita, M. and Hashimoto, T. Early steps in the biosynthesis of NAD in Arabidopsis start with aspartate and occur in the plastid. Plant Physiol. 141 (2006) 851–857. [DOI] [PMID: 16698895] |
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[EC 2.4.2.19 created 1972] |
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EC |
2.5.1.72 |
Accepted name: |
quinolinate synthase |
Reaction: |
glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate |
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For diagram of quinolinate biosynthesis, click here |
Glossary: |
quinolinate = pyridine-2,3-dicarboxylate
glycerone phosphate = dihydroxyacetone phosphate = 3-hydroxy-2-oxopropyl phosphate |
Other name(s): |
NadA; QS; quinolinate synthetase |
Systematic name: |
glycerone phosphate:iminosuccinate alkyltransferase (cyclizing) |
Comments: |
An iron-sulfur protein that requires a [4Fe-4S] cluster for activity [1]. Quinolinate synthase catalyses the second step in the de novo biosynthesis of NAD+ from aspartate in some bacteria, with EC 1.4.3.16 (L-aspartate oxidase) catalysing the first step and EC 2.4.2.19 [nicotinate-nucleotide diphosphorylase (carboxylating)] the third step. In Escherichia coli, two of the residues that are involved in the [4Fe-4S] cluster binding appear to undergo reversible disulfide-bond formation that regulates the activity of the enzyme [5]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Ollagnier-de Choudens, S., Loiseau, L., Sanakis, Y., Barras, F. and Fontecave, M. Quinolinate synthetase, an iron-sulfur enzyme in NAD biosynthesis. FEBS Lett. 579 (2005) 3737–3743. [DOI] [PMID: 15967443] |
2. |
Katoh, A., Uenohara, K., Akita, M. and Hashimoto, T. Early steps in the biosynthesis of NAD in Arabidopsis start with aspartate and occur in the plastid. Plant Physiol. 141 (2006) 851–857. [DOI] [PMID: 16698895] |
3. |
Sakuraba, H., Tsuge, H., Yoneda, K., Katunuma, N. and Ohshima, T. Crystal structure of the NAD biosynthetic enzyme quinolinate synthase. J. Biol. Chem. 280 (2005) 26645–26648. [DOI] [PMID: 15937336] |
4. |
Rousset, C., Fontecave, M. and Ollagnier de Choudens, S. The [4Fe-4S] cluster of quinolinate synthase from Escherichia coli: Investigation of cluster ligands. FEBS Lett. 582 (2008) 2937–2944. [DOI] [PMID: 18674537] |
5. |
Saunders, A.H. and Booker, S.J. Regulation of the activity of Escherichia coli quinolinate synthase by reversible disulfide-bond formation. Biochemistry 47 (2008) 8467–8469. [DOI] [PMID: 18651751] |
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[EC 2.5.1.72 created 2008] |
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