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Pathway Description
NAD Biosynthesis
Escherichia coli
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2015-03-30
Last Updated: 2019-09-03
Nicotinamide adenine dinucleotide (NAD) can be biosynthesized from L-aspartic acid. This amino acid reacts with oxygen through an L-aspartate oxidase resulting in a hydrogen ion, hydrogen peroxide and an iminoaspartic acid. The latter compound interacts with dihydroxyacetone phosphate through a quinolinate synthase A, resulting in a phosphate, water, and a quinolic acid. Quinolic acid interacts with phosphoribosyl pyrophosphate and hydrogen ion through a quinolinate phosphoribosyltransferase resulting in pyrophosphate, carbon dioxide and nicotinate beta-D-ribonucleotide. The latter is adenylated through an ATP driven nicotinate-mononucleotide adenylyltransferase releasing a pyrophosphate and resulting in a nicotinic acid adenine dinucleotide.
Nicotinic acid adenine dinucleotide is processed through an NAD synthetase, NH3-dependent in two different manners.
In the first case, Nicotinic acid adenine dinucleotide interacts with ATP, L-glutamine and water through the enzyme and results in hydrogen ion, AMP, pyrophosphate, L-glutamic acid and NAD.
In the second case, Nicotinic acid adenine dinucleotide interacts with ATP and ammonium through the enzyme resulting in a pyrophosphate, AMP, hydrogen ion and NAD.
NAD then proceeds to regulate its own pathway by repressing L-aspartate oxidase.
As a general rule, most prokaryotes utilize the aspartate de novo pathway, in which the nicotinate moiety of NAD is synthesized from aspartate , while in eukaryotes, the de novo pathway starts with tryptophan.
References
NAD Biosynthesis References
ANDREOLI AJ, IKEDA M, NISHIZUKA Y, HAYAISHI O: Quinolinic acid: a precursor to nicotinamide adenine dinucleotide in Escherichia coli. Biochem Biophys Res Commun. 1963 Jul 18;12:92-7.
Pubmed: 14013029
Begley TP, Kinsland C, Mehl RA, Osterman A, Dorrestein P: The biosynthesis of nicotinamide adenine dinucleotides in bacteria. Vitam Horm. 2001;61:103-19.
Pubmed: 11153263
Chandler JL, Gholson RK, Scott TA: Studies on the de novo biosynthesis of NAD in Escherichia coli. I. Labelling patterns from precursors. Biochim Biophys Acta. 1970 Nov 24;222(2):523-6.
Pubmed: 4321550
ORTEGA MV, BROWN GM: Precursors of nicotinic acid in Escherichia coli. J Biol Chem. 1960 Oct;235:2939-45.
Pubmed: 13731310
Panozzo C, Nawara M, Suski C, Kucharczyka R, Skoneczny M, Becam AM, Rytka J, Herbert CJ: Aerobic and anaerobic NAD+ metabolism in Saccharomyces cerevisiae. FEBS Lett. 2002 Apr 24;517(1-3):97-102.
Pubmed: 12062417
Rizzi M, Schindelin H: Structural biology of enzymes involved in NAD and molybdenum cofactor biosynthesis. Curr Opin Struct Biol. 2002 Dec;12(6):709-20.
Pubmed: 12504674
Suzuki N, Carlson J, Griffith G, Gholson RK: Studies on the de novo biosynthesis of NAD in Escherichia coli. V. Properties of the quinolinic acid synthetase system. Biochim Biophys Acta. 1973 Apr 28;304(2):309-15.
Pubmed: 4351074
Flachmann R, Kunz N, Seifert J, Gutlich M, Wientjes FJ, Laufer A, Gassen HG: Molecular biology of pyridine nucleotide biosynthesis in Escherichia coli. Cloning and characterization of quinolinate synthesis genes nadA and nadB. Eur J Biochem. 1988 Aug 1;175(2):221-8. doi: 10.1111/j.1432-1033.1988.tb14187.x.
Pubmed: 2841129
Seifert J, Kunz N, Flachmann R, Laufer A, Jany KD, Gassen HG: Expression of the E. coli nadB gene and characterization of the gene product L-aspartate oxidase. Biol Chem Hoppe Seyler. 1990 Mar;371(3):239-48.
Pubmed: 2187483
Mattevi A, Tedeschi G, Bacchella L, Coda A, Negri A, Ronchi S: Structure of L-aspartate oxidase: implications for the succinate dehydrogenase/fumarate reductase oxidoreductase family. Structure. 1999 Jul 15;7(7):745-56.
Pubmed: 10425677
Oshima T, Aiba H, Baba T, Fujita K, Hayashi K, Honjo A, Ikemoto K, Inada T, Itoh T, Kajihara M, Kanai K, Kashimoto K, Kimura S, Kitagawa M, Makino K, Masuda S, Miki T, Mizobuchi K, Mori H, Motomura K, Nakamura Y, Nashimoto H, Nishio Y, Saito N, Horiuchi T, et al.: A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map. DNA Res. 1996 Jun 30;3(3):137-55. doi: 10.1093/dnares/3.3.137.
Pubmed: 8905232
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
Whitchurch CB, Mattick JS: Escherichia coli contains a set of genes homologous to those involved in protein secretion, DNA uptake and the assembly of type-4 fimbriae in other bacteria. Gene. 1994 Dec 2;150(1):9-15. doi: 10.1016/0378-1119(94)90851-6.
Pubmed: 7959070
Bhatia R, Calvo KC: The sequencing expression, purification, and steady-state kinetic analysis of quinolinate phosphoribosyl transferase from Escherichia coli. Arch Biochem Biophys. 1996 Jan 15;325(2):270-8. doi: 10.1006/abbi.1996.0034.
Pubmed: 8561507
Fujita N, Mori H, Yura T, Ishihama A: Systematic sequencing of the Escherichia coli genome: analysis of the 2.4-4.1 min (110,917-193,643 bp) region. Nucleic Acids Res. 1994 May 11;22(9):1637-9. doi: 10.1093/nar/22.9.1637.
Pubmed: 8202364
Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. doi: 10.1038/msb4100049. Epub 2006 Feb 21.
Pubmed: 16738553
Allibert P, Willison JC, Vignais PM: Complementation of nitrogen-regulatory (ntr-like) mutations in Rhodobacter capsulatus by an Escherichia coli gene: cloning and sequencing of the gene and characterization of the gene product. J Bacteriol. 1987 Jan;169(1):260-71. doi: 10.1128/jb.169.1.260-271.1987.
Pubmed: 3025172
Aiba H, Baba T, Hayashi K, Inada T, Isono K, Itoh T, Kasai H, Kashimoto K, Kimura S, Kitakawa M, Kitagawa M, Makino K, Miki T, Mizobuchi K, Mori H, Mori T, Motomura K, Nakade S, Nakamura Y, Nashimoto H, Nishio Y, Oshima T, Saito N, Sampei G, Horiuchi T, et al.: A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 28.0-40.1 min region on the linkage map. DNA Res. 1996 Dec 31;3(6):363-77. doi: 10.1093/dnares/3.6.363.
Pubmed: 9097039
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