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Escherichia coli K-12 substr. MG1655 Pathway: NAD biosynthesis I (from aspartate)

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Synonyms: nicotinamide adenine dinucleotide biosynthesis

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis NAD Metabolism NAD Biosynthesis

Summary:
General Background

Nicotinamide adenine dinucleotide (NAD) and its phosphorylated derivative, nicotinamide adenine dinucleotide phosphate (NADP), are two of the most important coenzymes in redox reactions in the cell. Generally, NAD is involved in catabolic reactions, while NADP is involved in anabolic reactions. Because of the positive charge on the nitrogen atom in the nicotinamide ring, the oxidized forms of these compounds are often depicted as NAD+ and NADP+, respectively.

Most oxidation reactions in cells are accomplished by the removal of hydrogen atoms. In reactions where NAD or NADP participate, two hydrogen atoms are typically removed from the substrate. During the reduction of NAD+ (or NADP+), the molecule acquires two electrons and one proton, while the second proton is released into the medium. Thus a typical reaction involving NAD is in the form:

NAD+ + 2H -> NADH + H+

NAD is synthesized via two major pathway families in both prokaryotic and eukaryotic systems; the de novo pathway, and the salvage pathway.

About This Pathway

As a general rule, most prokaryotes utilize the aspartate de novo pathway, in which the nicotinate moiety of NAD is synthesized from aspartate [Begley01], while in eukaryotes, the de novo pathway starts with tryptophan [Panozzo02] (NAD biosynthesis II (from tryptophan)).

The first attempt to elucidate a prokaryotic pathway to NAD was reported by Ortega and Brown in 1960 [Ortega60]. They implicated (incorrectly) glycerol and a dicarboxylic acid as precursors in the synthesis of the pyridine ring of NAD in E. coli. Subsequent work by Chandler et al. [Chandler70] established that L-aspartate is the dicarboxylic acid precursor. Suzuki et al., in 1973, established that the three carbon precursor is dihydroxyacetone phosphate (DHAP) and not glycerol [Suzuki73]. In addition, Andreoli et al. demonstrated that quinolinate was a key intermediate in this pathway [Andreoli63]. Eventually it became clear that quinolinate is indeed a precursor, not only in this pathway, but in all known NAD biosynthetic pathways.

Reviews: [Begley01, Rizzi02]

Superpathways: aspartate superpathway

Variants: NAD salvage pathway I , NAD salvage pathway II , NAD salvage pathway III

Credits:
Created 31-Jan-1995 by Riley M , Marine Biological Laboratory
Revised 09-May-2005 by Caspi R , SRI International
Reviewed 14-Oct-2006 by Foerster H , TAIR


References

Andreoli63: Andreoli AJ, Ikeda M, Nishizuka Y, Hayaishi O (1963). "Quinolinic acid: a precursor to nicotinamide adenine dinucleotide in Escherichia coli." Biochem Biophys Res Commun 12;92-7. PMID: 14013029

Begley01: Begley TP, Kinsland C, Mehl RA, Osterman A, Dorrestein P (2001). "The biosynthesis of nicotinamide adenine dinucleotides in bacteria." Vitam Horm 61;103-19. PMID: 11153263

Chandler70: Chandler JL, Gholson RK, Scott TA (1970). "Studies on the de novo biosynthesis of NAD in Escherichia coli. I. Labelling patterns from precursors." Biochim Biophys Acta 222(2);523-6. PMID: 4321550

Ortega60: Ortega MV, Brown GM (1960). "Precursors of nicotinic acid in Escherichia coli." J Biol Chem 235;2939-45. PMID: 13731310

Panozzo02: Panozzo C, Nawara M, Suski C, Kucharczyka R, Skoneczny M, Becam AM, Rytka J, Herbert CJ (2002). "Aerobic and anaerobic NAD+ metabolism in Saccharomyces cerevisiae." FEBS Lett 517(1-3);97-102. PMID: 12062417

Rizzi02: Rizzi M, Schindelin H (2002). "Structural biology of enzymes involved in NAD and molybdenum cofactor biosynthesis." Curr Opin Struct Biol 12(6);709-20. PMID: 12504674

Suzuki73: Suzuki N, Carlson J, Griffith G, Gholson RK (1973). "Studies on the de novo biosynthesis of NAD in Escherichia coli. V. Properties of the quinolinic acid synthetase system." Biochim Biophys Acta 304(2);309-15. PMID: 4351074

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Allibert87: Allibert P, Willison JC, Vignais PM (1987). "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 169(1);260-71. PMID: 3025172

Bhatia96: Bhatia R, Calvo KC (1996). "The sequencing expression, purification, and steady-state kinetic analysis of quinolinate phosphoribosyl transferase from Escherichia coli." Arch Biochem Biophys 325(2);270-8. PMID: 8561507

Bork94: Bork P, Koonin EV (1994). "A P-loop-like motif in a widespread ATP pyrophosphatase domain: implications for the evolution of sequence motifs and enzyme activity." Proteins 20(4);347-55. PMID: 7731953

Bossi02: Bossi RT, Negri A, Tedeschi G, Mattevi A (2002). "Structure of FAD-bound L-aspartate oxidase: insight into substrate specificity and catalysis." Biochemistry 41(9);3018-24. PMID: 11863440

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Brown90a: Brown OR, Seither RL (1990). "Paraquat toxicity and pyridine nucleotide coenzyme synthesis: a data correction." Free Radic Biol Med 8(2);113-6. PMID: 2139629

Ceciliani00: Ceciliani F, Caramori T, Ronchi S, Tedeschi G, Mortarino M, Galizzi A (2000). "Cloning, overexpression, and purification of Escherichia coli quinolinate synthetase." Protein Expr Purif 2000;18(1);64-70. PMID: 10648170

Chandler72: Chandler JL, Gholson RK (1972). "De novo biosynthesis of nicotinamide adenine dinucleotide in Escherichia coli: excretion of quinolinic acid by mutants lacking quinolinate phosphoribosyl transferase." J Bacteriol 111(1);98-102. PMID: 4360223

Cicchillo05: Cicchillo RM, Tu L, Stromberg JA, Hoffart LM, Krebs C, Booker SJ (2005). "Escherichia coli quinolinate synthetase does indeed harbor a [4Fe-4S] cluster." J Am Chem Soc 127(20);7310-1. PMID: 15898769

Dahmen67: Dahmen W, Webb B, Preiss J (1967). "The deamido-diphosphopyridine nucleotide and diphosphopyridine nucleotide pyrophosphorylases of Escherichia coli and yeast." Arch Biochem Biophys 1967;120(2);440-50. PMID: 4291828

De09: De Lay N, Gottesman S (2009). "The Crp-activated small noncoding regulatory RNA CyaR (RyeE) links nutritional status to group behavior." J Bacteriol 191(2);461-76. PMID: 18978044

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

DraczynskaLusia92: Draczynska-Lusiak B, Brown OR (1992). "Protein A of quinolinate synthetase is the site of oxygen poisoning of pyridine nucleotide coenzyme synthesis in Escherichia coli." Free Radic Biol Med 13(6);689-93. PMID: 1459486

Flachmann88: Flachmann R, Kunz N, Seifert J, Gutlich M, Wientjes FJ, Laufer A, Gassen HG (1988). "Molecular biology of pyridine nucleotide biosynthesis in Escherichia coli. Cloning and characterization of quinolinate synthesis genes nadA and nadB." Eur J Biochem 1988;175(2);221-8. PMID: 2841129

Gardner90: Gardner PR, Fridovich I (1990). "Quinolinate phosphoribosyl transferase is not the oxygen-sensitive site of nicotinamide adenine dinucleotide biosynthesis." Free Radic Biol Med 8(2);117-9. PMID: 2139630

Gardner91: Gardner PR, Fridovich I (1991). "Quinolinate synthetase: the oxygen-sensitive site of de novo NAD(P)+ biosynthesis." Arch Biochem Biophys 284(1);106-11. PMID: 1846509

Gerdes02: Gerdes SY, Scholle MD, D'Souza M, Bernal A, Baev MV, Farrell M, Kurnasov OV, Daugherty MD, Mseeh F, Polanuyer BM, Campbell JW, Anantha S, Shatalin KY, Chowdhury SA, Fonstein MY, Osterman AL (2002). "From genetic footprinting to antimicrobial drug targets: examples in cofactor biosynthetic pathways." J Bacteriol 184(16);4555-72. PMID: 12142426

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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