Escherichia coli K-12 substr. MG1655 Pathway: nitrate reduction VIII (dissimilatory)
Inferred from experiment

Pathway diagram: nitrate reduction VIII (dissimilatory)

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

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for nitrate reduction VIII (dissimilatory)

Synonyms: NADH to nitrate electron transfer

Superclasses: Degradation/Utilization/AssimilationInorganic Nutrients MetabolismNitrogen Compounds MetabolismNitrate Reduction
Generation of Precursor Metabolites and EnergyElectron Transfer
Generation of Precursor Metabolites and EnergyRespirationAnaerobic Respiration

In the anaerobic respiratory chain formed by NADH dehydrogenase and nitrate reductase the transfer of electrons from NADH to nitrate is coupled to the generation of a proton-motive force (H+/e- = 3) across the cytoplasmic membrane ( [Cole68, Garland75, Haddock75] and see [Unden97]).

E. coli K-12 contains two NADH dehydrogenases - energy conserving NDH-I (shown in this pathway) and NDH-II which does not contribute to the proton gradient; both enzymes appear to be involved in anaerobic nitrate respiration [Bongaerts95, Tran97]. By analogy to the related enzyme from mitochondria, NDH-I is thought to function as a proton pump translocating 4H+ per NADH oxidised (2e-) [H+/e- = 2] however a lower ratio of 3H+/2e- has also been proposed [Bogachev96, Wikstrom12]. Nitrate induces the expression of the nuo operon (encoding NDH-I) in a NarL dependent manner [Bongaerts95]

E. coli K-12 also contains two energy conserving (H+/e- = 1) nitrate reductases. Expression of nitrate reductase A (NRA) occurs in response to high levels of nitrate in the environment whereas expression of nitrate reductase Z (NRZ) is not dependent on nitrate levels or anaerobiosis ( [Wang99a] and see [Bonnefoy94]).

Quinones are the obligate redox carriers during anaerobic nitrate respiration; the concentration of menaquinone increases in cells grown anaerobically with nitrate while the concentration of ubiquinone decreases (as compared with cells grown aerobically) [Wallace77]. Nitrate reductase A can use both menaquinol (shown in this pathway) and ubiquinol as electron donors [Wissenbach90, Wissenbach92]. In anaerobic growth with nitrate the major quinone is demethylmenaquinone (DMK) [Unden88]; an E. coli strain containing only demethylmenaquinone is unable to grow with nitrate as terminal reductase [Wissenbach92].

Variants: nitrate reduction III (dissimilatory), nitrate reduction VIIIb (dissimilatory), nitrate reduction IX (dissimilatory), nitrate reduction X (periplasmic, dissimilatory)

Created 17-Aug-2008 by Nolan L, Macquarie University
Revised 11-Dec-2014 by Mackie A, Macquarie University
Last-Curated 11-Dec-2014 by Mackie A, Macquarie University


Bogachev96: Bogachev AV, Murtazina RA, Skulachev VP (1996). "H+/e- stoichiometry for NADH dehydrogenase I and dimethyl sulfoxide reductase in anaerobically grown Escherichia coli cells." J Bacteriol 178(21);6233-7. PMID: 8892824

Bongaerts95: Bongaerts J, Zoske S, Weidner U, Unden G (1995). "Transcriptional regulation of the proton translocating NADH dehydrogenase genes (nuoA-N) of Escherichia coli by electron acceptors, electron donors and gene regulators." Mol Microbiol 16(3);521-34. PMID: 7565112

Bonnefoy94: Bonnefoy V, Demoss JA (1994). "Nitrate reductases in Escherichia coli." Antonie Van Leeuwenhoek 1994;66(1-3);47-56. PMID: 7747940

Cole68: Cole JA, Wimpenny JW (1968). "Metabolic pathways for nitrate reduction in Escherichia coli." Biochim Biophys Acta 162(1);39-48. PMID: 4385809

Garland75: Garland PB, Downie JA, Haddock BA (1975). "Proton translocation and the respiratory nitrate reductase of Escherichia coli." Biochem J 152(3);547-59. PMID: 5996

Haddock75: Haddock BA, Kendall-Tobias MW (1975). "Functional anaerobic electron transport linked to the reduction of nitrate and fumarate in membranes from Escherichia coli as demonstrated by quenching of atebrin fluorescence." Biochem J 152(3);655-9. PMID: 776172

Tran97: Tran QH, Bongaerts J, Vlad D, Unden G (1997). "Requirement for the proton-pumping NADH dehydrogenase I of Escherichia coli in respiration of NADH to fumarate and its bioenergetic implications." Eur J Biochem 244(1);155-60. PMID: 9063459

Unden88: Unden G (1988). "Differential roles for menaquinone and demethylmenaquinone in anaerobic electron transport of E. coli and their fnr-independent expression." Arch Microbiol 150(5);499-503. PMID: 2849923

Unden97: Unden G, Bongaerts J (1997). "Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptors." Biochim Biophys Acta 1320(3);217-34. PMID: 9230919

Wallace77: Wallace BJ, Young IG (1977). "Role of quinones in electron transport to oxygen and nitrate in Escherichia coli. Studies with a ubiA- menA- double quinone mutant." Biochim Biophys Acta 461(1);84-100. PMID: 195602

Wang99a: Wang H, Tseng CP, Gunsalus RP (1999). "The napF and narG nitrate reductase operons in Escherichia coli are differentially expressed in response to submicromolar concentrations of nitrate but not nitrite." J Bacteriol 181(17);5303-8. PMID: 10464201

Wikstrom12: Wikstrom M, Hummer G (2012). "Stoichiometry of proton translocation by respiratory complex I and its mechanistic implications." Proc Natl Acad Sci U S A 109(12);4431-6. PMID: 22392981

Wissenbach90: Wissenbach U, Kroger A, Unden G (1990). "The specific functions of menaquinone and demethylmenaquinone in anaerobic respiration with fumarate, dimethylsulfoxide, trimethylamine N-oxide and nitrate by Escherichia coli." Arch Microbiol 154(1);60-6. PMID: 2204318

Wissenbach92: Wissenbach U, Ternes D, Unden G (1992). "An Escherichia coli mutant containing only demethylmenaquinone, but no menaquinone: effects on fumarate, dimethylsulfoxide, trimethylamine N-oxide and nitrate respiration." Arch Microbiol 1992;158(1);68-73. PMID: 1444716

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

Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

Allison11: Allison KR, Brynildsen MP, Collins JJ (2011). "Metabolite-enabled eradication of bacterial persisters by aminoglycosides." Nature 473(7346);216-20. PMID: 21562562

Amarneh03: Amarneh B, Vik SB (2003). "Mutagenesis of subunit N of the Escherichia coli complex I. Identification of the initiation codon and the sensitivity of mutants to decylubiquinone." Biochemistry 42(17);4800-8. PMID: 12718520

Amarneh10: Amarneh B, Vik SB (2010). "Transmembrane topology of subunit N of complex I (NADH:ubiquinone oxidoreductase) from Escherichia coli." J Bioenerg Biomembr 42(6);511-6. PMID: 21120593

AriasCartin10: Arias-Cartin R, Lyubenova S, Ceccaldi P, Prisner T, Magalon A, Guigliarelli B, Grimaldi S (2010). "HYSCORE evidence that endogenous mena- and ubisemiquinone bind at the same Q site (Q(D)) of Escherichia coli nitrate reductase A." J Am Chem Soc 132(17);5942-3. PMID: 20387886

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Augier93: Augier V, Asso M, Guigliarelli B, More C, Bertrand P, Santini CL, Blasco F, Chippaux M, Giordano G (1993). "Removal of the high-potential [4Fe-4S] center of the beta-subunit from Escherichia coli nitrate reductase. Physiological, biochemical, and EPR characterization of site-directed mutated enzymes." Biochemistry 32(19);5099-108. PMID: 8388253

Augier93a: Augier V, Guigliarelli B, Asso M, Bertrand P, Frixon C, Giordano G, Chippaux M, Blasco F (1993). "Site-directed mutagenesis of conserved cysteine residues within the beta subunit of Escherichia coli nitrate reductase. Physiological, biochemical, and EPR characterization of the mutated enzymes." Biochemistry 32(8);2013-23. PMID: 8383531

Auriol11: Auriol C, Bestel-Corre G, Claude JB, Soucaille P, Meynial-Salles I (2011). "Stress-induced evolution of Escherichia coli points to original concepts in respiratory cofactor selectivity." Proc Natl Acad Sci U S A 108(4);1278-83. PMID: 21205901

Avazeri97: Avazeri C, Turner RJ, Pommier J, Weiner JH, Giordano G, Vermeglio A (1997). "Tellurite reductase activity of nitrate reductase is responsible for the basal resistance of Escherichia coli to tellurite." Microbiology 143 ( Pt 4);1181-9. PMID: 9141681

Banci05: Banci L, Bertini I, Ciofi-Baffoni S, Chasapis CT, Hadjiliadis N, Rosato A (2005). "An NMR study of the interaction between the human copper(I) chaperone and the second and fifth metal-binding domains of the Menkes protein." FEBS J 272(3);865-71. PMID: 15670166

Baranova07: Baranova EA, Holt PJ, Sazanov LA (2007). "Projection structure of the membrane domain of Escherichia coli respiratory complex I at 8 A resolution." J Mol Biol 366(1);140-54. PMID: 17157874

Baranova07a: Baranova EA, Morgan DJ, Sazanov LA (2007). "Single particle analysis confirms distal location of subunits NuoL and NuoM in Escherichia coli complex I." J Struct Biol 159(2);238-42. PMID: 17360196

Belevich07: Belevich G, Euro L, Wikstrom M, Verkhovskaya M (2007). "Role of the conserved arginine 274 and histidine 224 and 228 residues in the NuoCD subunit of complex I from Escherichia coli." Biochemistry 46(2);526-33. PMID: 17209562

Belevich11: Belevich G, Knuuti J, Verkhovsky MI, Wikstrom M, Verkhovskaya M (2011). "Probing the mechanistic role of the long α-helix in subunit L of respiratory Complex I from Escherichia coli by site-directed mutagenesis." Mol Microbiol 82(5);1086-95. PMID: 22060017

Belevich14: Belevich N, Belevich G, Verkhovskaya M (2014). "Real-time optical studies of respiratory Complex I turnover." Biochim Biophys Acta 1837(12);1973-1980. PMID: 25283488

Berks95: Berks BC, Ferguson SJ, Moir JW, Richardson DJ (1995). "Enzymes and associated electron transport systems that catalyse the respiratory reduction of nitrogen oxides and oxyanions." Biochim Biophys Acta 1232(3);97-173. PMID: 8534676

Berks95a: Berks BC, Page MD, Richardson DJ, Reilly A, Cavill A, Outen F, Ferguson SJ (1995). "Sequence analysis of subunits of the membrane-bound nitrate reductase from a denitrifying bacterium: the integral membrane subunit provides a prototype for the dihaem electron-carrying arm of a redox loop." Mol Microbiol 15(2);319-31. PMID: 7746153

Berrisford08: Berrisford JM, Thompson CJ, Sazanov LA (2008). "Chemical and NADH-induced, ROS-dependent, cross-linking between subunits of complex I from Escherichia coli and Thermus thermophilus." Biochemistry 47(39);10262-70. PMID: 18771280

Bertero03: Bertero MG, Rothery RA, Palak M, Hou C, Lim D, Blasco F, Weiner JH, Strynadka NC (2003). "Insights into the respiratory electron transfer pathway from the structure of nitrate reductase A." Nat Struct Biol 10(9);681-7. PMID: 12910261

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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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