This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → NAD Metabolism|
Some taxa known to possess this pathway include : Escherichia coli K-12 substr. MG1655
The pyridine nucleotide coenzymes nicotinamide adenine dinucleotide (NAD, formerly named DPN) and nicotinamide adenine dinucleotide phosphate (NADP, formerly named TPN) play key roles as cofactors in oxidation-reduction reactions in all living cells. The nicotinamide ring functions as a prosthetic group for these reactions. Their oxidized forms are depicted here as NAD+ and NADP+ due to the positive charge on the nitrogen atom in the nicotinamide ring. Their reduced forms are referred to as NADH and NADPH. Although they appear chemically equivalent, their metabolic roles differ. NAD+ is generally the cofactor for energy-producing oxidation reactions, while NADPH is the cofactor for reductive biosynthetic reactions. The pentose phosphate pathway, the isocitrate dehydrogenase enzyme (Icd) and the PntAB transhydrogenase (see below) are important sources of NADPH (in [Sauer04a]).
Despite their importance, the regulation of NAD+ phosphorylation and dephosphorylation remains incompletely defined in Escherichia coli. Earlier work on the kinetics of pyridine nucleotide metabolism in Escherichia coli demonstrated that the ratio of NADP+ to NAD+ results largely from the rates of NADP+ and NAD+ interconversion (in [Lundquist73]).
The reversible reduction of both NAD+ and NADP+ is carried out by the two transhydrogenase isoforms shown in the reaction links. The PntAB product of genes pntA and pntB is located in the inner membrane and also functions as a proton pump. Its physiological function is to catalyze energy-dependent reduction of NADP+ with NADH. The soluble product of gene sthA is thought to function mainly in the reoxidation of NADPH with NAD+. The expression of these two isoforms is modulated by the redox state of cellular metabolism [Sauer04a]. In [Lundquist71] and reviewed by Penfound, T. and J.W. Foster in [Neidhardt96] (see below).
About This Pathway
NAD kinases have been characterized in organisms from a variety of taxonomic groups including archaea, eubacteria and eukaryotes (reviewed in [Kawai08]). The NAD kinase of Salmonella enterica has been shown to be essential for growth [Grose06] and evidence for its essentiality in Escherichia coli has been presented [Gerdes02].
In contrast, NADP phosphatases (NADPases) remain poorly characterized despite their important role. Although an NAD kinase homolog in the archaeon Methanocaldococcus jannaschii was shown to also have NADP phosphatase activity, NADP phosphatases from eubacterial and eukaryotic sources still require identification of the genes encoding them and further study of their enzymatic properties. In Escherichia coli the product of cysQ showed high NADP and NADPH phosphatase activities, but kinetic studies of the purified enzyme suggested that it is not the true NADP phosphatase of this organism. Reviewed in [Kawai08, Pollak07].
Reviewed in Penfound, T. and J.W. Foster (1996) "Biosynthesis and Recycling of NAD", chapter 48, pp. 721-730, in [Neidhardt96].
Unification Links: EcoCyc:NADPHOS-DEPHOS-PWY
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
Kawai08: Kawai S, Murata K (2008). "Structure and function of NAD kinase and NADP phosphatase: key enzymes that regulate the intracellular balance of NAD(H) and NADP(H)." Biosci Biotechnol Biochem 72(4);919-30. PMID: 18391451
Neidhardt96: Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low Jr KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE "Escherichia coli and Salmonella, Cellular and Molecular Biology, Second Edition." American Society for Microbiology, Washington, D.C., 1996.
Sauer04a: Sauer U, Canonaco F, Heri S, Perrenoud A, Fischer E (2004). "The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of Escherichia coli." J Biol Chem 279(8);6613-9. PMID: 14660605
Ahmad92: Ahmad S, Glavas NA, Bragg PD (1992). "A mutation at Gly314 of the beta subunit of the Escherichia coli pyridine nucleotide transhydrogenase abolishes activity and affects the NADP(H)-induced conformational change." Eur J Biochem 1992;207(2);733-9. PMID: 1633824
Ahmad92a: Ahmad S, Glavas NA, Bragg PD (1992). "Subunit interactions involved in the assembly of pyridine nucleotide transhydrogenase in the membranes of Escherichia coli." J Biol Chem 1992;267(10);7007-12. PMID: 1551908
Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554
Bergkvist00: Bergkvist A, Johansson C, Johansson T, Rydstrom J, Karlsson BG (2000). "Interactions of the NADP(H)-binding domain III of proton-translocating transhydrogenase from escherichia coli with NADP(H) and the NAD(H)-binding domain I studied by NMR and site-directed mutagenesis." Biochemistry 39(41);12595-605. PMID: 11027139
Bieganowski06: Bieganowski P, Seidle HF, Wojcik M, Brenner C (2006). "Synthetic lethal and biochemical analyses of NAD and NADH kinases in Saccharomyces cerevisiae establish separation of cellular functions." J Biol Chem 281(32);22439-45. PMID: 16760478
Bizouarn00: Bizouarn T, Fjellstrom O, Meuller J, Axelsson M, Bergkvist A, Johansson C, Goran Karlsson B, Rydstrom J (2000). "Proton translocating nicotinamide nucleotide transhydrogenase from E. coli. Mechanism of action deduced from its structural and catalytic properties." Biochim Biophys Acta 1457(3);211-28. PMID: 10773166
Bizouarn02: Bizouarn T, Althage M, Pedersen A, Tigerstrom A, Karlsson J, Johansson C, Rydstrom J (2002). "The organization of the membrane domain and its interaction with the NADP(H)-binding site in proton-translocating transhydrogenase from E. coli." Biochim Biophys Acta 1555(1-3);122-7. PMID: 12206903
Bizouarn05: Bizouarn T, van Boxel GI, Bhakta T, Jackson JB (2005). "Nucleotide binding affinities of the intact proton-translocating transhydrogenase from Escherichia coli." Biochim Biophys Acta 1708(3);404-10. PMID: 15935988
Bragg00: Bragg PD, Hou C (2000). "Crosslinking between alpha and beta subunits defines the orientation and spatial relationship of some of the transmembrane helices of the proton-translocating pyridine nucleotide transhydrogenase of Escherichia coli." Biochem Biophys Res Commun 273(3);955-9. PMID: 10891354
Bragg99: Bragg PD, Hou C (1999). "Effect of NBD chloride (4-chloro-7-nitrobenzo-2-oxa-1,3-diazole) on the pyridine nucleotide transhydrogenase of Escherichia coli." Biochim Biophys Acta 1999;1413(3);159-71. PMID: 10556628
Canonaco01: Canonaco F, Hess TA, Heri S, Wang T, Szyperski T, Sauer U (2001). "Metabolic flux response to phosphoglucose isomerase knock-out in Escherichia coli and impact of overexpression of the soluble transhydrogenase UdhA." FEMS Microbiol Lett 204(2);247-52. PMID: 11731130
Clarke85: Clarke DM, Bragg PD (1985). "Purification and properties of reconstitutively active nicotinamide nucleotide transhydrogenase of Escherichia coli." Eur J Biochem 1985;149(3);517-23. PMID: 3891338
Clarke86: Clarke DM, Loo TW, Gillam S, Bragg PD (1986). "Nucleotide sequence of the pntA and pntB genes encoding the pyridine nucleotide transhydrogenase of Escherichia coli." Eur J Biochem 158(3);647-53. PMID: 3525165
Cotton01: Cotton NP, White SA, Peake SJ, McSweeney S, Jackson JB (2001). "The crystal structure of an asymmetric complex of the two nucleotide binding components of proton-translocating transhydrogenase." Structure 9(2);165-76. PMID: 11250201
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
Egorov04: Egorov MV, Tigerstrom A, Pestov NB, Korneenko TV, Kostina MB, Shakhparonov MI, Rydstrom J (2004). "Purification of a recombinant membrane protein tagged with a calmodulin-binding domain: properties of chimeras of the Escherichia coli nicotinamide nucleotide transhydrogenase and the C-terminus of human plasma membrane Ca2+ -ATPase." Protein Expr Purif 36(1);31-9. PMID: 15177281
Showing only 20 references. To show more, press the button "Show all references".
©2016 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493