MetaCyc Pathway: pyridine nucleotide cycling (plants)
Inferred from experimentTraceable author statement to experimental support

Pathway diagram: pyridine nucleotide cycling (plants)

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

Superclasses: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisNAD Metabolism

Some taxa known to possess this pathway include : Nicotiana tabacum

Expected Taxonomic Range: Viridiplantae

General Background

The pyridine nucleotide NAD and NADP are ubiquitous coenzymes that may have impact on virtually every metabolic pathway in the cell [Noctor06] [Moat87]. The biosynthesis of NAD in plants is realized via two major routes the de novo synthesis of NAD (see NAD biosynthesis I (from aspartate)) and the pyridine nucleotide cycle (this pathway). The name of the latter was coined to summarize the various routes of degradation and salvage of pyridine compounds [Gholson66]. In dependence on the plant species investigated the pyridine nucleotide cycle may involve a varying number of steps emphasizing the flexibility of this pathway in response to organism-specific and/or environmental conditions [Wagner86a, Zheng04a, Zheng05b, Ashihara05].

The pyridine nucleotide cycling pathway ensures the homeostatic replenishment of NAD when the coenzyme has been involved in NAD consuming reactions. The pathway is fairly similar to the bacterial variant ( NAD salvage pathway I) with the exception that some enzymes, e.g. NMN amidohydrolase, NAD synthase (NH3-dependent) have not been identified in plants, and that plants are capable of by-passing enzymes under certain conditions, hence conferring a broader adaptability [Noctor06].

About This Pathway

The anaplerotic enzyme of the pyridine nucleotide cycle is quinolinic acid phosphoribosyltransferase (QPRtase) ( NAD biosynthesis I (from aspartate)) forming β-nicotinate D-ribonucleotide (nicotinate mononucleotide, NaMN) which may be considered as the start compound of this cycle [Wagner84] [Sinclair00]. From there two different routes can be taken to produce nicotinate, an important intermediate that gives rise to several secondary metabolites, e.g. trigonelline ( trigonelline biosynthesis).

The enzyme catalyzing the direct conversion to nicotinate, i.e. NaMN nucleosidase (synonym NaMN glycohydrolase - NaMN-Ghase) has been partially purified from tobacco. The other route comprises several enzymatic steps that include the formation of the main intermediates nicotinate adenine dinucleotide (NaAD), NAD, nicotinamide mononucleotide (NMN) and nicotinamide. The enzyme that catalyzes the final step of the formation of nicotinate from nicotinamide, i.e. nicotinamidase has been identified in several plants [Wagner86a, Joshi60, Ashihara05, Zheng05b] indicating the main stream of this pathway. The reverse reaction catalyzed by nicotinamide phosphoribosyltransferase (NPRT) has not been detected in plants [Hunt04, Zheng05b]. The final step closing the cycle by converting nicotinate to nicotinate mononucleotide (NaMN) is catalyzed by nicotinic acid phosphoribosyltransferase (Na-PRtase) [Wagner86b, Mann74a]. This enzyme expressed a high affinity towards nicotinate but did not accept nicotinamide as its counterpart enzyme in animals [Wagner86a].

The pathway displays two additional routes that can be taken to form either nicotinamide from NMN or nicotinate mononucleotide (NaMN) from nicotinate. Both form the nucleotide riboside intermediates that are catabolized by 5'-nucleotidase and NMN nucleosidase (via NMN riboside) and nucleoside phosphorylase and nicotinate ribose kinase (via nicotinate riboside), respectively. Some of those activities and the nucleoside ribosides have been found in plants [Noctor06, Hunt04, Zheng05b, Polya75, Eastwell82] but the enzymes remain to be further characterized.

Created 16-Oct-2006 by Foerster H, TAIR


Ashihara05: Ashihara H, Stasolla C, Yin Y, Loukanina N, Thorpe TA (2005). "De novo and salvage biosynthetic pathways of pyridine nucleotides and nicotinic acid conjugates in cultured plant cells." Plant Science, 169, 107-114.

Eastwell82: Eastwell KC, Stumpf PK (1982). "The presence of 5'-nucleotidase in swiss chard chloroplasts." Biochem Biophys Res Commun 108(4);1690-4. PMID: 6295388

Gholson66: Gholson RK (1966). "The pyridine nucleotide cycle." Nature 212(5065);933-5. PMID: 4306794

Hunt04: Hunt L, Lerner F, Ziegler M (2004). "NAD - new roles in signalling and gene regulation in plants." New Phytologist 163, 31-44.

Joshi60: Joshi JG, Handler P (1960). "Biosynthesis of trigonelline." J Biol Chem 235;2981-3. PMID: 13790768

Mann74a: Mann DF, Byerrum RU (1974). "Activation of the de Novo Pathway for Pyridine Nucleotide Biosynthesis Prior to Ricinine Biosynthesis in Castor Beans." Plant Physiol 53(4);603-609. PMID: 16658750

Moat87: Moat AG, Foster JW (1987). "Biosynthesis and salvage pathway of pyridine nucleotides." In: Pyridine nucleotide coenzymes Part B, Chemical, biochemical, and medical aspects. Dolphin D, Avramovic O, Poulson R (eds.), John Wilwy & Sons, New York-Chichester-Brisbane-Toronto-Singapore, 1-24.

Noctor06: Noctor G, Queval G, Gakiere B (2006). "NAD(P) synthesis and pyridine nucleotide cycling in plants and their potential importance in stress conditions." J Exp Bot 57(8);1603-20. PMID: 16714307

Polya75: Polya GM (1975). "Purification and characterization of a cyclic nucleotide-regulated 5'-nucleotidase from potato." Biochimica et Biophysica Acta, 384, 443-457.

Sinclair00: Sinclair SJ, Murphy KJ, Birch CD, Hamill JD (2000). "Molecular characterization of quinolinate phosphoribosyltransferase (QPRtase) in Nicotiana." Plant Mol Biol 44(5);603-17. PMID: 11198422

Wagner84: Wagner R, Wagner KG (1984). "Determination of quinolinic acid phosphoribosyltransferase in tobacco." Phytochemistry, 23(9), 1881-1883.

Wagner86a: Wagner R, Feth F, Wagner KG (1986). "The pyridine-nucleotide cycle in tobacco. Enzyme activities for the recycling of NAD." Planta,167, 226-232.

Wagner86b: Wagner R, Feth F, Wagner KG (1986). "The regulation of enzyme activities of the nicotine pathway in tobacco." Physiol. Plantarum, 68, 667-672.

Zheng04a: Zheng XQ, Nagai C, Ashihara H (2004). "Pyridine nucleotide cycle and trigonelline (N-methylnicotinic acid) synthesis in developing leaves and fruits of Coffea arabica." Physiologia Plantarum, 122, 404-411.

Zheng05b: Zheng XQ, Hayashibe E, Ashihara H (2005). "Changes in trigonelline (N-methylnicotinic acid) content and nicotinic acid metabolism during germination of mungbean (Phaseolus aureus) seeds." J Exp Bot 56(416);1615-23. PMID: 15837705

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

Baecker78: Baecker PA, Yung SG, Rodriguez M, Austin E, Andreoli AJ (1978). "Periplasmic localization of nicotinate phosphoribosyltransferase in Escherichia coli." J Bacteriol 1978;133(3);1108-12. PMID: 346557

Belenky07: Belenky P, Racette FG, Bogan KL, McClure JM, Smith JS, Brenner C (2007). "Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+." Cell 129(3);473-84. PMID: 17482543

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

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

Emanuelli01: Emanuelli M, Carnevali F, Saccucci F, Pierella F, Amici A, Raffaelli N, Magni G (2001). "Molecular cloning, chromosomal localization, tissue mRNA levels, bacterial expression, and enzymatic properties of human NMN adenylyltransferase." J Biol Chem 276(1);406-12. PMID: 11027696

Emanuelli99: Emanuelli M, Carnevali F, Lorenzi M, Raffaelli N, Amici A, Ruggieri S, Magni G (1999). "Identification and characterization of YLR328W, the Saccharomyces cerevisiae structural gene encoding NMN adenylyltransferase. Expression and characterization of the recombinant enzyme." FEBS Lett 455(1-2);13-7. PMID: 10428462

Hara03: Hara N, Yamada K, Terashima M, Osago H, Shimoyama M, Tsuchiya M (2003). "Molecular identification of human glutamine- and ammonia-dependent NAD synthetases. Carbon-nitrogen hydrolase domain confers glutamine dependency." J Biol Chem 278(13);10914-21. PMID: 12547821

Imsande61: Imsande J (1961). "Pathway of diphosphopyridine nucleotide biosynthesis in Escherichia coli." J Biol Chem 1961;236(5):1494-1497. PMID: 13717628

Kahn86: Kahn DW, Anderson BM (1986). "Characterization of Haemophilus influenzae nucleotide pyrophosphatase. An enzyme of critical importance for growth of the organism." J Biol Chem 261(13);6016-25. PMID: 3009442

Kemmer01: Kemmer G, Reilly TJ, Schmidt-Brauns J, Zlotnik GW, Green BA, Fiske MJ, Herbert M, Kraiss A, Schlor S, Smith A, Reidl J (2001). "NadN and e (P4) are essential for utilization of NAD and nicotinamide mononucleotide but not nicotinamide riboside in Haemophilus influenzae." J Bacteriol 183(13);3974-81. PMID: 11395461

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lau09: Lau C, Niere M, Ziegler M (2009). "The NMN/NaMN adenylyltransferase (NMNAT) protein family." Front Biosci (Landmark Ed) 14;410-31. PMID: 19273075

Mehl00: Mehl RA, Kinsland C, Begley TP (2000). "Identification of the Escherichia coli nicotinic acid mononucleotide adenylyltransferase gene." J Bacteriol 2000;182(15);4372-4. PMID: 10894752

Misumi90: Misumi Y, Ogata S, Hirose S, Ikehara Y (1990). "Primary structure of rat liver 5'-nucleotidase deduced from the cDNA. Presence of the COOH-terminal hydrophobic domain for possible post-translational modification by glycophospholipid." J Biol Chem 265(4);2178-83. PMID: 2298743

Natalini86: Natalini P, Ruggieri S, Raffaelli N, Magni G (1986). "Nicotinamide mononucleotide adenylyltransferase. Molecular and enzymatic properties of the homogeneous enzyme from baker's yeast." Biochemistry 25(12);3725-9. PMID: 3013296

Nishiyama91: Nishiyama M, Horinouchi S, Kobayashi M, Nagasawa T, Yamada H, Beppu T (1991). "Cloning and characterization of genes responsible for metabolism of nitrile compounds from Pseudomonas chlororaphis B23." J Bacteriol 173(8);2465-72. PMID: 2013568

Pardee71: Pardee AB, Benz EJ, St Peter DA, Krieger JN, Meuth M, Trieshmann HW (1971). "Hyperproduction and purification of nicotinamide deamidase, a microconstitutive enzyme of Escherichia coli." J Biol Chem 1971;246(22);6792-6. PMID: 4399474

Park88: Park UE, Roth JR, Olivera BM (1988). "Salmonella typhimurium mutants lacking NAD pyrophosphatase." J Bacteriol 170(8);3725-30. PMID: 2841298

Raffaelli02: Raffaelli N, Sorci L, Amici A, Emanuelli M, Mazzola F, Magni G (2002). "Identification of a novel human nicotinamide mononucleotide adenylyltransferase." Biochem Biophys Res Commun 297(4);835-40. PMID: 12359228

Reidl00: Reidl J, Schlor S, Kraiss A, Schmidt-Brauns J, Kemmer G, Soleva E (2000). "NADP and NAD utilization in Haemophilus influenzae." Mol Microbiol 35(6);1573-81. PMID: 10760156

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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