NAD salvage pathway I (Escherichia coli)

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1-19pncCNicotinic acidNicotinamide ribotidenudCNMN nucleosidaseD-Ribose5-phosphatenadDnadENADnucleosidasepncBAdenosinediphosphateriboseNiacinamidepncANADNicotinic acidmononucleotideNicotinic acidadeninedinucleotideHydrogen IonAdenosinemonophosphateAmmoniaWaterL-GlutamineL-Glutamic acidAdenosinetriphosphatePyrophosphatePhosphoribosylpyrophosphateHydrogen IonAdenosinetriphosphatePyrophosphatePyrophosphateHydrogen IonHydrogen IonWaterWaterWaterHydrogen IonHydrogen IonAdenosinemonophosphateHydrogen IonAmmoniaHydrogen IonWaterNiacinamideHydrogen IonWater


Description

Even though NAD molecules are not consumed during oxidation reactions, they have a relatively short half-life. For example, in E. coli the NAD+ half-life is 90 minutes. Once enzymatically degraded, the pyrimidine moiety of the molecule can be recouped via the NAD salvage cycles. This pathway is used for two purposes: it recycles the internally degraded NAD products nicotinamide D-ribonucleotide (also known as nicotinamide mononucleotide, or NMN) and nicotinamide, and it is used for the assimilation of exogenous NAD+.

Since the NAD+ molecule is highly polar, it has to be hydrolyzed before it can be transported across the cytoplasmic membrane for final uptake. It does seem to be able to penetrate the external membrane, though, as the enzymes that break it down are found in the periplasm [Park88]. NAD+ is first hydrolyzed by NAD pyrophosphatase into NMN , which can be hydrolyzed further to nicotinamide by NMN nucleosidase. Both enzymes are periplasmic. Both NMN and nicotinamide can be transported across the inner membrane into the cytoplasm. Once there, nicotinamide is converted via nicotinate to nicotinate nucleotide, at which point the pathway merges with the de novo biosynthesis pathway, and continues to NAD via deamido-NAD.

There are several flavors of the salvage pathway found in different organisms, and even within the same organism. The one described above contains 6 reaction steps, and is often referred to as the PNC VI pathway, for Pyridine Nucleotide Cycling. However, there are also a four-step cycle and a five-step cycle, termed PNC IV and V, respectively [Foster79, Foster80]. In the PNC IV cycle, the enzyme NMN amidohydrolase (also called NMN deamidase) converts NMN (which can be transported across the inner membrane in Enterobacteria) directly to nicotinate nucleotide, bypassing the enzymes nicotinamidase (PncA) and nicotine phosphoribosyl transferase (PncB), which are members of the PNC VI cycle. PNC IV is the major intracellular recycling pathway in E. coli [Hillyard81], while PNC VI is the major cycle of Salmonella typhimurium [Foster80].

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source: http://biocyc.org/ECOLI/NEW-IMAGE?type=PATHWAY&object=PYRIDNUCSAL-PWY&detail-level=2

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Bibliography

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  1. Bork P, Koonin EV; ''A P-loop-like motif in a widespread ATP pyrophosphatase domain: implications for the evolution of sequence motifs and enzyme activity.''; Proteins, 1994 PubMed Europe PMC
  2. Baecker PA, Yung SG, Rodriguez M, Austin E, Andreoli AJ; ''Periplasmic localization of nicotinate phosphoribosyltransferase in Escherichia coli.''; J Bacteriol, 1978 PubMed Europe PMC
  3. 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; ''From genetic footprinting to antimicrobial drug targets: examples in cofactor biosynthetic pathways.''; J Bacteriol, 2002 PubMed Europe PMC
  4. Ozment C, Barchue J, DeLucas LJ, Chattopadhyay D; ''Structural study of Escherichia coli NAD synthetase: overexpression, purification, crystallization, and preliminary crystallographic analysis.''; J Struct Biol, 1999 PubMed Europe PMC
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  6. Jauch R, Humm A, Huber R, Wahl MC; ''Structures of Escherichia coli NAD synthetase with substrates and products reveal mechanistic rearrangements.''; J Biol Chem, 2005 PubMed Europe PMC
  7. Foster JW, Baskowsky-Foster AM; ''Pyridine nucleotide cycle of Salmonella typhimurium: in vivo recycling of nicotinamide adenine dinucleotide.''; J Bacteriol, 1980 PubMed Europe PMC
  8. De Lay N, Gottesman S; ''The Crp-activated small noncoding regulatory RNA CyaR (RyeE) links nutritional status to group behavior.''; J Bacteriol, 2009 PubMed Europe PMC
  9. Galeazzi L, Bocci P, Amici A, Brunetti L, Ruggieri S, Romine M, Reed S, Osterman AL, Rodionov DA, Sorci L, Raffaelli N; ''Identification of nicotinamide mononucleotide deamidase of the bacterial pyridine nucleotide cycle reveals a novel broadly conserved amidohydrolase family.''; J Biol Chem, 2011 PubMed Europe PMC
  10. Mehl RA, Kinsland C, Begley TP; ''Identification of the Escherichia coli nicotinic acid mononucleotide adenylyltransferase gene.''; J Bacteriol, 2000 PubMed Europe PMC
  11. Hillyard D, Rechsteiner M, Manlapaz-Ramos P, Imperial JS, Cruz LJ, Olivera BM; ''The pyridine nucleotide cycle. Studies in Escherichia coli and the human cell line D98/AH2.''; J Biol Chem, 1981 PubMed Europe PMC
  12. Isaksson LA, Takata R; ''The temperature sensitive mutant 72c. I. Pleiotropic growth behaviour and changed response to some antibiotics and mutations in the transcription or translation apparatus.''; Mol Gen Genet, 1978 PubMed Europe PMC
  13. Park UE, Roth JR, Olivera BM; ''Salmonella typhimurium mutants lacking NAD pyrophosphatase.''; J Bacteriol, 1988 PubMed Europe PMC
  14. Dahmen W, Webb B, Preiss J; ''The deamido-diphosphopyridine nucleotide and diphosphopyridine nucleotide pyrophosphorylases of Escherichia coli and yeast.''; Arch Biochem Biophys, 1967 PubMed Europe PMC
  15. Khil PP, Camerini-Otero RD; ''Over 1000 genes are involved in the DNA damage response of Escherichia coli.''; Mol Microbiol, 2002 PubMed Europe PMC
  16. 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 PubMed Europe PMC
  17. IMSANDE J; ''Pathway of diphosphopyridine nucleotide biosynthesis in Escherichia coli.''; J Biol Chem, 1961 PubMed Europe PMC
  18. Pardee AB, Benz EJ Jr, St Peter DA, Krieger JN, Meuth M, Trieshmann HW Jr; ''Hyperproduction and purification of nicotinamide deamidase, a microconstitutive enzyme of Escherichia coli.''; J Biol Chem, 1971 PubMed Europe PMC
  19. Foster JW, Kinney DM, Moat AG; ''Pyridine nucleotide cycle of Salmonella typhimurium: isolation and characterization of pncA, pncB, and pncC mutants and utilization of exogenous nicotinamide adenine dinucleotide.''; J Bacteriol, 1979 PubMed Europe PMC

History

View all...
CompareRevisionActionTimeUserComment
106099view12:00, 16 August 2019MaintBotHMDB identifier normalization
71962view23:35, 23 October 2013MaintBotAutomated update of data sources
62865view10:30, 3 May 2013CizarModified description
62262view22:15, 26 April 2013AlexanderPicoModified description
62261view22:15, 26 April 2013AlexanderPicoOntology Term : 'pyridine nucleotide biosynthetic pathway' added !
62260view21:58, 26 April 2013AlexanderPicoOntology Term : 'NAD biosynthetic pathway' added !
62259view21:58, 26 April 2013AlexanderPicoOntology Term : 'purine salvage pathway' added !
62258view21:58, 26 April 2013AlexanderPicoOntology Term : 'PW:0000863' removed !
62251view21:50, 26 April 2013AlexanderPicoModified categories
62250view21:50, 26 April 2013AlexanderPicoOntology Term : 'pyrimidine salvage pathway' added !
62003view09:16, 23 April 2013CizarSpecify description
62002view09:15, 23 April 2013CizarCorrected and added some annotations
61952view07:36, 22 April 2013Cizargrouped metabolites and aligned them
61803view10:47, 19 April 2013CizarModified description
61802view10:31, 19 April 2013Cizaraddded references
61795view09:51, 19 April 2013CizarNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
Adenosine

diphosphate

ribose
MetaboliteHMDB0001178 (HMDB)
Adenosine monophosphateMetaboliteHMDB0000045 (HMDB)
Adenosine triphosphateMetaboliteHMDB0000538 (HMDB)
AmmoniaMetaboliteHMDB0000051 (HMDB)
D-Ribose 5-phosphateMetaboliteHMDB0001548 (HMDB)
Hydrogen IonMetaboliteHMDB0059597 (HMDB)
L-Glutamic acidMetaboliteHMDB0000148 (HMDB)
L-GlutamineMetaboliteHMDB0000641 (HMDB)
NAD nucleosidaseGeneProduct
NADMetaboliteHMDB0000902 (HMDB)
NMN nucleosidaseGeneProduct
NiacinamideMetaboliteHMDB0001406 (HMDB)
Nicotinamide ribotideMetaboliteHMDB0000229 (HMDB)
Nicotinic acid

adenine

dinucleotide
MetaboliteHMDB0001179 (HMDB)
Nicotinic acid mononucleotideMetaboliteHMDB0001132 (HMDB)
Nicotinic acidMetaboliteHMDB0001488 (HMDB)
Phosphoribosyl pyrophosphateMetaboliteHMDB0000280 (HMDB)
PyrophosphateMetaboliteHMDB0000250 (HMDB)
WaterMetaboliteHMDB0002111 (HMDB)
nadDGeneProductEBESCG00000001808 (Ensembl)
nadEGeneProductEBESCG00000001347 (Ensembl)
nudCGeneProductEBESCG00000003522 (Ensembl)
pncAGeneProductEBESCG00000002953 (Ensembl)
pncBGeneProductEBESCG00000000193 (Ensembl)
pncCGeneProduct

Annotated Interactions

No annotated interactions
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