NAD salvage pathway I (WP2486)

Escherichia coli

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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].

Authors

Cizar and Alex Pico

Activity

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Organisms

Escherichia coli

Communities

Annotations

Pathway Ontology

pyridine nucleotide biosynthetic pathway nicotinamide adenine dinucleotide biosynthetic pathway purine salvage pathway

Participants

Label Type Compact URI Comment
Niacinamide Metabolite hmdb:HMDB0001406
Adenosinediphosphateribose Metabolite hmdb:HMDB0001178
Nicotinic acid Metabolite hmdb:HMDB0001488
Nicotinamide ribotide Metabolite hmdb:HMDB0000229
D-Ribose5-phosphate Metabolite hmdb:HMDB0001548
NAD Metabolite hmdb:HMDB0000902
Nicotinic acidmononucleotide Metabolite hmdb:HMDB0001132
Nicotinic acidadeninedinucleotide Metabolite hmdb:HMDB0001179
Hydrogen Ion Metabolite hmdb:HMDB0059597
Adenosinemonophosphate Metabolite hmdb:HMDB0000045
Ammonia Metabolite hmdb:HMDB0000051
Water Metabolite hmdb:HMDB0002111
L-Glutamine Metabolite hmdb:HMDB0000641
L-Glutamic acid Metabolite hmdb:HMDB0000148
Adenosinetriphosphate Metabolite hmdb:HMDB0000538
Pyrophosphate Metabolite hmdb:HMDB0000250
Phosphoribosylpyrophosphate Metabolite hmdb:HMDB0000280
nadE GeneProduct ensembl:EBESCG00000001347
pncA GeneProduct ensembl:EBESCG00000002953
pncB GeneProduct ensembl:EBESCG00000000193
nudC GeneProduct ensembl:EBESCG00000003522
nadD GeneProduct ensembl:EBESCG00000001808

References

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  2. Periplasmic localization of nicotinate phosphoribosyltransferase in Escherichia coli. Baecker PA, Yung SG, Rodriguez M, Austin E, Andreoli AJ. J Bacteriol. 1978 Mar;133(3):1108–12. PubMed Europe PMC Scholia
  3. The temperature sensitive mutant 72c. I. Pleiotropic growth behaviour and changed response to some antibiotics and mutations in the transcription or translation apparatus. Isaksson LA, Takata R. Mol Gen Genet. 1978 Apr 25;161(1):9–14. PubMed Europe PMC Scholia
  4. Salmonella typhimurium mutants lacking NAD pyrophosphatase. Park UE, Roth JR, Olivera BM. J Bacteriol. 1988 Aug;170(8):3725–30. PubMed Europe PMC Scholia
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