NAD salvage pathway I (Escherichia coli)
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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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diphosphate
riboseadenine
dinucleotideAnnotated Interactions
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