Despite the presence of the de novo pathway, the salvage reactions are essential in humans; a lack of niacin in the diet causes the vitamin deficiency disease pellagra. This high requirement for NAD results from the constant consumption of the coenzyme in reactions such as posttranslational modifications, since the cycling of NAD between oxidized and reduced forms in redox reactions does not change the overall levels of the coenzyme.
The major source of NAD in mammals is the salvage pathway which recycles the nicotinamide produced by enzymes utilizing NAD. The first step, and the rate-limiting enzyme in the salvage pathway is nicotinamide phosphoribosyltransferase (NAMPT), which produces nicotinamide mononucleotide (NMN). NMN is the immediate precursor to NAD+ in the salvage pathway.
Besides assembling NAD de novo from simple amino acid precursors, cells also salvage preformed compounds containing a pyridine base. The three vitamin precursors used in these salvage metabolic pathways are nicotinic acid (NA), nicotinamide (Nam) and nicotinamide riboside (NR). These compounds can be taken up from the diet and are termed vitamin B or niacin. However, these compounds are also produced within cells and by digestion of cellular NAD. Some of the enzymes involved in these salvage pathways appear to be concentrated in the cell nucleus, which may compensate for the high level of reactions that consume NAD in this organelle. There are some reports that mammalian cells can take up extracellular NAD from their surroundings, and both nicotinamide and nicotinamide riboside can be absorbed from the gut.
The salvage pathways used in microorganisms differ from those of mammals. Some pathogens, such as the yeast Candida glabrata and the bacterium Haemophilus influenzae are NAD auxotrophs – they cannot synthesize NAD – but possess salvage pathways and thus are dependent on external sources of NAD or its precursors. Even more surprising is the intracellular pathogen Chlamydia trachomatis, which lacks recognizable candidates for any genes involved in the biosynthesis or salvage of both NAD and NADP, and must acquire these coenzymes from its host.