The chemistry of the vitamin B3 metabolome

The functional cofactors derived from vitamin B3 are nicotinamide adenine dinucleotide (NAD⁺), its phosphorylated form, nicotinamide adenine dinucleotide phosphate (NADP⁺) and their reduced forms (NAD(P)H). These cofactors, together referred as the NAD(P)(H) pool, are intimately implicated in all essential bioenergetics, anabolic and catabolic pathways in all forms of life. This pool also contributes to post-translational protein modifications and second messenger generation. Since NAD⁺ seats at the cross-road between cell metabolism and cell signaling, manipulation of NAD⁺ bioavailability through vitamin B3 supplementation has become a valuable nutritional and therapeutic avenue. Yet, much remains unexplored regarding vitamin B3 metabolism. The present review highlights the chemical diversity of the vitamin B3-derived anabolites and catabolites of NAD⁺ and offers a chemical perspective on the approaches adopted to identify, modulate and measure the contribution of various precursors to the NAD(P)(H) pool.