FIGURE 1.

NAD⁺ in S. cerevisiae is synthesized from NA via the salvage pathway and from tryptophan through the de novo pathway. NA and tryptophan imported from the growth medium serve as precursors of NAD⁺. A gray box indicates the activity of sirtuins (Sir2p and Hst1p-4p), NAD⁺-dependent protein deacetylases, which hydrolyze NAD⁺ into nicotinamide and ADP-ribose, in a reaction coupled with protein/histone deacetylation. The enzymes involved in the salvage pathway for NAD⁺ synthesis are primarily localized in the nucleus (52, 62), whereas the enzymes in the de novo pathway are distributed in the nucleus and cytoplasm (52). The de novo pathway converts tryptophan to nicotinic acid mononucleotide in a series of reactions catalyzed by Bna1p–6p. Nicotinic acid mononucleotide is the point of convergence for the de novo and salvage pathways for NAD⁺ biosynthesis. Abbreviations used are as follows: NAD⁺, nicotinamide adenine dinucleotide; NA, nicotinic acid; NAM, nicotinamide; NaMN, nicotinic acid mononucleotide; NaAD, deamido-NAD.