Figure 2.

NAD⁺metabolism connects cellular sub-compartments. Most cellular NAD⁺ is regenerated through the salvage pathway from NAM and to a smaller extent through de novo biosynthesis from dietary sources such as NR (nutrient). The rate-limiting reaction from NAM to NMN is catalyzed by NAMPT enzyme in the nucleocytosol. Three different NMNAT enzymes catalyze the compartmentalized regeneration of NAD⁺ from the same pool of NMN. The NAD⁺/NADH pair has key redox functions in the tricarboxylic acid (TCA) cycle and the electron transport chain to drive ATP generation.