FIGURE 4.

NAD⁺ consumption and redox cycling in the heart. SIRT mediates NAD⁺ consumption during deacetylation, where the acetyl group is removed from the acetylated protein (blue). DNA damage activates PARP-mediated NAD⁺ consumption during PARylation, where the ADP-ribose chain is added onto the target proteins (green). CD38-mediates NAD⁺ consumption through cyclization or base-exchange reaction, where two important Ca²⁺-mobilizing second messengers, cADPR or NAADP, are produced from NAD⁺, respectively (orange). CD38 also generates ADPR from NAD⁺ through its glycohydrolase activity. NAM is generated as a byproduct from NAD⁺ consumption. The dash lines indicate recycling of NAM back into NAD⁺ salvage pathway. The redox cycling between NAD⁺ and NADH is indicated in gray.