Fig. 1: The synthesis and utilization of NAD+ within various cellular compartments, including the cytoplasm, mitochondria, and nucleus.

In the cytoplasm, NAD⁺ is synthesized from precursors such as nicotinamide (NAM), nicotinic acid (NA), and tryptophan (Trp) through distinct metabolic pathways, including the Preiss-Handler pathway, the de novo synthesis pathway, and the salvage pathway—the latter being particularly predominant in mammalian cells. Within the mitochondria, NAD⁺ functions as a coenzyme for various dehydrogenases involved in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation, playing a critical role in mitochondrial function and ATP production. In the nucleus, NAD⁺ serves as a substrate for PARP-mediated ADP-ribosylation and SIRT-mediated deacetylation, both of which are essential for the regulation of chromatin structure and the DNA damage response.