Nicotinamide adenine dinucleotide-dependent enzyme (NAD-dependent enzyme)

Nicotinamide adenine dinucleotide-dependent enzymes are a large and diverse class of enzymes that require NAD+ as a cofactor or substrate. They play central roles in redox reactions (such as those in glycolysis, the TCA cycle, and fatty acid oxidation), DNA repair (notably the poly(ADP-ribose) polymerase, or PARP, family), epigenetic regulation (such as sirtuins), cell signaling (via ADP-ribosyl cyclases), and numerous other core metabolic and signaling processes. Their biological importance makes specific members therapeutic targets for a range of diseases, including cancer, aging-related disorders, neurodegeneration, and metabolic syndrome. Drugs targeting NAD-dependent enzymes include both inhibitors (e.g., PARP inhibitors in cancer therapy) and activators (e.g., sirtuin activators, NAD precursors). Since these enzymes are vital for normal cell function, non-specific modulation can lead to significant toxicity, requiring careful targeting and biomarker monitoring in therapeutic applications[2][3][4][9].

Other names

NAD-dependent enzymeNAD+-dependent enzymeNAD(H)-dependent enzymeNAD-requiring enzymeNAD-utilizing enzyme

Enzyme inhibition (directly inhibit NAD-dependent enzyme, e.g., PARP inhibitors prevent DNA repair in cancer cells); Enzyme activation (compounds that activate sirtuins to promote longevity-associated processes); Substrate competition or depletion (e.g., depleting cellular NAD+ to block enzyme activity)