NAD\(^+\)-consuming enzyme

NAD\(^+\)-consuming enzymes are a broad family of proteins that utilize nicotinamide adenine dinucleotide (NAD\(^+\)) as a substrate or cofactor in various cellular processes such as DNA repair, post-translational protein modification, and signaling[1][2][3][5][6][8]. Key families include sirtuins (deacetylases controlling epigenetic and metabolic regulation), poly(ADP-ribose) polymerases (PARPs; involved in DNA repair and cell stress responses), and cyclic ADP-ribose synthases (e.g., CD38, important in immune modulation and calcium signaling)[1][3][5][6][8]. More recently, the neuronal protein SARM1, which cleaves NAD\(^+\) and is involved in axonal degeneration, has been added to this group[6][8]. These enzymes are implicated in aging, cancer, inflammation, metabolic, and neurodegenerative diseases. They are clinically significant as both disease markers and therapeutic targets, notably in oncology and autoimmune indications, with several targeted small molecules and monoclonal antibodies approved or in clinical development[5][8].

Other names

NAD\(^+\)-utilizing enzymeNAD\(^+\) hydrolase familyNAD-dependent enzyme

Enzymatic inhibition (competitive, allosteric, or substrate-based); Blockade of NAD\(^+\) binding site; Modulation of gene expression via epigenetic effects; Disruption of protein-protein interactions