NAD synthesis pathway enzyme

NAD synthesis pathway enzymes comprise a group of enzymes responsible for the biosynthesis and maintenance of intracellular NAD+ and NADP+ pools, crucial cofactors for cellular redox reactions and metabolic pathways. Major enzymes in mammalian cells include nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide riboside kinase (NRK), nicotinic acid phosphoribosyltransferase (NAPRT), NMN adenylyltransferase (NMNAT), NAD synthetase (NADSYN), and NAD kinase (NADK), each governing key steps in the de novo, Preiss–Handler, or salvage pathways[3][4][8]. These enzymes regulate processes such as glycolysis, oxidative phosphorylation, DNA repair (via substrates for sirtuins and PARPs), and are implicated in circadian rhythm and immune signaling[2][4][10]. Their essentiality to cell viability makes several of them (especially NAMPT and NADK) major targets for cancer, inflammatory, and neurodegenerative diseases[5][6][8]. Multiple drugs and research compounds aim to disrupt NAD synthesis for therapeutic benefit, though balancing efficacy and safety remains challenging due to systemic metabolic requirements.

Other names

NAD biosynthesis enzymeNAD+ synthesis enzymeNAD(P) biosynthesis enzymeNAD pathway enzyme

Inhibition of salvage pathway (e.g., NAMPT inhibitors decrease NAD+ levels, affecting metabolic and DNA repair processes, causing cancer cell death); Inhibition of de novo or Preiss–Handler pathway enzymes, depleting cellular NAD(P) pools and impacting redox metabolism and cell survival; Direct enzyme inhibition (blocking catalytic activity of biosynthesis enzymes); Indirect effects through downstream metabolite depletion