Nicotinamide adenine dinucleotide kinase (NADK)

Nicotinamide adenine dinucleotide kinase (NADK) is the sole enzyme responsible for phosphorylating NAD+ to generate NADP+, a critical coenzyme required for anabolic metabolism, antioxidant defense, and overall cellular redox balance[1][3]. Human NADK exists as cytosolic and mitochondrial isoforms (NADK and NADK2, respectively), each independently regulating compartmental NADP(H) pools[2][4]. NADK is conserved across all domains of life, with a structurally characterized active site that selectively binds NAD+ and ATP (or other nucleoside triphosphates as phosphate donors in some species) to catalyze the transfer of the 2'-phosphate[1][3]. Regulation of NADK involves both enzymatic cooperativity (in cytosolic isoforms) and post-translational modifications (e.g., Akt-mediated phosphorylation)[2][4]. Functional deficiency of NADK, especially mitochondrial NADK2, leads to severe developmental and neurological defects, highlighting its essential role[2]. NADK is being explored as a therapeutic target in diseases related to oxidative stress, but direct pharmacological modulators have not yet reached clinical application[3][4].

Other names

NADKNAD kinaseNADK1FLJ13052Poly(P)/ATP NAD kinasedJ283E3.1

Potential mechanisms include enzyme inhibition, leading to depletion of NADP(H) pools and altered cellular redox state[3].