Nicotinamide riboside kinase 1 (NRK1) (NRK1)

Nicotinamide riboside kinase 1 (NRK1) is an enzyme that catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN), respectively, serving as a key step in the salvage pathway for NAD+ biosynthesis. NRK1, encoded by the NM RK1 gene, is ubiquitously expressed across tissues, including liver and kidney, and works alongside NRK2 (more muscle-specific) to utilize dietary NR precursors for maintaining cellular NAD+ levels essential for energy metabolism, glycolysis, TCA cycle, oxidative phosphorylation, DNA repair, and calcium signaling. In skeletal muscle, NRK1/2 regulate mitochondrial content, fiber type composition (favoring glycolytic type IIB fibers upon loss), and adaptations during regeneration, where their absence leads to increased NAM salvage, NR accumulation, and transient delays in muscle stem cell differentiation and tissue remodeling despite normal NAD+ levels. Therapeutically, NRK1 activates nucleoside analogs like tiazofurin for anticancer effects by converting them to active monophosphates, highlighting its prodrug kinase role. Crystal structures reveal a bilobal architecture with LID and NMP-binding domains, where residues like Asp36 act as the general base and Asp56/Arg129 recognize ribose hydroxyls. While NRK1 knockout mice show compensatory mechanisms without baseline deficits, disruptions link to metabolic perturbations in stress or damage scenarios, positioning it as a modulator in NAD+-related pathologies rather than a primary disease driver.

Other names

Nicotinamide riboside kinaseNRKNmrk1

Phosphorylation of nicotinamide riboside (NR) to nicotinamide mononucleotide (NMN) for NAD+ production; Activation of anticancer nucleoside analogs like tiazofurin by phosphorylation