Nicotinamide riboside kinase (NRK)

Nicotinamide riboside kinases (NRKs) are essential enzymes in the nicotinamide adenine dinucleotide (NAD+) salvage pathway, responsible for the phosphorylation of nicotinamide riboside (NR) into nicotinamide mononucleotide (NMN) (Bieganowski & Brenner, 2004). In mammals, the family consists of two isoforms: NRK1, which is ubiquitously expressed and maintains basal NAD+ levels, and NRK2, which is primarily localized to skeletal and cardiac muscle and is significantly upregulated during cellular stress, such as ischemia or heart failure (Fletcher et al., 2017; Diguet et al., 2018). These enzymes are critical for the utilization of exogenous NR and NMN, making them key targets for therapeutic strategies aimed at boosting NAD+ levels to combat age-related physiological decline and metabolic diseases (Ratajczak et al., 2016). NRK activity has been linked to protective effects in neurodegeneration, heart failure, and metabolic disorders by enhancing mitochondrial function and energy metabolism (Khan et al., 2014). However, because NAD+ is also vital for the high metabolic demands of malignant cells, there are emerging concerns that over-activation of this pathway could potentially promote cancer progression or metastasis, particularly in triple-negative breast cancer (Maric et al., 2022).

Other names

NMRKRibosylnicotinamide kinaseNR kinaseNicotinamide riboside kinase 1 (NRK1)Nicotinamide riboside kinase 2 (NRK2)Integrin beta-1-binding protein 3 (ITGB1BP3)Muscle integrin-binding protein (MIBP)

Phosphorylation of nicotinamide riboside (NR) to nicotinamide mononucleotide (NMN) as a rate-limiting step in the NAD+ salvage pathway.