Cytosolic NAD+ kinase (NADK) catalyses the transfer of a phosphate group from ATP to NAD+, forming NADP+. This is the only way to generate NADP+ in all living organisms. NADK is tetrameric and requires one divalent metal such as Zn2+ per subunit to function correctly (Lerner et al. 2004).
NAD kinase is the sole NADP(+) biosynthetic enzyme. A cytosolic form of NAD kinase is already characterised but recently, a mitochondrial form has been found to exist. Mitochondrial NAD kinase 2 (NADK2 aka C5orf33, MNADK, NADKD1) uses ATP to phosphorylate NAD+ to NADP+ (Ohashi et al. 2012). NADK2 is ubiquitously expressed and is more abundant than its cytosolic counterpart. Defects in NADK2 can cause 2,4-dienoyl-CoA reductase deficiency (DECRD), a rare, autosomal recessive, inborn error of polyunsaturated fatty acids and lysine metabolism, resulting in mitochondrial dysfunction (Houten et al. 2014).