Nicotinamide riboside kinase

Figure 2. NAD biosynthesis and its role for regulatory pathways in mammalian cells. Note added in proof A recent study demonstrates an alternative biosynthetic route of NAD, not indicated in Figure 2 a specific kinase has been found which converts nicotinamide riboside to NMN (Bieganowski P, Brenner C Cell 2004 117 495-502). Nicotinamide riboside could be an important nutritional factor. Also, nicotinamide riboside kinase could be involved in the conversion of the anticancer drugtiazofiirin to its active form.

Figure 7.3 NAD recycling. Humans have two metabolic pathways that are able to recycle nicotinamide. NAD-consuming enzymes (ARTs, PARPs, sirtuins) break down NAD to nicotinamide and ADP-ribosyl product. Nicotinamide by the enzymatic action of nicotinamide phosphoribosyltransferase (NAMP/PBEF) and nicotinamide/nicotinate-mononucleotide-adenyltransferases isoenzymes (NMATl-3) is then retransformed to NAD. In a second pathway, nicotinamide riboside is phosphorylated by nicotinamide riboside kinase (NRK 1,2) to nicotinamide mononucleotide. Subsequently, nicotinamide mononucleotide is converted to NAD by the catalytic action of NMNATs.

Pyridine Nucleotides. Nucleoside phosphorylase is capable of using the base nicotinamide. The product of the reaction of this base with ribose-l-phosphate is nicotinamide riboside. The formation of the corresponding nicotinamide mononucleotide is catalyzed by a typical kinase, using ATP. A specific enzyme purified from human erythrocytes has been shown to form nicotinamide mononucleotide by a second mechanism in which PRPP and nicotinamide react to form inorganic pyrophosphate and... 

Nicotinic Add Metabolism. The sequence of reactions leading to the formation of pyridine compounds is of particular interest as a source of nicotinic acid. Nutritional, isotopic, and genetic experiments have all shown that tryptophan and its metabolic derivatives including 3-hydroxy-anthranilic acid are precursors of nicotinic acid in animals and in Neuro-spora. The terminal steps in this sequence are not known. Under certain physiological conditions an increase in picolinic carboxylase appears to reduce nicotinic acid synthesis. This implies a common pathway as far as the oxidation of 3-hydroxyanthranilic acid. Whether quinolinic acid is a precursor of nicotinic acid is still uncertain. The enzyme that forms the amide of nicotinic acid also has not been isolated. Subsequent reactions of nicotinamide include the formation of the riboside with nucleoside phosphorylase and methylation by nicotinamide methyl-kinase. In animals W-methylnicotinamide is oxidized to the corresponding 6-pyridone by a liver flavoprotein. Nicotinic acid also forms glycine and ornithine conjugates. Both aerobic and anaerobic bacteria have been found to oxidize nicotinic acid in the 6-position. ... 

---