Nicotinamide phosphoribosyltransferase

The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Srr2 activity in mammalian cells. The Journal of Biological Chemistry, 279, 50754—50763. 

Figure 8.2. Synthesis of NAD from nicotinamide, nicotinic acid, and qninolinic acid. Quinolinate phosphoribosyltransferase, EC 2.4.2.19 nicotinic acid phosphoribosyl-transferase, EC 2.4.2.11 nicotinamide phosphoribosyltransferase, EC 2.4.2.12 nicotinamide deamidase, EC 3.5.1.19 NAD glycohydrolase, EC 3.2.2.S NAD pyrophosphatase, EC 3.6.1.22 ADP-ribosyltransferases, EC 2.4.2.31 and EC 2.4.2.36 and poly(ADP-ribose) polymerase, EC 2.4.2.30. PRPP, phosphoribosyl pyrophosphate.

Tarrant, J.M., Dhawan, P., Singh, J., Zabka, T.S., Clarke, E., DosSantos, E., Dragovich, P.S., Sampath, D., Lin, T., McCray, B., La, N., Nguyen, T., Kauss, A., Dambach, D., Misner, D.L., Diaz, D., Uppal, H. (2015). Preclinical models of nicotinamide phosphoribosyltransferase inhibitor-mediated hematotoxicity and mitigation by co-treatment with nicotinic acid. Toxicology Mechanisms and Methods, 25, 201-211. 

Diaz, D., and Uppal, H. (2015). PrecUnical models of nicotinamide phosphoribosyltransferase inhibitor-mediated hematotoxicity and mitigation by co-treatment with nicotinic acid. Toxicol Mech Methods 25(3), 201-211. 

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.

Imai, S., 2009. Nicotinamide phosphoribosyltransferase (NAMPT) a link between NAD biology, metabolism, and diseases. Current Pharmaceutical Design. 15 20-28. 

Rongvaux, A., Shea, R.J., Mulks, M.H., Gigot, D., Urbain, J., Leo, O., and Andris, F., 2002. Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis. European Journal of Immunology. 32 3225-3234. 

Figure 2 NAD metabolism. Tip = tryptophan, 3-HK = 3-hydroxykynurenine, 3-HA = 3-hydroxyanthranilic acid, ACMS = a-amino-P-carboxymuconate- -semialdehyde, AMS = a-aminomuconate- -semialdehyde, NaMN = nicotinic acid mononucleotide, NMN = nicotinamide mononucleotide, NaAD = nicotinic acid adenine dinucleotide. For other abbreviations, see Figure 1. (1) tryptophan oxygenase [EC 1.13.11.11], (2) formy-dase [EC 3.5.1.9], (3) kynurenine 3-hydroxylase [EC 1.14.13.9], (4) kynureninase [EC 3.7.1.3], (5) 3-hydroxyanthranilic acid oxygenase [EC 1.13.11.6], (6) nonenzymatic, (7) aminocarboxymuconate-semialdehyde decarboxylase [EC 4.1.1.45], (8) quinolinate phos-phoribosyltransferase [EC 2.4.2.19], (9) NaMN adenylyltransferase [EC 2.7.2.18], (10) NAD synthetase [EC 6.3.5.1], (11) NAD kinase [EC 2.7.1.23], (12) NAD" glycohydro-lase [EC 3.2.2.5], (13) nicotinamide methyltransferase [EC 2.2.1.1], (14) 2-Py-forming MNA oxidase [EC 1.2.3.1], (15) 4-Py-forming MNA oxidase [EC number not given], (16) nicotinamide phosphoribosyltransferase [EC 2.4.2.12], (17) NMN adenylytransferase [EC 2.7.71], (18) nicotinate phosphoribosyltransferase [EC 2.4.2.11], (19) nicotinate methyltransferase [EC 2.7.1.7], and nicotinamidase [EC 3.5.1.19]. Solid line, biosynthesis dotted line, catabolism.

M Rocchingiani, V Michaeli, JA Duley, HA Simmonds. Determination of nicotinamide phosphoribosyltransferase activity in human erythrocytes high-performance liquid chromatography-linked method. Anal Biochem 205 334-336, 1992. 

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