| First Author | Scheller T | Year | 1996 |
| Journal | Pharmacogenetics | Volume | 6 |
| Issue | 1 | Pages | 43-53 |
| PubMed ID | 8845860 | Mgi Jnum | J:32997 |
| Mgi Id | MGI:80485 | Doi | 10.1097/00008571-199602000-00003 |
| Citation | Scheller T, et al. (1996) Mouse liver nicotinamide N-methyltransferase pharmacogenetics: biochemical properties and variation in activity among inbred strains. Pharmacogenetics 6(1):43-53 |
| abstractText | Nicotinamide N-methyltransferase (NNMT) catalyses the N-methylation of nicotinamide and other pyridines. Human liver NNMT activity shows large individual variations and a bimodal frequency distribution, raising the possibility that this activity, like those of many other methyltransferase enzymes, might be regulated by a genetic polymorphism. In an attempt to develop an experimental animal model for pharmacogenetic studies of NNMT, we determined optimal conditions for the measurement of hepatic NNMT activity in C57BL/6J mice. Mouse liver NNMT was a cytoplasmic enzyme with a pH optimum of 7.4 and apparent Km values for nicotinamide and S-adenosyl-L-methionine, cosubstrates for the reaction, of 370 and 6.5 microM, respectively. These properties were very similar to those of human liver NNMT, as was the relative sensitivity of the mouse liver enzyme to a series of methyltransferase inhibitors. Hepatic NNMT activity was then measured in tissue from male mice of 10 inbred strains. Average levels of NNMT activity in these strains varied by up to 14-fold and ranged from 1.13 +/- 0.18 U per mg protein (mean +/- SEM, n = 6) for C3H/HeJ mice to 16.0 +/- 1.16 U per mg protein in C57BR/cdJ animals. Average hepatic NNMT activities in female mice of six strains in which both sexes were studied varied from five-fold higher than those in males for low activity' strains, to not significantly different for high activity' strains. A series of properties of NNMT was then compared in hepatic cytosol |
