Substrate specificity of nicotinamide methyltransferase isolated from porcine liver.
Nicotinamide methyltransferase (EC 2.1.1.1) has been purified over 1300-fold from porcine liver. The enzyme is electrophoretically homogeneous, exhibiting a relative molecular mass of 27,000. In addition to acting on nicotinamide and close structural analogs such as thionicotinamide and 3-acetylpyridine, the enzyme actively accommodates poor analogs such as quinoline, isoquinoline, and 1,2,3,4-tetrahydroisoquinoline as methyl group acceptors. The enzyme may thus have the function of detoxicating numerous alkaloids in vivo. In some cases, the action of the enzyme might paradoxically increase the toxicities of substrates, but the hepatotoxic antibiotic pyrazinamide, which we considered as potentially such an enzyme-activated electrophile, did not function detectably as a substrate for the isolated enzyme.
D000818:Animals; D005990:Glycerol / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008780:Methyltransferases / Q000378:metabolism*; D008970:Molecular Weight; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism; D050903:Nicotinamide N-Methyltransferase; D011718:Pyrazinamide / Q000031:analogs & derivatives / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D011804:Quinolines / Q000378:metabolism; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013552:Swine; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D011725:Pyridines; D011804:Quinolines; D013438:Sulfhydryl Compounds; D044005:Tetrahydroisoquinolines; D009243:NAD; D009536:Niacinamide; D011718:Pyrazinamide; C014843:1,2,3,4-tetrahydroisoquinoline; C054717:pyrazinamide methiodide; C037219:quinoline; D008780:Methyltransferases; D050903:Nicotinamide N-Methyltransferase; C039109:isoquinoline; D005990:Glycerol