Dog liver N-methyltransferase. A drug-metabolizing enzyme.
A non-specific N-methyltransferase was demonstrated in dog liver. This enzyme is different from other N-methylating systems, especially in terms of substrate and species specificity. The enzyme catalyzes the methylation of a variety of endogenous and exogenous amines; of the compounds studied, SK&F 64139 (7,8-dichloro-1,2,3,4-tetrahydroisoquinoline) was found to be the best substrate. The enzyme utilized S-adenosylmethionine but not 5-methyltetrahydrofolate as a methyl donor, and it had a pH optimum at 8.0. Study of SK&F 64139 with the partially purified enzyme indicated that this dog liver N-methyltransferase had very low Km and high Vmax values for SK&F 64139. Methylation of SK&F 64139 was not observed with the monkey or rat liver enzyme preparation. This finding is in accordance with the fact that SK&F 64139 is methylated extensively in the dog, but not in other species. The ability of this enzyme to methylate a number of arylalkylamines suggests its possible importance in drug biotransformation.
D000818:Animals; D004285:Dogs; D005260:Female; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008252:Macaca fascicularis; D008297:Male; D008780:Methyltransferases / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D051381:Rats; D013045:Species Specificity; D013379:Substrate Specificity
D008780:Methyltransferases