INVITRO CHARACTERISTICS OF GUINEA-PIG LUNG AROMATIC AZAHETEROCYCLE N-METHYLTRANSFERASE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 13  (6) , 658-663
Abstract
The in vitro characteristics of guinea pig lung aromatic azaheterocycle N-methyltransferase have been determined, using R-(+)-nicotine as substrate. The enzyme is a cytosolic, S-adenosyl-L-methionine-dependent N-methyltransferase exhibiting apparent KM values of 14.2 and 13.2 .mu.M for R-(+)-nicotine and S-adenosyl-L-methionine, respectively. The pH and temperature optima for enzyme activity were 7.4 and 37.degree. C, respectively. An interesting stereospecificity was demonstrated for nicotine enantiomers toward the N-methyltransferase. S-(-)-Nicotine acts as a competitive inhibitor (KI = 6.25 .times. 10-5 M) of the N-methylation of its optical antipode by the above enzyme. The enzyme also exhibits potent feedback inhibition by S-adenosyl-L-homocysteine (KI = 3.2 .times. 10-5 M). Neither S-(.sbd.)-cotinine nor nicotinamide is a substrate for the enzyme; however, the latter compound did act as a weak competitive inhibitor (KI = 41.8 .times. 10-5 M) of the N-methylation of R-(+)-nicotine.