The nature of microsomal monooxygenase inhibition by cimetidine.
A kinetic investigation of the inhibitory effect of cimetidine on the O-dealkylation of 7-ethoxyresorufin by rat liver microsomes has yielded linear Lineweaver-Burk plots which intersect in the second quadrant. Though technically compatible with non-competitive inhibition, the results are shown to be readily explained by the more realistic molecular concept of competitive inhibition by invoking the involvement of cytochrome P-450 isoenzymes with widely different KI values. Microsomal monooxygenase heterogeneity is also shown to provide a plausible explanation of other published results signifying the departure of chloramphenicol and phenacetin from the concept of competitive inhibition despite competition with substrate for the active-site haem group of cytochrome P-450.
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002927:Cimetidine / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System; D006418:Heme / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008862:Microsomes, Liver / Q000201:enzymology*; D010078:Oxazines / Q000378:metabolism; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D010078:Oxazines; D006418:Heme; C007649:ethoxyresorufin; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases