Rate parameter changes by added albumin in the microsomal oxidative demethylation of deuteriated and non-deuteriated 4-methoxyanisole.
Bovine serum albumin (BSA) added to the reaction medium for the oxidative demethylation of 4-methoxyanisole and its "di-CD3" isotopomer ([d6]methoxyanisole), when catalyzed by liver microsomes from untreated rats, decreased the Km values and increased the V(max)/Km (= V/K) values. The Vmax values were not markedly altered. The values for the deuterium isotope effect on V(max) and V/K for the reaction with this isotopomer were between 2.2 and 2.8, and that on Km was close to unity. The magnitude of the isotope effect was not significantly changed by adding BSA. The intramolecular isotope effect with [mono-CD3]4-methoxyanisole ([d3]methoxyanisole) in liver microsomes from untreated rats was between 10.3 and 10.8, which was not significantly changed by BSA. Liver microsomes from rats treated with phenobarbital resulted in the intramolecular isotope effect value in the absence of BSA being between 7.2 and 9.1, which was not significantly altered by BSA. Based on these data, the calculated apparent rate constant for the enzyme-substrate complex formation was markedly increased by up to about 1.9- and 3.5-fold by 1% and 2% of BSA added, respectively.
Masuda
M
M
Department of Agricultural Chemistry, Kyoto University, Japan.
Kishimoto
D
D
Kurihara
N
N
D000818:Animals; D000840:Anisoles / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D007553:Isotope Labeling; D008297:Male; D008745:Methylation; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D013379:Substrate Specificity
D000840:Anisoles; C031200:1,4-dimethoxybenzene; D012710:Serum Albumin, Bovine; D003577:Cytochrome P-450 Enzyme System; D003903:Deuterium; D010634:Phenobarbital