Ethoxycoumarin-O-deethylation

Inoue K, Yamazaki H, Shimada T (2000) Characterization of liver microsomal 7-ethoxycoumarin O-deethylation and chlorzoxazone 6-hydroxyl-alion activities in Japanese and Caucasian subjects genotyped for CYP2E1 gene. Arch Toxicol 74 372 378... 

Figure 2 Effects of i.p.-injectedpolysaccharides on the level and activity of cytochrome P450s (CYPs). Mice were intraperitoneally administered polysaccharides and /or MC as described in Figure 1. (A) Microsomal proteins were prepared from the liver, and the total CYP contents and (B) the ethoxycoumarin O-deethylation (ECOD) and (C) ethoxyresorufin O-deethylation (EROD) activities were measured as described in Materials and...

In this study, we have utilized 2,2, 4,4 -tetrachlorobiphenyl and 3,3, 4,4 -tetrachlorobiphenyl as representative non-coplanar and coplanar isomers respectively. The 3,3, 4,4 -tetrachlordbi-phenyl isomer (0.3mmole/kg) induced ethoxycoumarin-and ethoxy-resorufin-O-deethylations in the rainbow trout to a similar extent as did Aroclor 1242 (Table III). However, the non-coplanar 2,2 -4,4 -tetrachlorobiphenyl was without effect upon any of the monooxygenase activities examined. Cytochrome P -450-like activity as determined by ethoxyresorufin-O-deethylation was increased by the planar 3,3, 4,4 -tetrachlorobiphenyl while cytochrome P-450-like activity (benzphetamine-N-demethylation) was unaffected. 

A notable exception to the voltammetric transduction of P450 has been reported by Kara et al. [312]. The authors used a fusion enzyme between rat P450 lAl monooxygenase and yeast NADPH-cytochrome P450 oxidoreduc-tase expressed in Saccharomyces cerevisiae that is immobilized in an agarose layer on the gate of an ISFET for the monitoring of the o-deethylation of 7-ethoxycoumarin to 7-hydroxycoiunarin. As depicted in Eq. (10.12), the... 

Differences in the deuterium isotope effects for the oxidation of carbons adjacent to nitrogen vs oxygen suggest that the two reactions are mediated by different mechanisms. The intramolecular isotope effect for O-deethylation of deuterium substituted 7-ethoxycoumarin is 13 and for O-demethylation of 4-nitroanisole with a trideuterio methyl group is lO - In contrast, an isotope effect of 2-3 is obtained for the N-dealkylation of N-methyl-N-trideuteriomethylaniline The intrinsic isotope effects for O-dealkylation thus approach those for normal carbon hydroxylation reactions, but the isotope effects for N-dealkyla-tion are much lower. 

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