Characteristics of a microsomal cytochrome P-448-mediated reaction. Ethoxyresorufin O-de-ethylation (original) (raw)

Drug metabolism and disposition: the biological fate of chemicals

Abstract

Certain characteristics of ethoxyresorufin O-de-ethylation, as catalyzed by microsomes of liver, lung, and intestine of control and pretreated rats and hamsters, were studied. The results support previous suggestions that the reaction is catalyzed primarily by a 3-methyl-cholanthrene (MC)-inducible mono-oxygenase which has a 448-nm absorption maximum in the reduced-CO difference spectrum. Ethoxyresorufin exhibited a type I binding spectrum with liver microsomes from MC-induced rats, but there was no clear interaction with microsomes from control or phenobarbital (PB)-induced rats. Maximum MC-induction of type I binding and de-ethylase activity coincided with the appearance of a cytochrome P-450 spectrum whose absorption maximum was shifted to 448 nm. Low concentrations of alpha-naphthoflavone (ANF) or benzo[a]pyrene (BP) inhibited the de-ethylation with liver microsomes of MC-treated rats (150 approximately 10(-9)M) but not those of control rats. A kinetic analysis of BP inhibition ...

Richard Mayer hasn't uploaded this paper.

Let Richard know you want this paper to be uploaded.

Ask for this paper to be uploaded.