0000000000416825
AUTHOR
Clifford R. Elcombe
SUBSTRATE-ELICITED DISSOCIATION OF THE ISOSAFROLE METABOLITE-CYTOCHROME P-450 COMPLEX AND THE CONSEQUENTIAL REACTIVATION OF MONOOXYGENATION
ABSTRACT The present study was initiated to determine whether the substrate-elicited dissociation of the isosafrole metabolite-cytochrome P-450 complex resulted in increased monooxygenase activity. It was found that the substrates p -nitroanisole and ethoxycoumarin would elicit dissociation, furthermore this dissociation was accompanied by increased dealkylation of the substrates. Benzo(a)pyrene was found not to effect the dissociation of the complex, while biphenyl, which undergoes a similar hydroxylation, was effective.
A novel haemoprotein induced by isosafrole pretreatment in the rat
Abstract Sodium dodecyl sulphate-polyacrylamide gel electrophoresis has been used to demonstrate that pretreatment of rats with isosafrole results in the formation of a novel species of cytochrome P-450 (mol. wt. 54,000) quite distinct from that induced by phenobarbitone pretreatment (mol. wt. 50,000) or 3-methylcholanthrene (mol. wt. 58,000).
The metabolism of mono-(2-ethylhexyl) phthalate (MEHP) and liver peroxisome proliferation in the hamster.
This study has investigated the in vivo metabolism of mono-(2-ethylhexyl) phthalate (MEHP), the initial metabolite of di-(2-ethylhexyl) phthalate in mammals, and the hepatic peroxisome proliferation induced by this compound following multiple oral administration to hamsters. Hamsters received [14C]-MEHP, by gavage, at doses of 50 and 500 mg/kg body wt on each of three consecutive days. Urine was collected every 24 hours and metabolite profiles were determined using capillary gas-chromatography. Multiple high doses of MEHP (500 mg/kg) induced a change in the relative proportions of metabolites produced. As previously reported for the rat, metabolites derived from sequential ω-following by β…
Measurement of substrate-induced oxygen uptake during microsomal drug oxidation using a gold micro-electrode.
1. A resin-coated gold micro-electrode has been used for polarographic determination of oxygen concentration in liver microsomal suspensions from phenobarbital-pretreated rats. 2. The rate of oxygen uptake on addition of an NADPH-regenerating system and the rate after addition of various substrates of the mixed function oxidase system were measured. The rate of oxygen uptake was faster in the presence of substrate than in the presence of NADPH alone. 3. Kinetic constants (Km and V max) for biphenyl, hexobarbital, ethylmorphine, naphthalene and SKF 525-A measured by this technique compare favourably with those obtained either by measurements of NADPH oxidation, or chemical measurements of su…