Organic solvents as modifiers of aldrin epoxidase in reconstituted monooxygenase systems and in microsomes.

  title={Organic solvents as modifiers of aldrin epoxidase in reconstituted monooxygenase systems and in microsomes.},
  author={Thomas Wolff and H Wanders and F. Peter Guengerich},
  journal={Biochemical pharmacology},
  volume={38 23},
To examine the response of individual cytochrome P-450 species catalysing the epoxidation of aldrin (Wolff T and Guengerich FP, Biochem Pharmacol 36: 2581-2588, 1987), monooxygenase systems reconstituted from these species were assayed in the presence of 5% (v/v) = 0.87 M ethanol. The activity of cytochromes P-450PB-B and P-450PB-D, two enzymes inducible by phenobarbital was increased seven-fold. The activity of two other P-450 enzymes purified from these animals was either inhibited by 50%, as… 
Localization of Cytochrome P450 in Membranes: Reconstituted Systems
The most commonly used and convenient system for reconstitution in numerous studies over the years and until now for routine work consists of the appropriate purified cytochrome P450 reductase (reductase) and 30 µM l-α-dilauroylglyceryl-3-phosphatidylcholine (DLPC).
Endogenous and exogenous factors modifying the activity of human liver cytochrome P-450 enzymes.
  • T. Wolff, M. Strecker
  • Biology, Medicine
    Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie
  • 1992
An extended study on human liver cytochrome P-450 performed with liver biopsies of 178 individuals taken for diagnostic purposes assumes that the broad interindividual variation of epoxidase activities is more likely due to the influence of exogenous and endogenous inducers rather than to a genetic polymorphism.
Stimulation of tolbutamide hydroxylation by acetone and acetonitrile in human liver microsomes and in a cytochrome P-450 2C9-reconstituted system.
Overall, the stimulatory effect of both acetonitrile and acetone on tolbutamide hydroxylation was found to be primarily due to a consistent increase in V(max), whereas K(m) was unchanged in both human liver microsomes and the reconstituted CYP2C9 system.
Structural Models for Substrates and Inhibitors of Cytochrome P450 Enzymes
Although a large number of drugs, chemicals, and endogenous compounds are known as substrates or inhibitors of microsomal cytochrome P450 enzymes, systematic attempts to explore substrate and
The activity of human CYP2D6 in low water organic solvents
It is reported here that CYP2D6 colyophilized with trehalose and suspended in n‐decane shows higher activity than in aqueous buffer, and provides an alternative strategy to facilitate the use of this enzyme in synthesis.
The effect of tetrahydrofuran on biological systems: does a hepatotoxic potential exist?
  • D. Moody
  • Chemistry, Medicine
    Drug and chemical toxicology
  • 1991
While there is little evidence to suggest that THF would be a direct (Type I) hepatotoxin at relatively low doses, its ability to inhibit drug-metabolizing reactions, and enhance the absorbance of reactive metabolites, are relatively unexplored avenues for THF to contribute to a hepatotoxic response.
Orientation of cytochromes P450 in the endoplasmic reticulum.
It is concluded that cytochrome P450 is most likely oriented such that the heme is not fixed horizontal to the plane of the membrane of the endoplasmic reticulum and may well lie with the he me perpendicular to the membrane.
Multiplicity of n‐heptane oxidation pathways catalyzed by cytochrome P450
Modeling, mutagenesis, and kinetic studies have demonstrated that the substrate‐binding site of cytochrome P450 is composed of multiple interactive regions that are capable of simultaneously binding
Isoflurane and cytochrome b5 stimulation of 2-chloro-1,1-difluoroethene metabolism by reconstituted rat CYP2B1 and CYP2C6.
In reconstituted CYP2B1, isoflurane generated a type I difference spectrum of approximately twice the magnitude of CDE and stimulated NADPH consumption more so thanCDE and the same quantity of NADPH was consumed when CDE was present with isofLurane as compared with is ofluranes alone.


Aldrin epoxidation, a highly sensitive indicator specific for cytochrome P-450-dependent mono-oxygenase activities.
The results demonstrate that aldrin epoxidation offers a selective and sensitive assay for the activity of mono-oxygenases dependent on cytochrome P-450 forms and suggest that the same or (a) similar form(s) of mono -oxygenase catalyze the ep oxidation in the three different microsomal preparations.
Aldrin epoxidation catalyzed by purified rat-liver cytochromes P-450 and P-448. High selectivity for cytochrome P-450.
Aldrin epoxidation was studied in monooxygenase systems reconstituted from purified rat liver microsomal cytochrome P-450 or P-448, NADPH-cytochrome c reductase, dilauroylphosphatidylcholine and
Identification of the cyanopregnenolone-inducible form of hepatic cytochrome P-450 as a catalyst of aldrin epoxidation.
P-450PCN, P-450PB, and probably other cytochromes P- 450 catalyze aldrin epoxidation, precluding use of this enzyme as a specific marker of a single form of the cytochrome.
Differences in the biochemical properties of aldrin epoxidase, a cytochrome P-450-dependent monooxygenase, in various tissues.
It is confirmed that more than one form of cytochrome P-450 supports aldrin epoxidase in the liver, but it may be a different type, or regulated in a different manner in these tissues.
Rat liver cytochrome P-450 isozymes as catalysts of aldrin epoxidation in reconstituted monooxygenase systems and microsomes.
The results reveal that aldrin epoxidation is a reaction indicative of male specific and of phenobarbital-inducible cytochrome P-450 isozymes in rat liver.
Interaction of liver microsomal cytochrome P-450 and NADPH-cytochrome P-450 reductase in the presence and absence of lipid.
The results lead to the conclusion that the major effect of phospholipids in P-450-based enzyme systems is the facilitation of an active P- 450:NADPH-P-450 reductase complex.
Lack of relationship between debrisoquine 4-hydroxylation and other cytochrome P-450 dependent reactions in rat and human liver.
The results indicate that DQH in the rat and in man reflects the activity of a cytochrome P-450 species not related to various other known cyto Chrome P- 450 functions.
Characterization of three highly purified cytochromes P-450 from hepatic microsomes of adult male rats.
Results of this study indicate that rat hepatic microsomal cytochromes P-450 are composed of at least four hemoproteins with CO-reduced absorbance maxima between 447-448 nm and a minimum of four microsomes are now known to 16 alpha-hydroxylate testosterone.
Relationship between oxidative metabolism of 2-acetylaminofluorene, debrisoquine, bufuralol, and aldrin in human liver microsomes.
It is concluded, based on these multiple cross-correlations, that common cytochrome P-450 isoenzymes are involved in the formation of AAF metabolites, while the metabolism of debrisoquine, bufuralol, and aldrin is unrelated to the metabolic of this carcinogen in human liver microsomes.
Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy.
Studies involving the metabolism of chemical carcinogens were important in the discovery and initial characterization of the cytochrome P-450 enzyme system. The Millers and their associates