Some cytochrome P450 enzymes epoxidize unsaturated substrates, but this activity has not been described for the steroid hydroxylases. Physiologic steroid substrates, however, lack carbon-carbon double bonds in the parts of the pregnane molecules where steroidogenic hydroxylations occur. Limited data on the reactivity of steroidogenic P450s toward olefinic substrates exist, and the study of occu...

Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play an important role in blood pressure regulation, protection against ischemia-reperfusion injury, angiogenesis, and inflammation. Epoxide hydrolases metabolize EETs to their corresponding diols (dihydroxyeicosatrienoic acids; DHETs) which are biologically less active. Microsomal epoxid...

The tumorigenicity of the (+)- and (-)-enantiomers of the diastereomeric bay-region benz(a)anthracene 3,4-diol-1,2-epoxides was evaluated in two mouse tumor models. In an initiation-promotion experiment on mouse skin, a single topical application of 0.1 or 0.4 mumol of the benz(a)anthracene diol-epoxides was followed by 25 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate. Of the fou...

The mechanical properties of graphene oxide (GO) are of great importance for applications in materials engineering. Previous mechanochemical studies of GO typically focused on the influence of the degree of oxidation on the mechanical behavior. In this study, using density functional-based tight binding simulations, validated using density functional theory simulations, we reveal that the defor...

Administration of the antioxidant 2(3)-tert-butyl-4-hydroxyanisole (BHA) in the diet caused a marked increase in the specific activity of epoxide hydratase (EC 4.2.1.63) in hepatic microsomes of CD-1 mice. The increases in epoxide hydratase activities produced by BHA were far greater (11-fold) than were those produced by the administration of well-known enzyme inducers such as 3-methylcholanthr...

Administrationof the antioxidant 2(3)-tert-butyl-4-hy droxyanisole(BHA)in the diet causeda markedincrease in the specific activity of epoxide hydratase (EC 4.2.1.63) in hepatic microsomesof CD-i mice. The increases in epoxide hydratase activities produced by BHA were far greater (11-fold)than were those producedby the admin istrationof well-knownenzymeinducerssuchas 3-meth ylcholanthrene,phenob...

The structural features of polycyclic polyether natural products can, in some cases, be traced to their biosynthetic origin. However in case that are less well understood, only biosynthetic pathways that feature dramatic, yet speculative, epoxide-opening cascades are proposed. We summarize how such epoxide-opening cascade reactions have been used in the synthesis of polycyclic polyethers (see s...

Epoxide hydrolase and glutathione S-transferase activities toward trans- and cis-stilbene oxides were measured in 3 strains of Drosophila melanogaster. Differences in age dependence, substrate selectivity and subcellular location were detected suggesting the presence of multiple forms of these enzymes. In addition, interstrain differences indicate the presence of genetic variation for epoxide h...

The major mutational hot spots in human cancers occur at CpG sequences in the p53 gene. It is generally presumed that the majority of mutations at these sites result from the endogenous deamination of methylated cytosine. Using a UvrABC incision method, we have found that cytosine methylation greatly enhances guanine alkylation at all CpG sites in the p53 gene by a variety of carcinogens, inclu...

The distribution of rat liver epoxide hydrolase in various subcellular fractions was investigated by immuno-electron-microscopy. Ferritin-linked monospecific anti-(epoxide hydrolase) immunoglobulins bound specifically to the cytoplasmic surfaces of total microsomal preparations and smooth and rough microsomal fractions as well as the nuclear envelope. Specific binding was not observed when the ...