Cyclodiene epoxide ring hydration by microsomes from mammalian liver and houseflies

The 2014 Bernard B. Brodie Award Lecture—Epoxide Hydrolases: Drug Metabolism to Therapeutics for Chronic Pain

“…The earliest works on microsomal epoxide hydrolase (mEH or EH1, EC 3.3.2.9) were only possible because of simultaneous work done on metabolites of cyclodiene epoxides by Gerry Brooks (Brooks et al, 1970;Morisseau and Hammock, 2008) and arene epoxides in John Daly's group (Jerina et al, 1968) (Fig. 1; Table 2).…”

“…Jerina et al (1968) had previously shown that hydration of 1,2-naphthalene oxide occurred in the rat liver microsomes; however, characterization of the enzyme responsible (mEH) had not yet been performed. In his seminal article, Brooks showed that hydration of the chlorinated cyclodiene epoxides occurred through microsomal enzymes (Brooks et al, 1970). This in turn led to Brooks' development of the hypothesis that inhibiting mEHs could lead to synergism (Brooks, 1973;Morisseau and Hammock, 2008).…”

Enzymes Involved in the Metabolism of Plant Allelochemicals

“…Much less is known about the subcellular distribution and specificity of epoxide hydrolases in arthropod tissues, although both trans and cis epoxides are hydrolyzed in cytosolic and microsomal fractions Ottea and Hammock, unpubl.). A microsomal enzyme was purified from midguts of the southern armyworm (Mullin and Wilkinson, 1980) and occurs in many other insects including the blow fly, Calliphora erythrocephala Meigen (Diptera: Calliphoridae), the house fly (Brooks et al, 1970); the fruit fly (Baars, 1980), the mealworm (Brooks, 1973), the flour beetle, Tribolium .castaneum (Herbst) (Coleoptera: Tenebrionidae) (Cohen, 1981), the Madagascar cockroach (Slade et al, 1975), the American cockroach (Nelson and Matsumura, 1973), the fall armyworm Yu and Hsu, 1985), the orange tortrix and its ectoparasite, Oncophanes americanus (Weed) (Hymenoptera: Braconidae) , the honey bee, Apis mellifera L. (Hymenoptera: Apidae) (Yu et al, 1984), and in addition in 33 other insect species Mullin, Chapter 5 in this text). It also occurs in the twospotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), and the predatory mite Amblyseius fallacis (Garman) (Acari: Phytoseiidae) .…”

Microsomal Oxidation and Insecticide Metabolism

“…9). Trans-6,7-dihydroxydihydroaldrin (trans-aldrindiol) has been identified as a urinary metabolite of dieldrin (epoxide of aldrin) from rabbit and rat (Korte and Arent, 1965;Matthews et at., 1971) and as an in vitro metabolite of several microsomal systems ( Matthews and Matsumura, 1969;Brooks et at., 1970). Whether the trans isomer is the direct metabolite of hydration is uncertain in view of the discovery in the rat liver of an epoxide epimerase which unidirectionally epimerizes the cis to the trans isomer (Matthews and McKinney, 1974).…”