Epoxide hydrolase activities

Table 10.2. Epoxide Hydrolase Activity in Human Liver Microsomes [119]... 

N. R. Kitteringham, C. Davis, N. Howard, M. Pirmohamed, B. K. Park, Interindividual and Interspecies Variation in Hepatic Microsomal Epoxide Hydrolase Activity Studies with cw-Stilbene Oxide, Carbamazepide 10,11-Epoxide and Naphthalene , J. Pharmacol. Exp. Ther. 1996, 278, 1018 - 1027. 

For a long time it was generally accepted that epoxide hydrolases are predominantly found in mammals [25,26], although epoxide hydrolase activities had been detected in bacteria [34,35] or fungi [36,37] quite some years ago. This view was too simplistic, since these enzymes have now been detected in many bacteria [38-40], fungi [41], as well as in red yeast [42]. Moreover, epoxide hydrolase activity has also been demonstrated in plants [43] and insects [44]. 

It is noteworthy that, in contrast to mammalian systems, the majority of bacterial strains exhibited sufficient activity even when the cells were grown under non-optimized conditions. Since enzyme induction is still a largely empirical task, cells were grown on standard media in the absence of inducers. Furthermore, all attempts to induce epoxide hydrolase activity in Pseudomonas aeruginosa NCIMB 9571 and Pseudomonas oleovorans ATCC 29347 by growing the cells on an alkane (decane) or alkene (1-octene) as the sole carbon source failed [27]. 

K (peptidase activity) = 0.018 pM IC50 (epoxide hydrolase activity) = 0.2 pM... 

Fish are extremely good biliary concentrators of drugs. Molecular weight and polarity concerns for biliary elimination are basically similar to mammals, but bile formation in fish is nearly 50 times slower than mammals. As a result, fish have the capacity to biotransform a variety of substrates, although the rates generally observed are lower than in many mammalian species. Sufficient evidence exists to indicate that glucuronyl transferase, sulfotransferase, glutathione-S-transferase, and epoxide hydrolase activities in fish are, at least qualitatively, similar to those found in mammals (23, 24). 

The intrinsic rates of formation of monoepoxides in human, rat and mouse liver microsomes are roughly similar, when epoxide hydrolase is inhibited, whereas the amount of monoepoxides at the end of incubation is two and even 15 times higher in mouse liver microsomes than in rat and human liver microsomes, respectively (Bogaards et al., 1996). Thus, differences in epoxide hydrolase activity between different species may be of importance for toxicological outcomes. 

Pentachloroethane given to rats by gavage during a two-year study caused chronic, diffuse kidney inflammation and renal papilla mineralization. A single dose also reduced hepatic cytochrome P450 content and microsomal epoxide hydrolase activities. Inhalation exposure of rabbits to pentachloroethane decreased their total antibody titres (lARC, 1986). 

Bickers DR, Dutta-Choudhury T, Mukhtar H. 1982. Epidermis A site of drug metabolism in neonatal rat skin. Studies on cytochrome P-450 content and mixed-function oxidase and epoxide hydrolase activity. Mol Pharmacol 21 239-247. 

Gill SS, Kaur S. 1987. Hepatic epoxide hydrolase activities and their induction by clofibrate and dicthylhcxylphthalatc in various strains ofmice. Biochem Pharmacol 36 4221-4227. 

Zocher, F., Enzelberger, M.M., Bomscheuer, U.T., Hauer, B. and Schmid, R.D. (1999) A colorimetric assay suitable for screening epoxide hydrolase activity. Analytica Chimica Acta, 391, 345-351. 

Mateo, C., Archelas, A. and Furstoss, R. (2003) A spectrophotometric assay for measuring and detecting an epoxide hydrolase activity. Analytical Biochemistry, 314,135-141. 

Epoxide rings of alkene and arene compounds are hydrated to form trans-diols. The enzymes that catalyze the addition of a molecule of water to an epoxide ring to yield diols are called epoxide hydrolases (also known as epoxide hydrases). Epoxide hydrolase activity has been detected in numerous species of insects. Enzymatic epoxide hydration of certain cyclodiene insecticides and their analogs has been demonstrated in the housefly, blowfly (Calliphora erythrocephala), yellow mealworm (Tenebrio molitor), Madagascar cockroach (Gromphadorhina portentosa), southern army worm (Spodoptera eridania), and red flour beetle (Tribolium castaneum). Epoxide hydrolase is also important in the metabolism of juvenile... 

Table 9.5 Epoxide hydrolase activity in liver microsomes from various species of animals...

Methyl esters prepared from undecylenic acid and containing an episulfide group were tested as inhibitors of JH III epoxide hydrolase activity to evaluate its biological role in insects <2005MI140>. 

COMPARISON OF EPOXIDE HYDROLASE ACTIVITY IN LIVER MICRO-SOMES FROM PHENOBARBITAL-TREATED RATS WITH THAT OF THE PURIFIED ENZYME IN THE PRESENCE OF LIPID FOR A SERIES OF ARENE OXIDES ... 

Epoxide hydrolase activity is present in most mammalian tissues and is high in the endoplasmic reticulum and cytosol of the liver. Humans appear to have considerable intersubject variability in the activity of epoxide hydrolase that may impact on individual susceptibility to the toxic action of certain epoxides This variability argues for the existence of several epoxide hydrolases. 

There are two distinct types of epoxide hydrolases, both widely distributed in mammalian tissues. One type is localized primarily in the endoplasmic reticulum, the second in the cytosol. The microsomal and cytosolic enzymes have different properties, including substrate selectivities. Several inducers of xenobiotic metabolizing enzymes, including pheno-barbital, planar PCB congeners, and ra s-stilbene oxide, selectively increase (induce) microsomal, but not cytosolic, epoxide hydrolase activity. 

TNT increases UDPglucuronsyltransferase in the liver and kidneys. It increases renal epoxide hydrolase activity. Animal studies have suggested covalent binding between TNT and macromolecular proteins including serum albumin, hemoglobin (Hb), hepatic and renal proteins, and possibly lens protein. The Hb adduct was dose dependent. Macromolecular binding is likely to be correlated with toxic effects ... 

Roe, R., Kallapur, V., Linderman, R. J. and Viviani, F. (2005) Organic synthesis and bioassay of novel inhibitors of JH III epoxide hydrolase activity from fifth stadium cabbage loopers, Trichoplusia ni. Pestic. Biochem. Physiol., 83, 140-154. 

The presence of epoxide hydrolase activities of fungal cells has been described... 

The presence of epoxide hydrolase activities of fungal cells has been described by several authors [196-201]. However, the real breakthrough in the use of such enzymes for preparative scale synthesis was developed by the group of Furstoss et al. One of their first results was the description of the efficient resolution of racemic geraniol AT-phenylcarbamate by a culture of the fungus A. niger, leading... 

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