The hydration of sterically hindered epoxides by epoxide hydrolase of the rat and rabbit.
The hydration of the sterically-hindered epoxides dieldrin (HEOD) (1,2,3,4, 10,10-hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-exo-1,4-endo-5,8- dimethanonaphthalene) and MME (1,2,3,4,9,9-hexachloro-1,4,4a,5,8,8a-hexahydro-6-methyl-6,7 epoxy 1,4-methanonaphthalene) was studied in pig and rabbit liver microsomes, and in apparently homogeneous preparations of epoxide hydrolase purified from liver microsomes of the rat and rabbit. A non-hindered substrate, HEOM (1,2,3,4,9,9-hexachloro-1,4,4a,5,6,7,8,8a-octahydro exo-6,7 epoxy-1,4 methano naphthalene) was used to assay both the enzyme preparations and the microsomes for epoxide hydrolase activity. The purified enzymes had more stable activity when incorporated into suspensions of phospholipid derived from rat liver microsomes than when used alone, so this preparation was used for long-term incubation with HEOD and MME. Activity towards the three substrates followed the sequence HEOM much greater than MME much much greater than HEOD, in the approximate ratios 1.5 X 10(6):10(4) activity towards dieldrin being only 0.0065-0.052 pmol/mg prot/min. The sole product of MME hydration was identified as a trans diol. The only product identified in the case of HEOD hydration by microsomes or enzyme preparations was the trans diol so there was no evidence for a significant metabolic pathway through the cis diol which is mediated by epoxide hydralase.
D000818:Animals; D004026:Dieldrin / Q000031:analogs & derivatives / Q000378:metabolism*; D004732:Endrin / Q000031:analogs & derivatives / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D011817:Rabbits; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014867:Water
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D014867:Water; C010585:HEOM; C020415:MME; D004851:Epoxide Hydrolases; D004026:Dieldrin; D004732:Endrin