Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: ceh 2
 185 document(s) hit in 31,850,051 MEDLINE articles (0.01 seconds)

Six different 1,2-epoxycycloalkanes, whose rings were constituted of 5 to 12 carbon atoms, were tested as possible inhibitors of epoxide-metabolizing enzymes and substrates for the microsomal and cytosolic epoxide hydrolases (mEH, cEH) in mouse liver. The geometric configurations and the relative steric hindrances of these epoxides were estimated from their ease of hydrolysis in acidic conditions to the corresponding diols, their abilities to react with nitrobenzylpyridine, and the chemical shifts of the groups associated with the oxirane rings measured by proton and 13C-NMR. The cyclopentene, -hexene, -heptene, -octene and -decene oxides adopted mainly a cis-configuration. By contrast, cyclododecene oxide presented a trans-configuration. Steric hindrance increased with the size of the ring and was particularly strong when cyclooctene, -decene and -dodecene oxides were considered. With the exception of cyclohexene oxide, all the compounds were weak inhibitors of EH and glutathione S-transferase (GST) activities. Cyclohexene oxide exhibited a selective inhibition of the mEH with an I50 of 4.0.10(-6) M. As the size of the ring increased, inhibitory potency was gradually lost. The cEH and the GST activities were less sensitive to the inhibitory effects of these epoxides (I50, 1 mM or above). A marked difference between the substrate selectivities of mEH and cEH for these epoxides was observed. The mEH hydrated all of the cyclic epoxides, although some of them at a very low rate; the best substrate was the cycloheptene oxide (2.3 nmol/min/mg protein). On the other hand, cyclodecene oxide was a substrate of cEH, but no diol formation was detected when cyclopentene, -hexene and -dodecene oxides were incubated with cytosolic enzyme.
 ...
PMID:1,2-Epoxycycloalkanes: substrates and inhibitors of microsomal and cytosolic epoxide hydrolases in mouse liver. 339 52