Epoxide-containing compounds are cyclic ethers that can constitute a toxic hazard to the cell due to the reactivity of the strained three-membered ring. For example, some reactive polycyclic aromatic hydrocarbon epoxides bind to DNA, leading to mutagenic and carcinogenic effects.85 In most cases, however, epoxides are of lower reactivity and often constitute intermediates in biological pathways, notably those involving arachidonic acid epoxides.86 Regardless of the pathway involved, epoxide hydrolases (EC 188.8.131.52) catalyze the nucleophilic addition of water to the substrate.87
In most cases, reaction is initiated by attack of an enzyme nucleophile (usually Asp) on the epoxide to generate an acyl intermediate that is subsequently hydrolyzed by a water molecule that has been activated by the other members of the catalytic triad. This results in the formation of vicinal diols, except in the case of leukotriene A4 hydrolases, which catalyze formation of a 5,12-diol product due to the conjugated nature of the substrate.
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