Arene oxides enzymatic formation

The principal pathway by which unsubstituted and many substituted aromatic hydrocarbons are metabolized in mammals consists of the initial formation of arene oxides, which undergo a variety of enzymatic and nonenzymatic reactions prior to excretion of the resulting more polar, oxidized hydrocarbons via bile or urine. Taken together, these pathways represent an attempt on the part of the animal to detoxify or eliminate such nonpolar xenobiotic substances for which it has no apparent use. Although detoxification is the probable role of the arene oxide pathway, it is equally clear that chemically reactive species mediate this process. Thus, studies over the past several years have either implicated or established arene oxides in a causative role in such adverse biological reactions as cytotoxicity, mutagenesis, and carcinogenesis via covalent interaction of arene oxides with biopolymers,... 

Nucleophilic. In view of the ability of epoxides to become hydrated to the diol under aqueous alkaline conditions, the analogous addition of water to epoxides by enzymes will be considered in this section. The en mes responsible for epoxide hydration (epoxide hydrases) in animal liver systems have been purified, assayed using [7- H]styrene oxide,and tested for substrate and inhibitor -ass specificity. The current interest in these epoxide hydrases is mainly due to their close association with aryl monooxygenase enzymes and thus the total metabolism of olefinic and arene substrates via epoxides) in animals. The isolation of the antibacterial compounds aeroplysinin-1 (358) and aeroplysinin-2 (359) from the sponge Verongia aerophoba might be explained by the initial enzymatic formation of the unstable arene oxide (357), which can subsequently be hydrated by an epoxide hydrase enzyme, to form what the authors consider... 

The enzymatic hydroxylations play a crucial role in detoxification and excretion of toxic arenes and in drug metabolism. The enzymatic degradation of aromatics occurs via two different pathways (i) monooxygenase-mediated formation of arene oxide followed by enzymatic hydrolysis to yield tram-l,2-dio and its further metabolism and (ii) dioxygenase-catalyzed arene cis-dihydroxylation... 

---