Aliphatic 3,4-epoxyalcohols: Metabolism by epoxide hydrase and mutagenic activity

• Published in: Biochimica et biophysica acta. General subjects Vol. 544; no. 3; pp. 504 - 513
• Main Authors: Ortiz de Montellano, Paul R., Boparai, Amrit S.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.01.1978
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/0304-4165(78)90325-2

Rabbit hepatic microsomal epoxide hydrase catalyzes the rapid hydrolysis of 1,2-epoxy-4-heptanol to 1,2,4-heptanetriol. Both diastereomers of the substrate are hydrolyzed, and both product diastereomers are formed. Similarly, both cis- and trans-3,4-epoxy-1-hexanol are hydrolyzed, albeit more slowly, to give 1,3,4-hexanetriol. The trans isomer gives exclusively one diastereomer ( erythro) of the triol, while the cis isomer gives the other diastereomer ( threo). The product expected if a primary cationic intermediate were to be formed and trapped intramolecularly during the hydrolysis of 1,2-epoxy-4-heptanol, 2-propyl-4-tetrahydrofuranol, was not observed. A comparison of the mutagenic activity in the Ames test of 1-heptane, 1-hepten-4-ol, 1,2-epoxyheptane, and 1,2-epoxy-4-heptanol revealed that only the latter is a detectable mutagen. A vicinal hydroxyl therefore does not interfere significantly with enzymatic epoxide hydrolysis, but it does enhance the bioalkylating potential of even an aliphatic epoxide.