Alphatic 3,4-epoxyalcohols. Metabolism by epoxide hydrase and mutagenic activity

Biochim Biophys Acta. 1978 Dec 18;544(3):504-13. doi: 10.1016/0304-4165(78)90325-2.

Abstract

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.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Epoxide Hydrolases / metabolism*
  • Epoxy Compounds / metabolism*
  • Ethers, Cyclic / metabolism*
  • Hydrolysis
  • Male
  • Microsomes, Liver / enzymology*
  • Mutagens / metabolism*
  • Rabbits
  • Structure-Activity Relationship

Substances

  • Epoxy Compounds
  • Ethers, Cyclic
  • Mutagens
  • Epoxide Hydrolases