Substrate selectivity and stereochemistry of enzymatic epoxide hydration in the soluble fraction of mouse liver

Susanne M. Mumby, Bruce D. Hammock

Research output: Contribution to journalArticle

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Abstract

The relative rates and geometry of hydration of several substrates and other properties of a 100,000g soluble subcellular fraction epoxide hydrase(s) from mouse liver were examined. Mono-, di-, tri-, and tetrasubstituted alkyl epoxides which are insect juvenile hormone mimics are rapidly hydrated in the soluble fraction. For the trisubstituted epoxides the rate of hydration decreases as one of the alkyl chains is lengthened while the opposite trend is observed with most disubstituted epoxides. For the compounds examined the initial rate of hydration of alkyl-substituted epoxides by the soluble fraction is cis-di- {greater-than or less-than} mono- ≥ trans-di- > tri- > tetrasubstituted. Two trisubstituted, a disubstituted, and a monosubstituted epoxide are rapidly hydrated by a single peak of enzyme activity from a gel filtration column. cis-Disubstituted epoxides are hydrated stereospecifically to their threo-diols and trans-epoxides to their erythro-diols, indicating trans-opening of the oxirane ring. Trisubstituted epoxides inhibit the hydration of di- and monosubstituted epoxides and trans- disubstituted epoxides inhibit the hydration of cis-disubstituted epoxides. The apparent Km and Vmax for one trisubstituted epoxide compare favorably with those reported for a number of substrates hydrated by the microsomal epoxide hydrase(s). Epoxide hydrase activity in the soluble and other subcellular fractions should thus be considered when examining the role of mammalian epoxide hydrases.

Original languageEnglish (US)
Pages (from-to)275-284
Number of pages10
JournalPesticide Biochemistry and Physiology
Volume11
Issue number1-3
DOIs
StatePublished - 1979

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Stereochemistry
Epoxy Compounds
stereochemistry
epoxides
Hydration
Liver
liver
mice
Substrates
Epoxide Hydrolases
Subcellular Fractions
subcellular fractions
glycols
Insect Hormones
Juvenile Hormones
Ethylene Oxide
Enzyme activity
insect hormones
ethylene oxide
Gel Chromatography

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Biochemistry
  • Physiology

Cite this

Substrate selectivity and stereochemistry of enzymatic epoxide hydration in the soluble fraction of mouse liver. / Mumby, Susanne M.; Hammock, Bruce D.

In: Pesticide Biochemistry and Physiology, Vol. 11, No. 1-3, 1979, p. 275-284.

Research output: Contribution to journalArticle

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