Differential substrate selectivity of murine hepatic cytosolic and microsomal epoxide hydrolases

Bruce D. Hammock, Leslie S. Hasagawa

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The initial rates of hydration of sixteen epoxides in the presence of cytosolic and microsomal fractions of mouse liver were determined. 1,2-Disubstituted trans-epoxides were found to be excellent, selective substrates for the cytosolic epoxide hydrolase, while 1,2-cis-epoxides were poorly hydrated when one or more substituents was a phenyl moiety. Epoxides of cyclic systems including benzo[a]pyrene 4,5-oxide, and two cyclodiene analogs were hydrated almost exclusively by the microsomal epoxide hydrolase while monosubstituted epoxides were hydrated by both systems. Some epoxides which were mediocre substrates proved to be reasonable inhibitors of the cytosolic epoxide hydrolase, indicating that the structural requirements for substrate binding and turnover are different. Some reagents known to interact with sulfhydryl groups, including styrene oxide, proved to be good inhibitors. This work facilitates the design of radiochemical and spectrophotometric assays for both major forms of epoxide hydrolase as well as prediction of potential intrinsic substrates. Also such data may be meaningful in assessing the risk involved in human exposure to epoxidized xenobiotics.

Original languageEnglish (US)
Pages (from-to)1155-1164
Number of pages10
JournalBiochemical Pharmacology
Volume32
Issue number7
DOIs
StatePublished - Apr 1 1983

Fingerprint

Epoxide Hydrolases
Epoxy Compounds
Liver
Substrates
styrene oxide
Xenobiotics
Hydration
Assays

ASJC Scopus subject areas

  • Pharmacology

Cite this

Differential substrate selectivity of murine hepatic cytosolic and microsomal epoxide hydrolases. / Hammock, Bruce D.; Hasagawa, Leslie S.

In: Biochemical Pharmacology, Vol. 32, No. 7, 01.04.1983, p. 1155-1164.

Research output: Contribution to journalArticle

Hammock, Bruce D. ; Hasagawa, Leslie S. / Differential substrate selectivity of murine hepatic cytosolic and microsomal epoxide hydrolases. In: Biochemical Pharmacology. 1983 ; Vol. 32, No. 7. pp. 1155-1164.
@article{42ef7923394c43f98ca61fb9720fb5a5,
title = "Differential substrate selectivity of murine hepatic cytosolic and microsomal epoxide hydrolases",
abstract = "The initial rates of hydration of sixteen epoxides in the presence of cytosolic and microsomal fractions of mouse liver were determined. 1,2-Disubstituted trans-epoxides were found to be excellent, selective substrates for the cytosolic epoxide hydrolase, while 1,2-cis-epoxides were poorly hydrated when one or more substituents was a phenyl moiety. Epoxides of cyclic systems including benzo[a]pyrene 4,5-oxide, and two cyclodiene analogs were hydrated almost exclusively by the microsomal epoxide hydrolase while monosubstituted epoxides were hydrated by both systems. Some epoxides which were mediocre substrates proved to be reasonable inhibitors of the cytosolic epoxide hydrolase, indicating that the structural requirements for substrate binding and turnover are different. Some reagents known to interact with sulfhydryl groups, including styrene oxide, proved to be good inhibitors. This work facilitates the design of radiochemical and spectrophotometric assays for both major forms of epoxide hydrolase as well as prediction of potential intrinsic substrates. Also such data may be meaningful in assessing the risk involved in human exposure to epoxidized xenobiotics.",
author = "Hammock, {Bruce D.} and Hasagawa, {Leslie S.}",
year = "1983",
month = "4",
day = "1",
doi = "10.1016/0006-2952(83)90264-2",
language = "English (US)",
volume = "32",
pages = "1155--1164",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "7",

}

TY - JOUR

T1 - Differential substrate selectivity of murine hepatic cytosolic and microsomal epoxide hydrolases

AU - Hammock, Bruce D.

AU - Hasagawa, Leslie S.

PY - 1983/4/1

Y1 - 1983/4/1

N2 - The initial rates of hydration of sixteen epoxides in the presence of cytosolic and microsomal fractions of mouse liver were determined. 1,2-Disubstituted trans-epoxides were found to be excellent, selective substrates for the cytosolic epoxide hydrolase, while 1,2-cis-epoxides were poorly hydrated when one or more substituents was a phenyl moiety. Epoxides of cyclic systems including benzo[a]pyrene 4,5-oxide, and two cyclodiene analogs were hydrated almost exclusively by the microsomal epoxide hydrolase while monosubstituted epoxides were hydrated by both systems. Some epoxides which were mediocre substrates proved to be reasonable inhibitors of the cytosolic epoxide hydrolase, indicating that the structural requirements for substrate binding and turnover are different. Some reagents known to interact with sulfhydryl groups, including styrene oxide, proved to be good inhibitors. This work facilitates the design of radiochemical and spectrophotometric assays for both major forms of epoxide hydrolase as well as prediction of potential intrinsic substrates. Also such data may be meaningful in assessing the risk involved in human exposure to epoxidized xenobiotics.

AB - The initial rates of hydration of sixteen epoxides in the presence of cytosolic and microsomal fractions of mouse liver were determined. 1,2-Disubstituted trans-epoxides were found to be excellent, selective substrates for the cytosolic epoxide hydrolase, while 1,2-cis-epoxides were poorly hydrated when one or more substituents was a phenyl moiety. Epoxides of cyclic systems including benzo[a]pyrene 4,5-oxide, and two cyclodiene analogs were hydrated almost exclusively by the microsomal epoxide hydrolase while monosubstituted epoxides were hydrated by both systems. Some epoxides which were mediocre substrates proved to be reasonable inhibitors of the cytosolic epoxide hydrolase, indicating that the structural requirements for substrate binding and turnover are different. Some reagents known to interact with sulfhydryl groups, including styrene oxide, proved to be good inhibitors. This work facilitates the design of radiochemical and spectrophotometric assays for both major forms of epoxide hydrolase as well as prediction of potential intrinsic substrates. Also such data may be meaningful in assessing the risk involved in human exposure to epoxidized xenobiotics.

UR - http://www.scopus.com/inward/record.url?scp=0020540930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020540930&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(83)90264-2

DO - 10.1016/0006-2952(83)90264-2

M3 - Article

C2 - 6847708

AN - SCOPUS:0020540930

VL - 32

SP - 1155

EP - 1164

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 7

ER -