The interaction of cytosolic epoxide hydrolase with chiral epoxides

Eric C. Dietze, Eiichi Kuwano, Bruce D. Hammock

Research output: Contribution to journalArticle

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Abstract

1. 1. The kinetic parameters of the cytosolic epoxide hydrolase were examined with two sets of spectrophotometric substrates. The (2S,3S)- and (2R,3R)-enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-phenylpropyl carbonate had a Kmof 33 and 68 μm and a Vmax of 16 and 27 μmol/min/mg, respectively. With the (2S,3S)- and (2R,3R)- enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate, cytosolic epoxide hydrolase had a KM of 8.0 and 15 μM and a Vmax of 7.8 and 5.0 μmol/min/mg, respectively. 2. 2. Glycidyl 4-nitrobenzoate had the lowest I50 of the compounds tested in the glycidyl 4-nitrobenzoate series (I50= 140 μM). The I50 of the (2R)-enantiomer was 3.7-fold higher. The inhibitor with the lowest i50 in the glycidol series, and the lowest I50 of any compound tested, was (2S,3S)-3-(4-nitrophenyl)glycidol (I50 = 13.0μM). It also showed the greatest difference in I50 between the enantiomers (330-fold). 3. 3. All enantiomers of glycidyl 4-nitrobenzoates and trans-3-phenylglycidols gave differential inhibition of cytosolic epoxide hydrolase. However, neither the (S,S)-/(S)- or (R,R)-/(R)-enantiomer always had the lower I50. 4. 4. Addition of one or more methyl groups to either enantiomer of glycidyl 4-nitrobenzoate resulted in increased I50. However, addition of a methyl group to C2 of either enantiomer of 3-phenylglycidol resulted in a decreased I50. Finally, when the hydroxyl group of trans-3-(4-nitrophenyl)glycidol was esterified the I50 of the (2S,3S)- but not the (2R,3R)-enantiomer increased.

Original languageEnglish (US)
Pages (from-to)43-52
Number of pages10
JournalInternational Journal of Biochemistry
Volume25
Issue number1
DOIs
StatePublished - 1993

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glycidol
Epoxide Hydrolases
Enantiomers
Epoxy Compounds
Carbonates
Hydroxyl Radical
4-nitrophenyl
glycidyl 4-nitrobenzoate
Kinetic parameters

ASJC Scopus subject areas

  • Biochemistry

Cite this

The interaction of cytosolic epoxide hydrolase with chiral epoxides. / Dietze, Eric C.; Kuwano, Eiichi; Hammock, Bruce D.

In: International Journal of Biochemistry, Vol. 25, No. 1, 1993, p. 43-52.

Research output: Contribution to journalArticle

Dietze, Eric C. ; Kuwano, Eiichi ; Hammock, Bruce D. / The interaction of cytosolic epoxide hydrolase with chiral epoxides. In: International Journal of Biochemistry. 1993 ; Vol. 25, No. 1. pp. 43-52.
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abstract = "1. 1. The kinetic parameters of the cytosolic epoxide hydrolase were examined with two sets of spectrophotometric substrates. The (2S,3S)- and (2R,3R)-enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-phenylpropyl carbonate had a Kmof 33 and 68 μm and a Vmax of 16 and 27 μmol/min/mg, respectively. With the (2S,3S)- and (2R,3R)- enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate, cytosolic epoxide hydrolase had a KM of 8.0 and 15 μM and a Vmax of 7.8 and 5.0 μmol/min/mg, respectively. 2. 2. Glycidyl 4-nitrobenzoate had the lowest I50 of the compounds tested in the glycidyl 4-nitrobenzoate series (I50= 140 μM). The I50 of the (2R)-enantiomer was 3.7-fold higher. The inhibitor with the lowest i50 in the glycidol series, and the lowest I50 of any compound tested, was (2S,3S)-3-(4-nitrophenyl)glycidol (I50 = 13.0μM). It also showed the greatest difference in I50 between the enantiomers (330-fold). 3. 3. All enantiomers of glycidyl 4-nitrobenzoates and trans-3-phenylglycidols gave differential inhibition of cytosolic epoxide hydrolase. However, neither the (S,S)-/(S)- or (R,R)-/(R)-enantiomer always had the lower I50. 4. 4. Addition of one or more methyl groups to either enantiomer of glycidyl 4-nitrobenzoate resulted in increased I50. However, addition of a methyl group to C2 of either enantiomer of 3-phenylglycidol resulted in a decreased I50. Finally, when the hydroxyl group of trans-3-(4-nitrophenyl)glycidol was esterified the I50 of the (2S,3S)- but not the (2R,3R)-enantiomer increased.",
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N2 - 1. 1. The kinetic parameters of the cytosolic epoxide hydrolase were examined with two sets of spectrophotometric substrates. The (2S,3S)- and (2R,3R)-enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-phenylpropyl carbonate had a Kmof 33 and 68 μm and a Vmax of 16 and 27 μmol/min/mg, respectively. With the (2S,3S)- and (2R,3R)- enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate, cytosolic epoxide hydrolase had a KM of 8.0 and 15 μM and a Vmax of 7.8 and 5.0 μmol/min/mg, respectively. 2. 2. Glycidyl 4-nitrobenzoate had the lowest I50 of the compounds tested in the glycidyl 4-nitrobenzoate series (I50= 140 μM). The I50 of the (2R)-enantiomer was 3.7-fold higher. The inhibitor with the lowest i50 in the glycidol series, and the lowest I50 of any compound tested, was (2S,3S)-3-(4-nitrophenyl)glycidol (I50 = 13.0μM). It also showed the greatest difference in I50 between the enantiomers (330-fold). 3. 3. All enantiomers of glycidyl 4-nitrobenzoates and trans-3-phenylglycidols gave differential inhibition of cytosolic epoxide hydrolase. However, neither the (S,S)-/(S)- or (R,R)-/(R)-enantiomer always had the lower I50. 4. 4. Addition of one or more methyl groups to either enantiomer of glycidyl 4-nitrobenzoate resulted in increased I50. However, addition of a methyl group to C2 of either enantiomer of 3-phenylglycidol resulted in a decreased I50. Finally, when the hydroxyl group of trans-3-(4-nitrophenyl)glycidol was esterified the I50 of the (2S,3S)- but not the (2R,3R)-enantiomer increased.

AB - 1. 1. The kinetic parameters of the cytosolic epoxide hydrolase were examined with two sets of spectrophotometric substrates. The (2S,3S)- and (2R,3R)-enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-phenylpropyl carbonate had a Kmof 33 and 68 μm and a Vmax of 16 and 27 μmol/min/mg, respectively. With the (2S,3S)- and (2R,3R)- enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate, cytosolic epoxide hydrolase had a KM of 8.0 and 15 μM and a Vmax of 7.8 and 5.0 μmol/min/mg, respectively. 2. 2. Glycidyl 4-nitrobenzoate had the lowest I50 of the compounds tested in the glycidyl 4-nitrobenzoate series (I50= 140 μM). The I50 of the (2R)-enantiomer was 3.7-fold higher. The inhibitor with the lowest i50 in the glycidol series, and the lowest I50 of any compound tested, was (2S,3S)-3-(4-nitrophenyl)glycidol (I50 = 13.0μM). It also showed the greatest difference in I50 between the enantiomers (330-fold). 3. 3. All enantiomers of glycidyl 4-nitrobenzoates and trans-3-phenylglycidols gave differential inhibition of cytosolic epoxide hydrolase. However, neither the (S,S)-/(S)- or (R,R)-/(R)-enantiomer always had the lower I50. 4. 4. Addition of one or more methyl groups to either enantiomer of glycidyl 4-nitrobenzoate resulted in increased I50. However, addition of a methyl group to C2 of either enantiomer of 3-phenylglycidol resulted in a decreased I50. Finally, when the hydroxyl group of trans-3-(4-nitrophenyl)glycidol was esterified the I50 of the (2S,3S)- but not the (2R,3R)-enantiomer increased.

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