Mechanism of glutathione-dependent dechlorination of chloramphenicol and thiamphenicol by cytosol of rat liver

J. L. Martin; B. J. Gross; P. Morris; L. R. Pohl

Mechanism of glutathione-dependent dechlorination of chloramphenicol and thiamphenicol by cytosol of rat liver

J. L. Martin, B. J. Gross, P. Morris, L. R. Pohl

School of Medicine

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12 Scopus citations

Abstract

Chloramphenicol (CAP, RNHCOCHCl₂) has previously been shown to be dechlorinated to CAP aldehyde (RNHCOCHO) and CAP oxamic acid (RNHCOCO₂H) by rat liver cytosol. In the present study we have further characterized these reactions and have found that several homogeneous rat liver GSH transferases, particularly transferase A, metabolize CAP to CAP aldehyde by an apparent hydrolytic dechlorination mechanism. The aldehyde is further metabolized to CAP oxamic acid by an aldehyde oxidizing enzyme(s) which does not require GSH, but can utilize either NAD⁺ or NADP⁺. Thiamphenicol, the p-methylsulfonylphenyl derivative of CAP, also appears to be metabolized through these pathways, but to a lesser extent than is CAP.

Original language	English (US)
Pages (from-to)	371-375
Number of pages	5
Journal	Drug Metabolism and Disposition
Volume	8
Issue number	6
State	Published - Dec 1 1980

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science

Cite this

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title = "Mechanism of glutathione-dependent dechlorination of chloramphenicol and thiamphenicol by cytosol of rat liver",

abstract = "Chloramphenicol (CAP, RNHCOCHCl2) has previously been shown to be dechlorinated to CAP aldehyde (RNHCOCHO) and CAP oxamic acid (RNHCOCO2H) by rat liver cytosol. In the present study we have further characterized these reactions and have found that several homogeneous rat liver GSH transferases, particularly transferase A, metabolize CAP to CAP aldehyde by an apparent hydrolytic dechlorination mechanism. The aldehyde is further metabolized to CAP oxamic acid by an aldehyde oxidizing enzyme(s) which does not require GSH, but can utilize either NAD+ or NADP+. Thiamphenicol, the p-methylsulfonylphenyl derivative of CAP, also appears to be metabolized through these pathways, but to a lesser extent than is CAP.",

author = "Martin, {J. L.} and Gross, {B. J.} and P. Morris and Pohl, {L. R.}",

year = "1980",

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T1 - Mechanism of glutathione-dependent dechlorination of chloramphenicol and thiamphenicol by cytosol of rat liver

AU - Martin, J. L.

AU - Gross, B. J.

AU - Morris, P.

AU - Pohl, L. R.

PY - 1980/12/1

Y1 - 1980/12/1

N2 - Chloramphenicol (CAP, RNHCOCHCl2) has previously been shown to be dechlorinated to CAP aldehyde (RNHCOCHO) and CAP oxamic acid (RNHCOCO2H) by rat liver cytosol. In the present study we have further characterized these reactions and have found that several homogeneous rat liver GSH transferases, particularly transferase A, metabolize CAP to CAP aldehyde by an apparent hydrolytic dechlorination mechanism. The aldehyde is further metabolized to CAP oxamic acid by an aldehyde oxidizing enzyme(s) which does not require GSH, but can utilize either NAD+ or NADP+. Thiamphenicol, the p-methylsulfonylphenyl derivative of CAP, also appears to be metabolized through these pathways, but to a lesser extent than is CAP.

AB - Chloramphenicol (CAP, RNHCOCHCl2) has previously been shown to be dechlorinated to CAP aldehyde (RNHCOCHO) and CAP oxamic acid (RNHCOCO2H) by rat liver cytosol. In the present study we have further characterized these reactions and have found that several homogeneous rat liver GSH transferases, particularly transferase A, metabolize CAP to CAP aldehyde by an apparent hydrolytic dechlorination mechanism. The aldehyde is further metabolized to CAP oxamic acid by an aldehyde oxidizing enzyme(s) which does not require GSH, but can utilize either NAD+ or NADP+. Thiamphenicol, the p-methylsulfonylphenyl derivative of CAP, also appears to be metabolized through these pathways, but to a lesser extent than is CAP.

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ER -

Mechanism of glutathione-dependent dechlorination of chloramphenicol and thiamphenicol by cytosol of rat liver

Abstract

ASJC Scopus subject areas

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