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

Research output: Contribution to journal › Article › peer-review

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 - 1980
Externally published	Yes

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",

language = "English (US)",

volume = "8",

pages = "371--375",

journal = "Drug Metabolism and Disposition",

issn = "0090-9556",

publisher = "American Society for Pharmacology and Experimental Therapeutics",

number = "6",

}

TY - JOUR

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

Y1 - 1980

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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M3 - Article

C2 - 6109602

AN - SCOPUS:0019205195

SN - 0090-9556

VL - 8

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EP - 375

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

IS - 6

ER -

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

Abstract

ASJC Scopus subject areas

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