Mechanism of glutathione-dependent dechlorination of chloramphenicol and thiamphenicol by cytosol of rat liver.
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 transferases 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.
D000818:Animals; D002701:Chloramphenicol / Q000031:analogs & derivatives / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology*; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D013839:Thiamphenicol / Q000378:metabolism*
D002701:Chloramphenicol; C028709:chloramphenicol aldehyde; C027241:chloramphenicol oxamic acid; D005982:Glutathione Transferase; D013839:Thiamphenicol