RT Journal Article
SR Electronic
T1 Mechanism of glutathione-dependent dechlorination of chloramphenicol and thiamphenicol by cytosol of rat liver.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 371
OP 375
VO 8
IS 6
A1 J L Martin
A1 B J Gross
A1 P Morris
A1 L R Pohl
YR 1980
UL http://dmd.aspetjournals.org/content/8/6/371.abstract
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 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.