TY - JOUR T1 - Mechanism of glutathione-dependent dechlorination of chloramphenicol and thiamphenicol by cytosol of rat liver. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 371 LP - 375 VL - 8 IS - 6 AU - J L Martin AU - B J Gross AU - P Morris AU - L R Pohl Y1 - 1980/11/01 UR - http://dmd.aspetjournals.org/content/8/6/371.abstract 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 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. ER -