Martin J L, Gross B J, Morris P, Pohl L R
Drug Metab Dispos. 1980 Nov-Dec;8(6):371-5.
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.
氯霉素(CAP,RNHCOCHCl₂)先前已被证明可被大鼠肝细胞溶胶脱氯生成氯霉素醛(RNHCOCHO)和氯霉素草氨酸(RNHCOCO₂H)。在本研究中,我们进一步对这些反应进行了表征,发现几种纯的大鼠肝脏谷胱甘肽转移酶,特别是转移酶A,通过一种明显的水解脱氯机制将CAP代谢为氯霉素醛。该醛进一步被一种醛氧化酶代谢为氯霉素草氨酸,该醛氧化酶不需要谷胱甘肽,但可以利用NAD⁺或NADP⁺。甲砜霉素,CAP的对甲基磺酰苯基衍生物,似乎也通过这些途径代谢,但程度比CAP小。