Abstract
Incubation with chloramphenicol in the presence of NADPH leads to the irreversible inhibition of the 7-ethoxycoumarin deethylase and benzphetamine demethylase activities of the cytochrome P-450 of a reconstituted monooxygenase system purified from liver microsomes of phenobarbital-treated rats. The inactivation is accompanied by the covalent binding of 1.5 nmol 14C from [1,2-14C]chloramphenicol per nmol cytochrome P-450 but not by a decrease in cytochrome P-450 detectable as its carbon monoxide complex or by a decrease in heme detectable as pyridine hemachromagen. The data suggest that chloramphenicol acts as a suicide substrate of cytochrome P-450 and may prove to be a valuable tool for identifying amino acid residues at or near the active site of the enzyme.
- Copyright © 1980 by The American Society for Pharmacology and Experimental Therapeutics
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