Implication of Rifampicin-quinone in the Irreversible Binding of Rifampicin to Macromolecules
- 1 January 1976
- journal article
- research article
- Published by Taylor & Francis in Xenobiotica
- Vol. 6 (1), 21-32
- https://doi.org/10.3109/00498257609151608
Abstract
1. When [3H]rifampicin is incubated with rat liver microsomes or rat liver homogenate, minor amounts are bound irreversibly to protein. This effect does not depend on the presence of NAD, NADH, NADP or NADPH. 2. Rifampicin is autoxidized at physiological pH. The product of autoxida-tion, rifampicin-quinone, if incubated with albumin, shows a much greater irreversible binding to the protein than the parent compound rifampicin. Hence it is concluded that rifampicin may bind irreversibly to proteins in a non-enzymic reaction after autoxidation to rifampicin-quinone. 3. Rifampicin-quinone also binds irreversibly to RNA and poly-L-lysine, if incubated with these compounds. This suggests that free amino groups of protein or RNA are involved in the binding. 4. 48 h after dosage of [3H]rifampicin (33 mg/kg) to rats, 29.2 ±4.1 (S.D.) pmol are bound irreversibly to 1 mg liver RNA, 15.8 ±8.1 pmol to 1 mg liver protein and 5.0 ± 0.47 pmol to 1 mg protein in brain tissue. 5. Microsomal NADPH-cytochrome c reductase is able to reduce rifampicin-quinone to rifampicin. The Km of this reaction is 10- 4 M. Induction of the NADPH-cytochrome c reductase by pre-treatment of rats with 20 mg/kg rifampicin over 5 days results in a corresponding increase of rifampicin-quinone reduction. 6. These results suggest that microsomal NADPH-cytochrome c reductase prevents accumulation of higher amounts of possibly toxic rifampicin-quinone by reduction to rifampicin.This publication has 25 references indexed in Scilit:
- Nebenwirkungen von Rifampicin und ihre biochemischen GrundlagenDeutsche Medizinische Wochenschrift (1946), 1975
- Sensitivity to Rifampicin: Incidence, Mechanism, and PreventionBMJ, 1974
- Irreversile binding of ethynyl-estradiol metabolites to protein and nucleic acids as catalyzed by rat liver microsomes and mushroom tyrosinasJournal of Steroid Biochemistry, 1974
- Stoffwechsel von Östron in der Mikrosomenfraktion der RattenleberHoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1974
- Solubilisierung und Anreicherung der NADPH-Cytochrom-Reduktase aus Rattenleber-MikrosomenHoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1974
- Potentially Serious Side Effects of High-dose Twice-weekly RifampicinBMJ, 1971
- Metabolism and mechanism of action of oestrogens XII. Structure and mechanism of formation of water-soluble and protein-bound metabolites of oestrone in rat-liver microsomes in vitro and in vivoBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1969
- Rifampicin: A New Orally Active RifamycinChemotherapy, 1966
- Sedimentation characteristics of rapidly labelled RNA from HeLa cellsBiochemical and Biophysical Research Communications, 1962
- The microestimation of succinate and the extinction coefficient of cytochrome cBiochimica et Biophysica Acta, 1959