Nadph Dependent Cytochrome P-450 Reactions- Mode Of Inhibition By The N—Butanol Fraction Of Desmodium Adscendens

Abstract

The n-butanol fraction (nBF) of Desrrodlvm a d scen d en s , a plant used for the management of asthma, is' an inhibitor of NADFH-dependent cytochrorre P-450 (CYP) reactions. Its mechanism of action as an inhibitor is hcwever not kncwn. In this study, flavoprotein reductase activity, spectral changes associated with binding and spectral properties of reduced cytochrcme c and CYP were used to investigate the mode of inhibition. nBF reduced cytochrane c but not CYP directly. In the presence of NADFH, the rate of formation of CYP2* (the reduced form of CYP) v\as enhanced ty the addition of nBF. These effects were observed in reactions without substrate, indicating that in the absence of a substrate, nBF does noc prevent the NADPH reduction of CYP, but rather enhances it. In the presence of a substrate, as exemplified ty a spectrophotometric assay of the ERCD reaction, nBF v*as found to change the spectrum of oxidized CYP. The results indicate that in the presence of nBF, the binding site of CYP is altered to prevent substrate binding.