Calculation of competitive inhibition of substrate binding to cytochrome P-450 illustrated by the interaction of d,l-propranolol with d,l-hexobarbital.
Various forms of cytochrome P-450 exist. A substrate may bind to these forms completely or partially. In addition, during the interaction of two substrates, several cytochrome P-450 forms may also be involved, either partially or completely. Now a method is described which allows the estimation of the spectral dissociation constants for the binding of two compounds to cytochrome P-450 subforms common to both. The method is illustrated by the competitive interaction of d,l-hexobarbital and d,l-propranolol with cytochrome P-450 which show only a partial overlap for type I binding sites using rat hepatic microsomes. Different subforms of cytochrome P-450 may be characterized by means of crossover studies with several type I compounds using this method.
Department of Pharmacology, Medical Faculty, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
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Bast
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Noordhoek
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006591:Hexobarbital / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011433:Propranolol / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D013379:Substrate Specificity
D003577:Cytochrome P-450 Enzyme System; D011433:Propranolol; D006591:Hexobarbital