title: Stereoselective inhibition of cholesterol side chain cleavage by enantiomers of aminoglutethimide.
abstract: Because aminoglutethimide is a potentially important drug in the treatment of certain maligancies as well as fertility control, its stereoisomers were studied for binding to corpus luteum mitochondrial cytochrome P-450 and inhibition of cholesterol side chain cleavage. The binding affinity, determined from induced spectral changes, is 2.6 times greater for the d- than for the l-isomer. In the enzyme assay, the d-isomer is 2.5 times more potent as an inhibitor of cholesterol side chain cleavage than is the l-isomer. The extent of inhibition and the change in the absorptivity of the P-450-inhibitor complex are linearly related for both chiral and racemic forms. Thus, the active center of the enzyme is stereoselective for the enantiomers of aminoglutethimide.
mesh_terms: D000616:Aminoglutethimide / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors*; D003338:Corpus Luteum / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D008928:Mitochondria / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D013053:Spectrophotometry; D013237:Stereoisomerism
chemical_list: D000616:Aminoglutethimide; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D002786:Cholesterol Side-Chain Cleavage Enzyme