title: Role of the 8-double bond of lanosterol in the enzyme-substrate interaction of cytochrome P-450(14DM) (lanosterol 14 alpha-demethylase).
abstract: The role of the 8-double bond of lanosterol in the enzyme-substrate interaction of yeast cytochrome P-450(14DM) (lanosterol 14 alpha-demethylase) was studied by analyzing metabolism of 8-lanostene-3 beta,32-diol, 7-lanostene-3 beta,32-diol, 6-lanostene-3 beta,32-diol and lanostane-3 beta,32-diol by the cytochrome. 8-Lanostene-3 beta,32-diol was actively metabolized by cytochrome P-450(14DM) and converted to the 32-nor-14-unsaturated metabolite. 7-Lanostene-3 beta,32-diol was also metabolized by the cytochrome, but the rate of metabolism was low. However, the cytochrome failed to catalyze the conversion of 6-lanostene-3 beta,32-diol and lanostane-3 beta,32-diol to their 32-nor metabolites. Spectral analysis of the sterol-cytochrome complexes and kinetics of cytochrome P-450(14DM) reduction in the presence of the sterols indicated that 6-lanostene-3 beta,32-diol and lanostane-3 beta,32-diol could not interact with the substrate site of the cytochrome. These results revealed that the 8-double bond of lanosterol plays an important role in the enzyme-substrate interaction of cytochrome P-450(14DM).
authors.affiliation: Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Sonoda
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007810:Lanosterol / Q000378:metabolism*; D008958:Models, Molecular; D010088:Oxidoreductases / Q000378:metabolism*; D058886:Sterol 14-Demethylase
chemical_list: D007810:Lanosterol; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase