Epoxidation of 2,3-oxidosqualene to 2,3;22,23-squalene dioxide by squalene epoxidase.
Partially purified squalene epoxidase (SE) from pig liver converts 2,3-oxidosqualene (SO) to 2,3;22,23-squalene dioxide (SDO) with approximately one-half the efficiency of the epoxidation of squalene at pH 7.4. The SO to SDO conversion is independent of pH and shows an absolute requirement for exogenous FAD. Two noncompetitive SE inhibitors show selectivity in blocking squalene (Sq) to SO versus SO to SDO epoxidations. Finally, SDO inhibits the activity of crude pig liver oxidosqualene cyclase (OSC) with an IC50 of 16 microM. Thus, SE inhibitors not only reduce the production of SO from Sq, but also strongly suppress "leakage" of SO to the potentially harmful SDO in vitro.
Bai
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Department of Chemistry, State University of New York, Stony Brook 11794-3400.
Xiao
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Prestwich
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D000818:Animals; D005182:Flavin-Adenine Dinucleotide / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D010105:Oxygenases / Q000187:drug effects / Q000378:metabolism*; D013185:Squalene / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D050603:Squalene Monooxygenase; D013552:Swine
C002821:2,3-oxidosqualene; C015171:2,3,22,23-dioxidosqualene; D005182:Flavin-Adenine Dinucleotide; D013185:Squalene; D010105:Oxygenases; D050603:Squalene Monooxygenase