Preferential cyclization of 2,3(S):22(S),23-dioxidosqualene by mammalian 2,3-oxidosqualene-lanosterol cyclase.
Kinetic studies on the cyclization of 2,3(S)-oxido and 2,3(S):22(S),23-dioxido[14C]squalene catalyzed by liver oxidosqualene-lanosterol cyclase revealed a specificity (in terms of V/Km) of the enzyme for the diepoxide. The specificity ratio was dependent on the enzyme preparation, i.e. purified or microsomal, and was highest (about 5) with the microsomal enzyme in the presence of supernatant protein factors. These results explain why, in the presence of cyclase inhibitors, the squalene epoxides can be channeled into a cholesterol biosynthesis regulatory pathway via 24(S),25-epoxylanosterol and 24(S),25-epoxycholesterol.
Boutaud
O
O
Laboratoire de Chimie Bioorganique (CNRS URA-1386), Faculté de Pharmacie, Illkirch, France.
Dolis
D
D
Schuber
F
F
D016475:3T3 Cells; D000818:Animals; D002250:Carbon Radioisotopes; D008401:Gas Chromatography-Mass Spectrometry; D019751:Intramolecular Transferases; D007535:Isomerases / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D013185:Squalene / Q000031:analogs & derivatives* / Q000378:metabolism; D013379:Substrate Specificity; D014316:Tritium
D002250:Carbon Radioisotopes; D014316:Tritium; C015171:2,3,22,23-dioxidosqualene; D013185:Squalene; D007535:Isomerases; D019751:Intramolecular Transferases; C021924:lanosterol synthase