Inhibitors of sterol synthesis. Characterization of side chain oxygenated derivatives formed upon incubation of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one with rat liver mitochondria.
3 beta-Hydroxy-5 alpha-cholest-8(14)-en-15-one, a potent inhibitor of sterol biosynthesis, was incubated with rat liver mitochondrial preparations in the presence of NADPH. The following four major products were isolated and characterized by nuclear magnetic resonance and mass spectrometry: (25R)- and (25S)-3 beta,26-dihydroxy-5 alpha-cholest-8(14)-en-15-one (4:1 ratio), 3 beta-hydroxy-15-oxo-5 alpha-cholest-8(14)-en-26-oic acid, and 3 beta,25-dihydroxy-5 alpha-cholest-8(14)-en-15-one. In addition, 3 alpha,26-dihydroxy-5 alpha-cholest-8(14)-en-15-one and 3 beta,24-dihydroxy-5 alpha-cholest-8(14)-en-15-one were identified as minor products by capillary gas chromatography-mass spectrometry.
Pyrek
J S
JS
Department of Biochemistry, Rice University, Houston, Texas 77251-1892.
Vermilion
J L
JL
Stephens
T W
TW
Wilson
W K
WK
Schroepfer
G J
GJ
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002782:Cholestenes / Q000378:metabolism*; D002783:Cholestenones / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008745:Methylation; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D015394:Molecular Structure; D009249:NADP / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet; D013261:Sterols / Q000096:biosynthesis*
D002782:Cholestenes; D002783:Cholestenones; D013261:Sterols; C015073:cholest-8(14)-en-3-ol-15-one; D009249:NADP