G. Schroepfer
Jun 1, 1961
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0
Influential Citations
23
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Journal
The Journal of biological chemistry
Abstract
The conversion of lanosterol to cholesterol requires the removal of three methyl groups, reduction of the AX double bond, and “shift” of the nuclear double bond from position A* to position As. The mechanisms by which these changes occur and the sequence in which they occur are poorly understood at this time. The finding that Waring Blendor homogenates of rat liver are capable of efficiently converting zymosterol (As*24-cholestadienol), but not zymostenol (A*-cholestenol), to cholesterol (2) suggests that reduction of the A24 double bond of cholesterol precursors is probably a very late step in the formation of cholesterol (2-4). This view is strengthened by the isolation of desmosterol (A5,24cholestadienol) from chick embryos and rat liver and skin (4-6) and the demonstration of the conversion of this sterol to cholesterol in the rat (5). It has also been suggested, however, that reduction of the A24 double bond may occur relatively early in the reactions leading to the formation of cholesterol (7, 8). The present study concerns some further observations on the convertibility of zymosterol and zymostenol to cholesterol in intact rats and rat liver homogenates. In both Bucher and Waring Blendor homogenates of rat liver, zymostenol was found to be more readily convertible to cholesterol than was zymosterol, under the conditions studied. Observations made in this study suggest that zymosterol or other A24-sterols are not significant intermediates in the conversion of zymostenol to cholesterol. The effect of triparanol, an inhibitor of cholesterol synthesis (9), on the conversions of zymosterol and zymostenol to cholesterol by the rat has also been studied.