Cholesterol Biosynthesis in Preparations of Liver from Normal, Fasting, X-irradiated, Cholesterol-fed, Triton, or Δ4-Cholesten-3-one-treated Rats

Abstract

The biosynthesis of cholesterol from acetate in rat liver is greatly augmented by exposure of the animal to x-irradiation (l-4), or by injection of the detergent Triton WR 1339 (Rohm and Haas) (5). On the other hand, it is suppressed in animals deprived of food for 24 to 48 hours (6, 7) or fed a cholesterolenriched diet (8-12) or A4-cholestenone (13, 14). These findings are mainly based upon experiments carried out in the whole animal or in liver slices in vitro. The present study is concerned with the relation of these various experimental conditions to the capacity of cell-free preparations of rat liver to synthesize cholesterol from acetate-U4, mevalonic acid-CY4, and squalene-Cr4, and to synthesize squalene from acetate-C14. The aim has been to find whether the differences demonstrable with the complete system (acetate to cholesterol) involved the whole reaction chain or were limited to specific segments of the biosynthetic pathway, and also to learn whether a common pattern of changes would emerge under these diverse experimental conditions. Previous work, as well as data to be presented below, has shown that the cholesterolsynthesizing system requires both the microsomes and soluble cell components (15). These cellular constituents were accordingly separated from livers of different experimental groups and recombined in various ways, in order to determine to what extent the structural elements of the system were altered. In all of the experimental conditions tested, the microsomal rather than the soluble parts of the system were chiefly affected, although the latter too reflected the change. Further, the early steps in the reaction sequence were influenced to a far greater extent than the later ones.