BIOSYNTHESIS OF CHOLESTEROL 393 



considered that the total fat content of the diet was more important in de- 

 termining the serum cholesterol level than was the amount of cholesterol 

 itself ingested. 



f. The Effect of Soy Sterols. Although the effect of soy sterols in pre- 

 venting the accumulation of cholesterol in the liver and tissues is largely a 

 result of the blocking of cholesterol absorption in the intestine, it is of 

 interest to determine whether or not a phenomenon of this nature alters 

 the rate of cholesterol synthesis in the tissues. This question has been 

 answered in the negative by Alfin -Slater and co-workers, ^''^ who reported 

 that the rate of synthesis of endogenous cholesterol was not affected when 

 the doses of soy sterols were sufficient to prevent any appreciable amount of 

 cholesterol from being absorbed. 



g. The Effect of Cations and of Hydrogen-Ion Concentration. Cur- 

 ran^*'^ reported that the optimum rate of cholesterol synthesis in surviving 

 rat liver in vitro occurs between a pH of 6.2 and one of 6.8, although ac- 

 tivity was noted in the range of 6.0 to 7.4. The effect of pH on the rate 

 of cholesterol synthesis persists in the absence of potassium and magnesium 

 ions, and is independent of the loss of intracellular potassium. -^^ This 

 finding is somewhat unexpected, since sufficient K+ and Mg++ must be 

 present in the incubating medium if marked variations in the rate of choles- 

 terol synthesis are to be avoided. The effectiveness of the acetate — > 

 cholesterol reaction at a pH of 6.5 is augmented by the presence of Mn++; 

 this effect occurs even if Mg++ is present at an optimum leveL^"*^ Bucher 

 et al.'^'^^ reported that the omission of MgCl2 and DPN from the incubation 

 mixture of cell-free homogenates of adult rat liver reduced the synthetic 

 capacity for cholesterol. For a more complete discussion of the effect of 

 cholesterol analogues on the absorption process, the reader is referred to 

 The Lipids, Vol. II, pages 270-271, and page 364 of the present volume. 



h. The Effect of Hormones. The synthesis of cholesterol is stimu- 

 lated in hyperthyroid states, and is decreased when a hypothyroid condition 

 obtains. 2*''' 2" Marx and co-workers^?^ confirmed these findings and re- 



2« R. B. Alfin-Slater, A. F. Wells, L. Aftergood, and H. J. Deuel, Jr., Unpublished 

 observations, 1955. 



2« G. L. Curran, /. Biol. Chem., 200, 17-21 (1953). 



2« G. L. Currau and O. L. Clute, J. Biol. Chem., S04, 215-219 (1953). 



"9 N. L. R. Bucher, N. H. McGovern, R. Kingston, and M. H. Kennedy, Federation 

 Proc, 12, 184 (1953). 



^o R. H. Rosenman, S. O. Byers, and M. Friedman, J. Clin. Endocrinol, and Metabo- 

 lism, 12, 1287-1299 (1952). 



251 S. O. Byers, R. H. Rosenman, M. Friedman, and M. W. Biggs, J. Exptl. Med., 96, 

 513-516(1952). 



«2 W. Marx, S. T. Gustin, and C. Levi, Proc. Soc. Exptl. Biol. Med., 83, 143-146 

 (1953). 



