I 



BIOSYNTHESIS OF CHOLESTEROL 381 



in which acetate containing isotopic carbon was used, it was found that 

 both carbons of acetic acid are used for cholesterol synthesis; at least one- 

 half of the cholesterol was shown to be derived from acetate. 



Not only has the synthesis of cholesterol been demonstrated in the intact 

 animal, but it has been shown to occur in liver slices an in other tissues in 

 vitro. Thus, Bloch, Borek, and Rittenberg^^^ observed that slices of rat 

 liver were able to synthesize cholesterol from isotopic acetate under aerobic 

 but not under anaerobic conditions. Ponticorvo et al^^° reported that, 

 when deuterium-labeled sodium acetate was fed to growing rats, the fatty 

 acids contained 20% and the cholesterol 45% of the carbon atoms of the 

 acetate. In a later study to determine the rate of synthesis of fatty acids 

 and of cholesterol from acetate in the adult rat, Pihl, Bloch, and Anker'**^ 

 calculated the half-times of saturated and of unsaturated acids in the liver 

 as one and two days, respectively, while that of cholesterol in this organ 

 was estimated as six days. The corresponding half-times in the carcass 

 were sixteen to seventeen days (saturated acids), nineteen to twenty days 

 (unsaturated acids), and thirty-one to thirty-two days (cholesterol). 

 Brady and Gurin^^^ confirmed the synthesis of cholesterol by the liver 

 slices of rats from acetic, pyruvic, hexanoic, and octanoic acids. 



Although liver homogenates were believed to be an unsatisfactory me- 

 dium for cholesterol synthesis, Rabinowitz and Greenberg^** reported that at 

 least part of the synthesis of cholesterol from acetate can be effected by a 

 broken cell preparation of fetal rat liver. More recently, Frantz and 

 Bucher^*^ proved the identity of cholesterol sjmthesized by homogenates of 

 ordinary rat liver; these workers based their conclusions as to radiochemi- 

 cal identity and purity upon fractional crystallization, formation of the 

 dibromide, acetylation and solubility reactions. Although C ^^-choles- 

 terol obtained by perfusion of livers and of other organs of swine with 

 carboxyl-labeled sodium acetate contains substances having a higher 

 specific count than that of C''*-cholesterol, the substance could be con- 

 verted via 5,G-dibromo-3-cholesterol into C^^-cholesterol with a constant 

 specific count. ^^^ Schwenk and Baker^*^ likewise demonstrated the pres- 

 ence in the hen of substances having a higher count than that of the C^^- 



1" K. Bloch, E. Borek, and D. Rittenberg, J. Biol. Chem., 162, 441-449 (1946). 



ISO L. Ponticorvo, D. Rittenberg, and K. Bloch, /. Biol. Chem., 179, 839-842 (1949). 



181 A. Pihl, K. Bloch, and H. S. Anker, J. Biol. Chem., 183, 441-450 (1950). 



182 R. O. Brady and S. Gurin, /. Biol. Chem., 186, 461-469 ( 1950). 



183 M. Rabinowitz and D. M. Greenberg, Arch. Biochem. Biophys., 40, 472-474 (1952). 



184 I. D. Frantz, Jr., and N. L. R. Bucher, /. Biol. Chem., 206, 471-481 (1954). 



185 E. Schwenk and N. T Werthessen, Arch. Biochem. Biophys., 40, 334-341 (1952). 

 188 E Schwenk and C F Baker, Arch. Biochem. Biophys., 45, 341-348 (1953). 



