406 VIII. CHOLESTEROL AND RELATED STEROLS 



Apparently all bile acids originate, either directly or indirectly, from 

 cholesterol, but the preponderance of cholic acid in dog bile has made it 

 easier to isolate this acid. In the case of rats, Bergstrom and Norman^-" 

 proved the origin of both cholic and chenodesoxycholic acids from choles- 

 terol. These acids were present in bile as their taurine conjugates. Byers 

 and Biggs^-^ confirmed the transformation of cholesterol into cholic acid in 

 the rat. 



The excretion of cholesterol and of cholic acid in the bile varies in thyroid 

 conditions in rats. Thus, Thompson and Vars^-^ reported that the ex- 

 cretion of cholic acid is reduced in both hyperthyroidism and hypothyroid- 

 ism, whereas the proportion of cholesterol excreted in the bile is a reflection 

 of thyroid activity. 



Robbins and co-workers^-^ demonstrated the remarkable ability of 

 isolated rat liver to synthesize and degrade cholesterol over a prolonged 

 period. When isolated livers were perfused with a solution containing 

 whole rat blood diluted 1 : 3 with a solution of electrolytes, crystalline al- 

 bumin, amino acids, and vitamins, bile was continuously formed for as 

 long as eleven hours. The initial perfusate levels of 13.8 mg. % of choles- 

 terol and 1.2 mg. % of cholate were changed to 18.0 and 1.4 mg. %, re- 

 spectively, by the end of the perfusion. The bile formed had an average 

 composition of 6.3 mg. % of cholesterol, and 117 mg. % of cholate. The 

 rate of disappearance of injected cholesterol, however, could not be in- 

 creased by the administration of bile salts, although there was an increase 

 in cholesterol excretion in the bile.^^^ 



Byers and Biggs^-^ demonstrated that the cholesterol -> cholic acid re- 

 action is not a reversible one. When tritium-labeled cholic acid, prepared 

 by biosynthesis in the rat, was fed to rats with bile-duct obstruction, there 

 was no evidence of tagged cholesterol in the body store. Biggs and Krit- 

 chevsky^^^ had previously demonstrated that tritium-labeled cholesterol is a 

 suitable tracer compound for biologic investigations of cholesterol metab- 

 olism. 



32" S. Bergstrom and A. Norman, Proc. Soc. Exptl. Biol. Med., 83, 71-74 (1953). 



321 S. O. Byers and M. W. Biggs, Arch. Biochem. Biophys., 89, 301-304 (1952). 



322 J. C. Thompson and H. M. Vars, Proc. Soc. Exptl. Biol. Med., 83, 246-248 (1953). 



323 E. D. Robbins, S. Burton, J. Goerke, and M, Friedman, Proc. Soc. Exptl. Biol. Med., 

 83, 212-214(1953). 



324 M. Feldman, Jr., and T. Weinberg, Proc. Soc. Exptl. Biol. Med., 73, 619-620 

 (1950). 



325 M. Biggs and D. Kritchevsky, Arch. Biochem. Biophys., 36, 430-433 (1952). 



