390 VIII. CHOLESTEROL AND RELATED STEROLS 



from the methyl group. The identification of the source of the carbon 

 atoms in cholesterol is indicated in the equation below: 



The Conversion of Doubly Labeled Acetic Acid into CholesteroP'^ 

 (6) Factors Altering the Biosynthesis of Cholesterol 



a. Age. The synthesis of cholesterol apparently proceeds most rapidly 

 in the young animal; a large amount of the sterol is necessary for the 

 rapidly-developing tissues. Rosenman and Shibota,^^- using the concen- 

 tration of biliary cholesterol as an index of hepatic synthesis, were able to 

 demonstrate a considerably greater rate of synthesis in the young rat as 

 compared with that in the adult animal. 



b. Nutritional State. According to Tomkins and Chaikoff,^^^ the 

 nutritional state has a profound effect upon the extent of cholesterol syn- 

 thesis. Thus, when rats were fasted for twenty-four hours or longer, 

 there was a marked decrease in the capacity of the liver to synthesize 

 cholesterol from acetate. Likewise, caloric restriction for several days 

 reduced cholesterol synthesis. It was found that the ability to synthesize 

 cholesterol could be restored when glucose, a protein hydrolysate, or fat, 

 was fed to the rat. 



c. Cholesterol Intake. The administration of exogenous cholesterol 

 has been shown to reduce markedly the proportion of cholesterol which is 

 synthesized. Thus, Gould and Taylor-^^ observed that the rate of synthe- 

 sis of cholesterol in the livers of dogs and rabbits previously on a high- 

 cholesterol diet was only a few per cent of that which occurred in animals 

 on a cholesterol-free diet. Moreo\^er, the rate of conversion of labeled 

 acetate into cholesterol was also found to be markedly reduced in the ani- 

 mals previously maintained on the high -cholesterol regimen. This would 

 indicate that the rate of cholesterol synthesis is related to the amount of 



^'^ A. White, P. Handler, E. L. Smith, and De W. Stetten, Jr., Principles of Biochemis- 

 try, McGraw-Hill, New York, 1954, p. 494. 



"2 R. H. Rosenman and E. Shibota, Proc. Sac. Exptl. Biol. Med., 81, 296-298 (1952). 

 "3 G. M. Tomkins and I. L. Chaikoff, J. Biol. Chem., 196, 569-573 (1952). 

 "4 R. G. Gould and C. B. Taylor, Federation Proc, 9, 179 (1950). 



