INTERMEDIARY METABOLISM OF CHOLESTEROL 401 



the capacity to form cholesterol esters. No ester cholesterol was synthe- 

 sized in the tissues of the dog following hepatectomy. 



(8) The Nature of the Cholesterol -Synthesizing Enzyme 



It is now recognized that the biosynthesis of cholesterol requires both an 

 enzyme and a co-factor. It is probable that CoA is the coenzyme portion 

 of the enzyme system. Rabinowitz and Gurin^^-' reported the successful 

 fractionation of a rat liver homogenate into a water-soluble enzyme system 

 which is capable of incorporating C^^-acetate into cholesterol. Bucher-*^ 

 also demonstrated that the carboxyl carbon of acetate was incorporated 

 into cholesterol when catalyzed by rat hver homogenates. It was later 

 sho\^^l that the acti\dty of the homogenate was confined to the "microsome- 

 plus-soluble" fraction, while the mitochondria were apparently not es- 

 sential for the synthesis. 2^* 



6. The Intermediary Metabolism of Cholesterol 



(1) Introduction 



The various anabolic and catabolic reactions which are related to choles- 

 terol are exceedingly numerous and complex. According to the widespread 

 experimental e\'idence available, there is no question that cholesterol can 

 be destroyed by most tissues, as well as synthesized. Of greater impor- 

 tance, insofar as cholesterol is concerned, is the formation of related com- 

 pounds from cholesterol which have specific physiologic effects. These in- 

 clude the steroid hormones. Cholesterol is the mother substance of the 

 bile acids, and may be converted to vitamin D via 7-dehydrocholesterol. 

 Finally, cholesterol may be excreted as such via the bile and the intestinal 

 mucosa. There is e^adence that some cholesterol may be excreted in the 

 urine under certain conditions. Cornforth et al^^^ described a new (1953) 

 chemical method for effecting the degradation of the ring structure of 

 cholesterol w^hich involves the opening of ring B and the splitting off of 

 ring A as 2-methyl-cyclohexanone, by pyrolysis. The early stages can be 

 carried out on cholesterol ozonide or, more effectively, on cholest-5-ene. 



"2 J. L. Rabinowitz and S. Gurin, Biochim. et Biophys. Acta, 10, 345-346 (1953). 

 "3 N. L. R. Bucher, /. Am. Chem. Soc, 75, 498 (1953). 



"^ N. L. R. Bucher, J. W. Grover, and R. Kingston, Federation Proc, 13, 19-20 

 (1954). 



"5 J. W. Cornforth, G. D. Hunter, and G. Popjdk, Biochem. J., 54, 590-597 (1953). 



