BIOSYNTHESIS OF CHOLESTEROL 397 



that, whereas nicotinamide, pantothenic acid, pyridoxine, meso-inositol, 

 and methionine are concerned with the metabohsm of both cholesterol and 

 fats, vitamin A and choline are concerned only with that of cholesterol. 



j. The Effect of Tissue Injury. Werthessen and Schwenk^^^ demon- 

 strated that the efficiency of biosynthesis of C^^-cholesterol in surviving 

 livers perfused with C^*-acetate varied inversely with the damage to the or- 

 gan. When minimum damage had occurred, a minimum amount of choles- 

 terol was formed. On the other hand, scission of the organ, multiple punc- 

 turing of its surface, the administration of bacterial toxins or of bacteria to 

 the perfusion system, were found to increase the C^^ concentrated in the 

 newly synthesized cholesterol. 



(7) The Site of Cholesterol Synthesis 



The liver has been generally accepted as the chief site of cholesterol 

 synthesis, but recent data have indicated that the capacity to effect this 

 reaction is a generalized one. As indicated earlier, it is possible for liver 

 slices to induce the synthesis of cholesterol from acetate, and broken cell 

 preparations^*^ and homogenates of the liver are also able to effect this syn- 

 thesis. 



Srere and co-workers-^" demonstrated that cholesterol synthesis might 

 be an extrahepatic function, since it proceeded in hepatectomized rats. 

 Later they investigated the possible sites of this reaction. It was evident 

 that the acetate -*• cholesterol reaction could be effected in vitro by surviv- 

 ing slices of beef adrenal cortex. In subsequent studies on hepatectomized 

 rats, Srere and his collaborators^^^ observed that, in addition to the liver 

 and adrenals, the following tissues were able to synthesize cholesterol: 

 kidney, testis, small intestine, and skin. The brain and skin of newborn 

 rats also' synthesized cholesterol, although this capacity was lost in brain 

 shces of adult rats. The skin and liver were considered to be the tissues in 

 which the most active sjmthesis of cholesterol takes place. Human adrenal 

 slices were likewise shown to be active in catalyzing the acetate -* choles- 

 terol reaction. 212 '"2 Gould and Taylor^^* and Srere et al.^''^ likewise dem- 

 onstrated that the cholesterogenic reaction can proceed in skin at a rate 

 comparable to that in liver. Although they also recognized the ability of 

 adrenal cortex to function in a similar manner, they call attention to the 



2«9 N. T. Werthessen and E. Schwenk, Am. J. Physiol., 171, 55-61 (1952). 



z'o P. A. Srere, I. L. Chaikoff, and W. G. Dauben, J. Biol. Chem., 176, 829-833 (1948). 



"1 P. A. Srere, I. L. Chaikoff, S. S. Treitman, and L. S. Burstein, /. Biol. Chem., 183, 

 629-634(1950). 



"2 E. S. West and W. R. Todd, Textbook of Biochemistry, 2nd ed., Macmillan, New 

 York, 1955, p. 928. 



