INTERMEDIARY METABOLISM OF CHOLESTEROL 413 



covered as COo in three hours. Thus, the hver appears to be not only the 

 chief organ of synthesis of cholesterol, but also the tissue in which degrada- 

 tion of the side-chain of the sterol takes place. On the other hand, baby 

 brain, previously found to be one of the most active sites of cholesterol 

 synthesis, is unable to oxidize the side-chain carbon (C26) to CO2. Thus, 

 rapid synthesis and destruction do not necessarily coexist in the same tis- 

 sue. 



Because of the resistance of the ring-labeled cholesterol to oxidation 

 (cholesterol-4-C^^) in the ring, Siperstein and co-workers ^^"^ were able to 

 follow the enterohepatic circulation of the bile salts originating from it. 

 Thus, after the intravenous injection of cholesterol-4-C'^, the biliary C^^- 

 containing products were absorbed from the intestine, to be reexcreted in 

 the bile. Fifty per cent of the bile products containing C^'' which were pres- 

 ent in the duodenum were reexcreted in the bile within four hours from the 

 time that its administration was completed. Ninety per cent of the biliary 

 products which were present in the intestine for the second time were ab- 

 sorbed and reexcreted in the bile a third time. These biliary products en- 

 ter the enterohepatic circulation, reaching the liver via the portal circula- 

 tion; in sharp contrast to this, cholesterol is absorbed from the intestine 

 by way of the lymph. 



On the other hand. West and Todd^^ stated that "cholesterol is ehminated 

 from the body chiefly in the intestinal secretions . . . and not in the bile, as 

 previously supposed." In support of this statement, the results of a 

 number of workers are cited.®"'^^^-^^^ Thus, while cholesterol itself is ex- 

 creted into the gut via the wall of the intestine, certain end-products of 

 cholesterol metabolism, namelj^, the bile acids, are excreted in the bile. 

 This concept has been repeatedly confirmed in the aforementioned works. 



Another possible explanation of the fate of metabolized cholesterol w^as 

 proposed by Cook,^'^ who suggested that the sterol was converted to fatty 

 acids, inasmuch as a correlation apparently existed between the amount of 

 cholesterol metabolized and the increase of fatty acids in the feces. *^* 

 In a later study. Cook et al.^^'^ reported a loss of unsaponifiable matter 

 (cholesterol) of the same order as the increase in the light petroleum-insolu- 

 ble fecal lipids which occurred concomitantly. It is reported that an opti- 



350 M. D. Siperstein, H. H. Hernandez, and I. L. Chaikoff, .4m. ./. Physiol., 171, 297- 

 301 (1952). 



3" H. Beumer and F. Hepner, Z. ges. exptl. Med., 64, 787-797 (1929). 



3"W. M. Sperry, /. Biol. Chem., 68, 357-383 (1926); 71, 351-378 (1926-1927); 

 81, 299-319 (1929); 85, 455-463 (1929-1930). 



«3 R. P. Cook, Biochem. J., 32, 1191-1199 (1938). 



354 R. P. Cook, N. Polgdr, and R. O. Thomson, Biochem. J., J,7, 600-605 (1950). 



