412 VIII. CHOLESTEROL AND RELATED STEROLS 



{11) Oxidation of Cholesterol, 

 and the Excretion of Oxidation Products 



Until the experiments of Chaikoff and collaborators, ^^®'^^^ little evidence 

 was available as to whether or not cholesterol can be completely oxidized 

 in the animal body, and how the end-products are excreted. These workers 

 investigated the fate of cholesterol labeled at carbons 4 (in the ring) and 

 26 (in the side-chain). As much as 31% of the side-chain C (C 26) was 

 eliminated in the expired air within twenty-four hours after administra- 

 tion, while none of the ring carbon (C^) appeared as CO2. Intestinal bac- 

 teria were shown to play only a minor role (and possibly none whatsoever) 

 in this oxidation. The ring carbon was found to be eliminated from the 

 body almost entirely with the feces ;^^^ none was excreted in the urine or 

 expired from the lungs as COo. Of that which was excreted in the feces, at 

 least 90% reached the intestinal tract via the bile, as bile acids, while a 

 maximum of 10% was excreted through the walls of the intestine as choles- 

 terol. Friedman et al.^*^ likewise reported that the removal of cholesterol 

 from the rat after intravenous injection involves the conversion and ex- 

 cretion of at least 60% as bile acids. This removal of excess cholesterol 

 requires twelve to twenty-four hours, during which a hypercholesterolemia 

 obtains. Siperstein and Chaikoff ^^^ noted that the majority of the labeled 

 nucleus carbon was excreted in the bile and feces as a saponifiable com- 

 pound; the cholesterol or cholesterol-like compound which reached the 

 intestine through the walls of the intestine was in the form of a non- 

 saponifiable component (presumably unchanged cholesterol, coprostanol 

 (coprosterol), and cholestanol (dihydrocholesterol)). Actually, the non- 

 biliary contribution of fecal cholesterol accounts for only 10% of the total 

 C4-labeled cholesterol excreted by the intestine. ^^^ 



The oxidation of cholesterol by slices of different organs was studied di- 

 rectly by Meier, Siperstein, and Chaikoff, ^^^ making use of a non-toxic, 

 aqueous solution of cholesterol-26-C'''. It was found that sUces of liver, 

 kidney, adrenal, testes, and spleen were able to oxidize the C26 to CO2; 

 the liver was by far the most active. No C"02 appeared after liver slices 

 from animals injected with cholesterol-4-C^^ were incubated. Under iden- 

 tical conditions, as much as 1% of the C^'* of cholesterol-26-C^'* was re- 



'« I. L. Chaikoff, M. D. Siperstein, W. G. Dauben, H. L. Bradlow, J. F. Eastham, 

 G. M. Tomkins, J. R. Meier, R. W. Chen, S. Hotta, and P. A. Srere, /. Biol. Chem., 194, 

 413-416(1952). 



'" M. D. Siperstein and I. L. Chaikoff, /. Biol. Chem., 198, 93-104 (1952). 



3« M. Friedman, S. O. Byers, and B. Gunning, Am.. J. PhrjsioL, 172, 309-316 (1953). 



3« J. R. Meier, M. D. Siperstein, and I. L. Chaikoff, /. Biol. Chem., 198, 105-109 

 (1952). 



