INTERMEDIARY METABOLISM OF CHOLESTEROL 405 



cholesterol molecule could be effected beyond the ketone stage by Pro- 

 adinomyces, resulting in a disruption of the molecule. Two types of oxida- 

 tion were sho^^^I to occur; these were frequently simultaneous processes. 

 One of these involves ring fission at the carbonyl group, while the second 

 one consists in complete removal of the side-chain, with the result that 

 aetiocarboxylic acid is formed. Thus, cholest-4-ene-3-one yields 3-keto- 

 aetiochol-4-enic acid and isocaproic acid. ^\Tien ring A is disrupted be- 

 tween carbons 3 and 4, the so-called Windaus keto acid is formed. When 

 the fission of the A ring is prevented by blocking the free carboxyl on carbon 

 3 (as in cholesterol acetate), isocaproic acid is still formed by removal of the 

 aliphatic side-chain. In the case of 3,7,12-triketocholanic acid, the side- 

 chain is completely removed, with the formation of 3,7,12-triketoaetio- 

 cholanic acid, but there is no ex^dence of ring fission at any of the suscep- 

 tible points. 



The speed of turnover of cholesterol has been determined in several 

 species of animals. In the rat, the half -life has been given as six days for 

 the liver and thirty-one to thirty -two days for the carcass ;^*^ in the case 

 of the rabbit, the figure was three days for the liver and l.o days for the 

 intestine.'^" London and Rittenberg^^^ estimated the half -life of cholesterol 

 in man as eight days. 



{3) Conversion to Cholic Acid and to Other Bile Acids 



Although it was long suspected that the bile acids are formed from choles- 

 terol, only since the advent of the isotope technic has it been possible to 

 prove the reaction unequivocally. Bloch and co-workers^^^ were the first 

 to prove this interconversion. When deuteriocholesterol was adminis- 

 tered intravenously to a dog after an anastomosis had been established be- 

 tween the gall-bladder and the peh-is of the kidney, it was found that the 

 cholic acid isolated from the urine had the same isotope concentration as 

 that of the injected cholesterol. It was calculated that at least two- 

 thirds of the excreted cholic acid had arisen from the administered choles- 

 terol. 



Zabin and Barker^^^ made a more comprehensive study of the choles- 

 terol -^ cholic acid conversion in a bile-fistula dog, by feeding biosjiitheti- 

 call}' prepared tagged cholesterol. It was sho^^Tl that the cholic acid 

 formed originated from cholesterol by the removal of only three carbons, 

 i.e., numbers 25, 26, and 27. 



"» I. M. London and D. Rittenberg, J. Biol. Chem., 184, 687-691 (1950). 

 "9 1. Zabin and W. F. Barker, J. Biol. Chem., 205, 633-636 (1953). 



