PRODUCTS RELATED TO CHOLESTEROL 415 



phenanthrene ring is not ruptured, and the end-product of metabolism is 

 excreted when the side-chain has been partially or completely oxidized. 

 There seems to be adequate proof that cholesterol can be converted to 7- 

 dehydrocholesterol, and that the resulting product is then transformed to 

 vitamin D3 in the skin following irradiation, with the result that ring B is 

 ruptured. However, the proportion of cholesterol which follows this route 

 of degradation must be infinitesimal from a quantitative standpoint, in 

 comparison with that which follows other metabolic pathways. 



In the main, the side chain of cholesterol is only partially removed to 

 form bile acids, which are excreted via the bile. Although the bile acids 

 are reabsorbed to some extent, and undergo a cyclic absorption and re- 

 excretion, they are eventually lost via the m'ine as urobihn and urobilinogen. 

 Cholesterol itself is excreted mainly by way of the intestinal mucosa and the 

 large intestine. The proportion of cholesterol which is metabolized to the 

 bile acids constitutes about 90% of that broken down, while only 10% are 

 excreted as such. Although it has been reported that cholesterol is ex- 

 creted in the urine, the amount is small, and it does not amount to any ap- 

 preciable proportion of the total, under normal conditions. Likewise, the 

 proportion of cholesterol from which the side-chain is removed, with the 

 consequent formation of the steroid hormones, must constitute only a very 

 small fraction of the total metabolized. 



7. The Intermediary IMetabolisni of Products Related to 



Cholesterol 



(1) Ergosterol 



Although ergosterol is not a normal component of the tissues of the ani- 

 mal, evidence is increasing that its synthesis in the fungi resembles that of 

 cholesterol in the animal. Thus, Ottke, Simmonds, and Tatum,^^" using 

 Neurospora crassa mycehum (red bread mold) and a mutant which re- 

 quires acetate, concluded that the acetate metabohsm here resembles that 

 of the rat in that acetate is the principal precursor of fat and sterol. In a 

 later study, Ottke and associates^^^ demonstrated that 90% of the carbon 

 in ergosterol, in Neurospora crassa, as well as in the carbon of the fatty 

 acids, was derived from acetate. It was calculated that the ergosterol was 

 made up of fifteen methyl and thirteen carboxyl carbons (or fourteen of 

 each) when acetate was the sole source of carbon for the sterol synthesis. 



'«> R. C. Ottke, S. Simmonds, and E. L. Tatum, /. Biol. Chem., 186, 581-589 (1950). 

 3" R. C. Ottke, E. L. Tatum, I. Zabin, and K. Bloch, /. Biol. Chem., 189, 429-433 

 (1951). 



