416 VIII. CHOLESTEROL AND RELATED STEROLS 



The methyl carbon of isovaleric acid was shown to participate to a small 

 but significant extent in the synthesis of ergosterol by Neiirospora.^^^ 

 Hanahan and al-WakiP^- proved that 74% to 84% of the carbon of ergos- 

 terol was derived from acetate when the sterol was synthesized by yeast 

 which had previously been CoA-deficient and which was subsequently en- 

 riched. Using this procedure with, labeled acetate, it was found that 

 ergosterol of high specific activity could be prepared. ^^- In a subsequent 

 study of the six-carbon side-chain of ergosterol, by these workers,^®^ it was 

 noted that carbons 23 and 25 were derived from the carboxyl group of acetic 

 acid. 



Although there was some evidence, based upon spectrographic data, that 

 small amounts of erogosterol occur in animals, Schonheimer ei al.^^ dem- 

 onstrated that the amount of ergosterol could not be increased in rats, mice, 

 or rabbits b}^ feeding ergosterol over long periods of time. It was thus 

 shown, in opposition to the results of Page and Menschick,^- that ergos- 

 terol, if absorbed, was not stored. Schoenheimer^^ later proved that, 

 when a mixture of cholesterol and ergosterol was fed to dogs, only choles- 

 terol appeared in the thoracic lymph, and no trace of ergosterol was pres- 

 ent in this fluid. Schoenheimer,^^ however, does not exclude the pos- 

 sibility that biologically important amounts of ergosterol may be ab- 

 sorbed over long periods of time. It was later demonstrated both by 

 Schonheimer and Dam^^ and by Menschick and Page®^ that the laying hen 

 is able to absorb ergosterol if it is given in large amounts. Ergosterol, in 

 common with the phytosterols, has been shown to inhibit cholesterol ab- 

 sorption from the small intestine. ^^ 



{2) Phytosterols 



In 1908, Konig and Schluckebier^^* reported that no phytosterols occur 

 in the body fat, brain, liver, or bile of animals after prolonged feeding with 

 vegetable fats. There is no evidence that the phytosterols are converted 

 to cholesterol; if this were the case, Schoenheimer^^ points out, every rabbit 

 should exhibit a marked atherosclerosis, inasmuch as the level of plant 

 sterols in the feed of rabbits is approximately ten times as high as the dose 

 of cholesterol which provokes atherosclerosis in this species. After the 

 feeding of enormous doses of sitosterol and of other phytosterols to rabbits, 

 as well as to other animals, no demonstrable pathologic changes could be 

 observed. Moreover, no increase in blood cholesterol occurred, nor was 



362 D. J. Hanahan and S. J. al-Wakil, Arch. Biochem. Biophys., 37, 167-171 (1952). 



363 D. J. Hanahan and S. J. al-Wakil, J. Am. Chem. Soc, 75, 273-275 (1953). 



3" J. Konig and J. Schluckebier, Z. Untersuch. Nahr. Genussm., 15, 644-661 (1908). 



