388 Vlir. CHOLESTEROL AND RELATED STEROLS 



including the basking shark {Celorhinus maximus).-" Hilditch^'^ also 

 demonstrated the presence of squalene in the hver oils of the Squalidae and 

 of other shark families. Strangely enough, squalene was discovered by 

 Thorbjarnarson and Drummond^^^ to be a component of olive oils ob- 

 tained from a number of geographical sources. For a further, more com- 

 plete, discussion of the distribution of squalene, the reader is referred to 

 The Lipids, Vol. I, pages 400-402. 



Langdon and Bloch'-^^^ found that squalene was readily absorbed from 

 the intestine of the rat, and that 5 to 10% could be recovered from the 

 tissues. When labeled acetate was fed together with natural squalene, 

 the recovered squalene was radioactive.^^" The rate of turnover was found 

 to be exceedingly rapid ; a maximal incorporation of acetate into squalene 

 occurred within thirty minutes. Since only traces of squalene are nor- 

 mally present, it is suggested that this compound is an intermediate in a 

 rapid metabolic process. Squalene was found to be a precursor of choles- 

 terol, but not of fatty acids, in mice.^^^ Although the experimental data 

 of Langdon and Bloch-^^--^'' with natural squalene would seem to be deci- 

 sive, Tomkins et al.-^^ failed to demonstrate the synthesis of cholesterol 

 from deuterium-labeled synthetic squalene or from a synthetic C'*-labeled 

 squalene. Wiiersch, Huang, and Bloch^"* are of the opinion, on the basis 

 of their extensive degradation of the cholesterol side-chain, that choles- 

 terol is built up from isoprene units. According to Woodward and Bloch,^"^ 

 squalene, synthesized from isoprenoid groups, can be cyclized into choles- 

 terol by a mechanism suggested earlier by Robinson, ^^^ or by an alternative 

 trans- formation. ^^^ Studies of the nature of labeled biosynthesized choles- 

 terol, investigated by degradation reactions, by Cornforth et al.^^^'^^* and 

 by Dauben and co-workers,--^ tend to support this concept of the cycliza- 

 tion of squalene into cholesterol. The distribution of the labeled acetate 

 carbon in the quaternary methyl carbons of biosynthesized cholesterol is 

 also believed to corroborate this theory of its synthesis. ^^^-^-^ 



2" M. Tsujimoto, Bull. Chem. Soc. Japan, 10, 144-148, 149-153 (1935); /. Chem. 

 Soc. Japan, 55, 702-741 (1934); Chem. Ab.st., 28, 6484 (1934). 



218 T. P. Hilditch, The Chemical Constitution of the Natural Fats, Wilev, New York, 

 1947. 



2>9 T. Thorbjarnarson and J. C. Drummond, Analyst, 60, 23-29 (1935). 



"0 R. G. Langdon and K. Bloch, ./. Biol. Chem., 200, 129-134 (1953). 



221 G. M. Tomkins, I. L. Chaikoff, W. G. Dauben, H. L. Bradlow, and P. A. Srere, 

 J. Am. Chem. Soc, 74, 6145-6146 (1952). 



"2 R. B. Woodward and K. Bloch, /. Am. Chem. Soc, 75, 2023-2024 (1953). 



223 R. Robinson, Chemistrij & Industry, 53, 1062-1063 (1934). 



22" J. W. Cornforth, G. D. Hunter, and G. Popjdk, Biochem. J., 53, xxiv-xxv (1953). 



225 W. G. Dauben, S. Abraham, S. Hotta, I. L. Chaikoff, H. L. Bradlow, and A. H. 

 Soloway, /. Am. Chem. Soc, 75, 3038 (1953). 



