BIOSYNTHESIS OF CHOLESTEROL. 387 



be used in the synthesis of natural rubber from guayule seedlings (Parthen- 

 ium argentatum) . The indication that the reactions are reversible at the 

 5- and ff-carbon levels is based upon the pro^'en ability of these branched- 

 chain acids to act as sources of carbon for the higher fatty acids, as well as 

 upon the CO2 fixation known to accompany the formation of acetoacetate 

 from isovalerate'^^ and from /3,/3-dimethylacrylate.-''^ 



e. Miscellaneous Compounds. In an extended study of cholesterol 

 SJ^lthesis in vitro in the liver, Brad\^ and his associates-^- noted that C^'*- 

 \dnylacetic acid (CHo.-CH-CHo-COOH), crotonaldehyde (CH3CH:- 

 CH-CHO), acetoin (CHs-CO-CO-CHs), and orsellinic acid (CHs-Cg-- 

 H2-(OH)2-COOH), are unimportant as precursors; the same was found to 

 be true for formate (HCOOH) and for formaldehyde (HCHO). Only 

 aldol (CHs-CHOH-CHz-CHO), which is probably partly converted to 

 acetoacetate, appeared to have any importance as a source of cholesterol. 



(4) Intermediates in Cholesterol Synthesis 



a. Squalene. The most significant evidence of the course of cholesterol 

 synthesis in the animal bod}' was the discovery b}^ Langdon and Bloch-'^ 

 that squalene is convertible to cholesterol in the mouse. Squalene is a 

 highly unsaturated hj^drocarbon with an empirical formula of C30H50, which 

 was first isolated from shark liver oil of the genus Zameus by Tsujimoto^^* 

 in 1906; it was later identified as squalene,-^^ the formula of which is given 

 below: 



CH3 CH3 CH3 CH3 



H3\ 1 I II /CH3 



>C : CH • CH0CH2C : CHCH2CH0C : CHCH2CH2CH : CCH2CH2CH : CCH2CH2CH : C< 

 H3/ ^CH, 



Squalene 



Squalene has been found to be ^Wdely distributed in the liver oils of the 

 Elasmohranchii. Tsujimoto-^® reported the presence of this hydrocarbon 

 in sixteen of thirt3^-six species of elasmobranch fishes in Japanese waters, 



211 M. J. Coon, ./. Biol Chem., 187, 71-82 (1950). 



"2 R. O. Bradv, J. Rabinowitz, J. van Baalen, and S. Gurin, /. Biol. Chem., 193, 137- 

 143(1951). 



*'' R. G. Langdon and K. Bloch, J. Biol. Chem., 200, 135-144 (1953). 



"^ M. Tsujimoto, /. Sac. Chem. Ind. Japan, 9, 953 (1906); cited by M. Tsujimoto, 

 Ind. Eng. Chem., 8, 890 (1916). 



215 M. Tsujimoto, Ind. Eng. Chem., 8, 889-896 (1916). 



"6 M. Tsujimoto, Ind. Eng. Chem., 12, 63-73 (1920). 



