386 



VIII. 



CHOLESTEROL AND RELATED STEROLS 



are the source of the carbons of cholesterol; under these conditions, the 

 squalene (or steroid) derived from these isoprenoid precursors would be 

 labeled as indicated in Fig. 1. 



The scheme for the utilization of the three branched-chain acids in the 

 synthesis of squalene and cholesterol, as suggested by Bloch, Clark, and 

 Harary,^''^ is given in the following series of equations. 



Higher fatty acids 



'CH3COSC0A 

 VCH3COCH2COSC 



:;oA/ 



HCCOOH 

 CH3C 



CH2COOH 

 CH3C— OH 



CH2COOH 

 Czs-/3-Methyl 

 glutaconic acid 



±C02 



'\CH-=CHC00H - 

 Dimethyl acrylic acid 



CH2COOH 



/3-Methj4 glutaric acid 



±C02 



OH 



CHsy I 



>CCH2C00H 

 CH3/ 



/3-Hydroxy-/3-methyl 

 butyric acid 



Squalene 



PH 



'NCHCH2COOH 

 CH3/ 



Isovaleric acid 



Cholesterol 



Proposed Scheme for the Conversion of Branched-Chain Acids to Squalene and Choles- 



teroP°4 



The proof of the scheme of conversion of the branched-chain acids to 

 squalene and cholesterol rests upon the observed isotope distribution pat- 

 tern. The fact that acetate may act as a source of the five-carbon (iso- 

 prenoid) units which can be converted to cholesterol has been supported 

 by the data of Bonner and ArreguiUj^^" which showed that acetate could 



"» J. Bonner and B. Arreguin, Arch. Biochem., 21, 109-124 (1949). 



