THE BIOSYNTHESIS OF RADIOACTIVE 

 CHOLESTEROL BY SURVIVING LIVER SLICES 



SAMUEL GURIN and ROSCOE 0. BRADY 



It is now established that surviving shces of rat Uver are 

 able to utilize carbon atoms of acetate (Block, Borek and 

 Rittenberg, 1946), acetone (Borek and Rittenberg, 1949), 

 pyruvate (Bloch, 1948; Brady and Gurin, 1950a), butyrate, 

 hexanoate and octanoate (Brady and Gurin, 1950a), as well 

 as the isopropyl fragments of isovalerate (Brady and Gurin, 

 1951) for the biosynthesis of cholesterol. Although the 

 results obtained with ^^C or ^^C may be regarded as a reflection 

 of incorporation into, rather than net synthesis of cholesterol, 

 nevertheless, the information so derived is of considerable 

 value in attempting to understand the mechanism of this 

 biosynthesis. 



Until recently, it has been believed that only those pre- 

 cursors which are capable of being degraded to acetate or 

 two-carbon fragments are utilized by mammalian tissue for 

 the biosynthesis of cholesterol. Since the initial demon- 

 stration by Bloch, Borek and Rittenberg (1946) that liver 

 slices can transform labelled acetate into cholesterol, abundant 

 confirmatory evidence has been reported from several 

 laboratories. Little and Bloch (1950) have studied the 

 incorporation of [1-^*C] acetate, [2-^*0] acetate, as well as 

 acetate labelled with ^^C and ^^C into cholesterol. The methyl 

 carbon was shown to be incorporated into positions 18, 19, 

 26, 27 and probably 17, while carbon atoms 25 and probably 

 10 were derived from the carboxyl of acetate. The ratio 

 of CH3 to COOK carbons incorporated into cholesterol was 

 found to be 1 • 27. It is apparent that some decarboxylation 

 occurs during the process. More carboxyl groups of acetate 

 are incorporated into the nucleus than into the iso-octyl side 



ISOTOPES 17 3 



