20 Samuel Gurin and Roscoe O. Brady 



cleavage into two-carbon fragments since it has been pre- 

 viously established by Buchanan, Sakami and Gurin (1947) 

 that singly labelled acetoacetate is not significantly rando- 

 mized by liver slices. Furthermore, labelled acetoacetate is 

 neither incorporated into long chain fatty acids by liver 

 slices nor oxidized to any significant extent by this tissue. 

 If labelled acetoacetate is incubated under comparable con- 

 ditions with carrier non-labelled acetate, a small amount of 

 ^*C can be recovered in the isolated acetate. This recovery 

 of ^*C is much too small, however, to account for the incor- 

 poration of acetoacetate into cholesterol. Although acetate 

 may furnish most of the carbons of cholesterol, some of it is 

 incorporated by way of acetoacetate. 



It has been shown by Zabin and Bloch (1950) as well as 

 Price and Rittenberg (1950) that [2-i^C] acetone is converted 

 by the rat to cholesterol and to two-carbon fragments. We 

 have recently confirmed the fact that liver slices not only are 

 capable of converting labelled acetone to cholesterol, but can 

 convert it to acetate. If carrier non-labelled acetate is 

 incubated with [2-^*C] acetone in the presence of liver slices, 

 acetate containing appreciable radioactivity is recovered. If, 

 from the same experiment, one examines the ^*C activity of 

 the isolated long chain fatty acids, it is clear that much of the 

 ^*C of the fatty acids could not have been derived from the 

 acetate. It is reasonable to assume, therefore, that acetone may 

 be degraded to a metabolically active two-carbon fragment 

 which is secondarily converted to acetate. Since acetone 

 is a relatively poor source of acetoacetate via fixation of 

 COg, it is unlikely that very significant amounts of acetone 

 are converted to cholesterol by way of acetoacetate. 



Zabin and Bloch (1950) reported that, in the whole animal, 

 methyl labelled isovalerate is a better precursor of cholesterol 

 than is acetate. Upon incubation with liver slices, methyl- 

 labelled isovalerate was somewhat poorer than acetate in this 

 respect. The reasons for this discrepancy are not clear since 

 isovalerate appears to diffuse readily into the cell. Since the 

 isopropyl moiety of isovalerate or leucine can react rapidly 



