Acetone Metabolism 235 



distribution with the acetone and lactate is that the 3, 4 

 positions are labelled higher in the case of the acetone. The 

 high labelling in the 3, 4 positions, is considered to reflect the 

 simultaneous occurrence of the C 2 and C\ split of acetone, 

 which yields carboxyl labelled "acetate" and thus 3, 4 labelled 

 glucose. The results are thus in complete agreement with 

 the idea that acetone may be oxidized in part to yield a 

 3-carbon carbohydrate precursor directly and may in part 

 be cleaved to Cg and C^ compounds. 



Although the results with 2, 4 labelled acetoacetate made 

 it fairly certain that acetone Avas not mxCtabolized via aceto- 

 acetic acid, or acetoacetic acid via acetone, Sakami and 

 Lafaye (1951) repeated the experiment with 1, 3-labelled 

 acetoacetate. The results were as follows: — 



CH3 • 14C0 • CH2 • i^COOH 



It is seen that in contrast to the results with carbonyl labelled 

 acetone there was little labelling of the 1, 2, 5, 6 positions and 

 thus no evidence of significant conversion of acetoacetate to 

 acetone. Moreover, since the 3, 4 positions are highly labelled, 

 there is no indication that dilution of acetoacetate was such 

 as to mask detection of the conversion of acetoacetate to 

 acetone. 



The significance of these two pathways of acetone meta- 

 bolism is not apparent at present. It is well known that liver 

 does not utilize acetoacetate as rapidly as does skeletal or 

 heart muscle. Therefore, liver may not be the best organ for 

 study of acetoacetate metabolism. The conversion of 

 acetoacetate to acetone and of acetone to a carbohydrate 

 precursor offers an attractive mechanism for the net con- 

 version of fatty acid to carbohydrate. There has long been 

 a controversy about such conversion but until now there 

 has been no conclusive evidence and indeed no satisfactory 

 mechanism for such net conversion. In heart muscle there 

 is some indication that there may be glycogen formation from 

 ketone bodies (Lackey, Bunde and Harris, 1947). It would 



