Acetone Metabolism 231 



acetylation of phenyl- y-aminobutyric acid with acetone. 

 Here we see the use of another indicator of metabohsm. In 

 this case, the acetylation of a foreign amine is used as evidence 

 of the occurrence of "acetate" in the intermediary metabolism 

 of a compound (Bloch and Rittenberg, 1944). 



The above results could be explained by a pathway of 

 utilization of acetone via carboxylation to acetoacetate, with 

 subsequent oxidation of the acetoacetate. 



C*H3COC*H3 + C02 -> C^HgCOC^Ha-COOH 



Evidence that the carboxylation reaction occurs has been 

 obtained by Plant and Lardy (1950) and Coon (1950). It 

 would be expected that the acetoacetic acid from the above 

 reaction would be metabolized by conversion to methyl 

 labelled acetate and then be oxidized via the tricarboxylic 

 acid cycle: — 



C*H3 • CO • C*H3+C02 -> C*H3 • CO • C*H2 • COOH -> "C^HsCOOH" 



via Krebs cycle 



-> C*-C*-CO-CO-C*-C* (glucose) 



and glycolysis 



Accordingly, the distribution of the tracer in the glucose 

 would be expected to be like that obtained with methyl 

 labelled acetate (Lifson et al., 1948). However when acetone 

 was tested (Sakami, 1950) the results (shown below) were 

 found to be quite different from that found with methyl 

 labelled acetate.*)* 



♦Indicates highest activity, o indicates lower activity. 



I In these and subsequent experiments a comparison will be made between 

 the activities of glycogen obtained under conditions which are not always 

 identical. Although the absolute values are not comparable between the 

 experiments the relative distribution pattern probably is comparable. The 

 method of conducting the glycogen experiments was to fast the animal for 

 24 to 48 hours and then administer the isotopic compound along with un- 

 labelled glucose or glycine. After 3 to 10 hours the animals were sacrificed 

 and the liver was worked up. When glycine was being used a longer time was 

 allowed because of the delayed glycogen deposition with this substrate 

 (MacKay, Wick and Carne, 1940). Usually 2-5 mM. of glycine or 2-5 mM. 

 of glucose were given by stomach tube per 100 g. of rat and 0-5 to 2 mM. of 

 the labelled compound containing 1-5 to 0-5x10* counts/min. Sometimes 

 the labelled compounds were given intraperitoneally, sometimes subcutan- 

 eously. The glucose from the glycogen was usually degraded by bacterial 

 fermentation with Lactobacillus casei (Wood et al., 1945). 



