The metabolism of acetone in the intact rat.

Two pathways of acetone utilization in the rat have been indicated. One mechatim involves its carboxylation to acetoacetate (1) ; the second, the production of “formate”’ from acetone methyl carbon (2). This formate has been postulated to arise by a 2and l-carbon cleavage in which “acetate”’ is also formed. In the present investigation, the possibility of a direct oxidation of acetone to a 3-carbon intermediate of glycolysis, such as pyruvate, has been considered. In previous studies (2), methyl-labeled acetone was found to introduce 04 into the glycogen with higher activity in the 3,4than in the 2,5-carbons. This aspect of the isotope distribution was originally considered to have been produced by CO2 fixation, although the 3 ,Ccarbon labeling was somewhat higher than had been anticipated for this mechanism. An alternative explanation was the additional occurrence of a major conversion of acetone to “pyruvate”,2 a pathway which would raise the activity of the 3,4-carbons (and of the 1,6) relative to that of the 2,5.