The metabolism of acetone. I. Gross aspects of catabolism and excretion.

Early evidence for the metabolic activity of acetone was derived from studies showing a partial disappearance of administered doses of the compound (1, 2). It is clear from these investigations, and from subsequent work (3,4), that most of the acetone excreted as volatile iodoform-forming substance appears in the exhaled air; a smaller fraction is excreted in the urine. Schwarz (1) demonstrated that the fraction of administered acetone recoverable in the breath becomes smaller as the size of the administered dose is decreased. About 55 per cent of the acetone was exhaled and about 1.2 per cent was excreted in the urine when doses of 366 to 606 mg. per kilo were administered to healthy dogs; only 18 per cent was exhaled when the dose was 3.5 mg. per kilo. These findings are compatible with the view that any acetone, if formed in small amounts in normal metabolism (1, 4-7), is largely metabolized. Apparent conversions of acetone to acetoacetic acid (7), /?-hydroxybutyric acid and lactic acid (8), and glucose (9) have been reported. However, Koehler et al. (7) found no increase in the blood concentrations of /%hydroxybutyric acid or glucose when human subjects were given 10 gm. of acetone intravenously. Recently Borek and Rittenberg (10) have demonstrated the incorporation of deuterium from deuterioacetone into the cholesterol of rat liver slices. This observation provided conclusive evidence of metabolic activity of acetone in this tissue. Deuterioacetone is unsatisfactory for quantitative studies of acetone metabolism because an unknown fraction of the deuterium may be lost by enolization of the acetone and its potential metabolic products. CY4H3COC4Ha was used in the present studies.