Acetoacetic acid formation in vitro from odd and even numbered radioactive fatty acids.

Incubation of carboxyl-labeled fatty acids (RCi400H) with liver slices gave rise to Cl402 and labeled acetoacetic acid (1, 2). In the case of even numbered acids, much more of the radiocarbon appeared in the keto acid than was oxidized to C1402; however, the reverse situation occurred when acids of an odd number of carbons were used (2). Previously, studies made with non-labeled acids had yielded similar differences between Qo, and total acetoacetic acid production (3). The acetoacetic acid formed from carboxyl-labeled octanoic acid (1,4, 5) and hexanoic acid (4) has been shown to be asymmetrically labeled with respect to the carboxyl and carbonyl groups. That the acetoacetic acid formed by washed liver homogenates was the result of recondensation of 2-carbon fragments has been demonstrated (5, 6). In the latter reports, a mechanism was suggested to explain the asymmetry of the acetoacetic acid. In the present paper further studies on the metabolism of radioactive fatty acids by liver and kidney slices are presented in which the radiocarbon respired in the CO2 and present in the carbonyl and carboxyl groups of acetoacetic acid was determined The substrates used were carboxyllabeled pentanoic, hexanoic, heptanoic, octanoic, nonanoic, and dodecanoic acids, and (Yand p-labeled octanoic acids.