TRIGLYCERIDES AND FATTY ACIDS 83 



CO-CHi-CO-COOH), exhibits a marked metabolic activity in vitro,^''-'^^ 

 the Q:,7-diketo homologue of octanoic acid was found by Lehnmger^^ 

 to be poorly absorbed from the intestine of the rat. As much as 67% 

 could be recovered from the gastrointestinal tract twelve hours after the 

 diketo acid was fed to rats; this poor absorption was attributed to the low 

 diffusibility. It was later shown, however, that broken cell preparations 

 of rat liver were able to oxidize this compound at a slow rate.*^ 



Moreover, although the /?-oxidation theory in its original form fails to 

 explain the greater ketone body formation from long-chain acids than 

 from short-chain ones, the ^3- oxidation-acetic acid condensation theory of 

 MacKay et al}° pro\'ides as satisfactory an explanation of this phenomenon 

 as does the multiple alternate oxidation theory. The criticism of Stadie,*^ 

 that the presence of acetic acid in the liver has not been proved, is im- 

 portant; however, it may not be valid, if the formation is instantaneous, 

 and if any acetate formed is immediately oxidized or converted to ketone 

 bodies. The data accumulated by means of isotopic acids, and of CH3- 

 CO-CoA, which have been discussed in relation to the synthesis of fatty 

 acids, and which will be elaborated in the following section, would seem to 

 be sufficiently substantiated to dispel any doubt that two-carbon inter- 

 mediates are formed in the tissues. Crandall and Gurin^' interpreted the 

 fact that /3-labeled octanoate gives rise to acetoacetate with a predominance 

 of the isotopic carbon in the carboxyl group as evidence that multiple 

 alternate oxidation does not constitute a significant pathway in the oxida- 

 tion of octanoate. 



c. jS-Oxidation-Acetic Acid Condensation Theory. According to this 

 theory, the breakdown of fatty acids proceeds by /3-oxidation, but the ace- 

 tic acid molecules set free are able to condense, to yield acetoacetate mole- 

 cules. Support for this theory comes from several types of experiment. 

 Thus, as early as 1913, Friedmann*- reported that the perfusion of liver 

 with acetic acid resulted in the formation of ketone bodies. MacKay and 

 collaborators^*^ noted that the administration of acetic acid to a phlorhizin- 

 ized dog increased the level of ketonuria. Moreover, when this acid was 

 fed to fasting rats, a definite increase in ketone body excretion over and 

 above that produced by control rats receiving a similar quantity of sodium 



« H. A. Krebs and W. A. Johnson, Biochem. J., 31, 772-779 (1932). 

 « A. L. Lehninger, J. Biol. Chem., 148, 393-404 (1943). 

 " A. L. Lehninger, J. Biol. Chem., 153, 561-570 (1944). 



" E. M. MacKay, R. H. Barnes, H. O. Came, and A. N. Wick, J. Biol. Chem., 135, 

 157-163 (1940). 



" D. I. Crandall and S. Gurin, J. Biol. Chem., 181, 829-843 (1949). 

 " E. Friedmann, Biochem. Z., 55, 436-442 (1913). 



