84 III. OXIDATION AND METABOLISM 



in the form of NaHCOs occurred. Jowett and QuasteP- noted that 

 definite quantities of ketone bodies originated when liver sHces were incu- 

 bated in a medium containing acetate. However, the level of ketone body 

 formation was only about one-fifth of that noted with butyrate. 



Experiments in which isotopes were used confirm the fact that acetic 

 acid molecules can condense to form ketone bodies. Thus, Swendseid, 

 Barnes et al.^^ reported that the acetoacetic acid isolated from the urine 

 of rats fed CH^C^^OOH contained C^^ in the carboxyl groups. Moreover, 

 acetone from acetoacetate contained C^^ in the carbonyl group. Wein- 

 house, Medes, and Floyd^^ have shown that a similar fate may involve 

 the acetic acid formed by rupture of the terminal carbon atoms of long- 

 chain acids. When caprylic acid, which was labeled only in the carboxyl 

 group, was fed to rats, the ketone acids had isotopic carbon in the carboxyl 

 groups, while acetone derived from them was labeled in the carbonyl group. 



CH3(CH2)6C*OOH > 3CH3COOH + CH3-C*00H 



2CH3C*OOH > CH3C*OCH2C*OOH > CH3C*OCH3 + 0*0^ 



CHa-COOH + CH3C*00H > CH3CO-CH2C*OOH > 



CH3COCH3 + C*02 



> CH3 • C*0 • CH2 • COOH > 



CH3C*0-CH3 + CO2 

 2CH3-COOH > CH3COCH2COOH > CH3COCH3 + CO2 



Possible Pathways for the Formation of Ketone Bodies in the Metaliolism of 



Caprylic Acid 



A random combination of isotopically-labeled and ordinary acetic acid 

 can therefore take place in a variety of ways, with the result that some 

 acetoacetate, in which the carbonyl group is labeled, will be produced. 



Medes, Weinhouse, and Floyd,^^'^^ employing isotopic butyric acid and 

 caprylic acid, found that some acetoacetate originated from direct {(3-) 

 oxidation, although in this case also a proportion of the ketone bodies 

 resulted from the condensation of the acetic acid" formed from the butyric 

 acid. 



One observation is difficult to harmonize with the /3-oxidation-acetic 

 acid condensation theory. If the acetic acid removed by j8-oxidation is 

 quantitatively changed to ketone bodies, then caproic acid should yield 1.5 



f" M. E. Swendseid, R. H. Barnes, A. Hemingway, and A. O. Nier, /. Biol. Chem., 142, 

 47-52 (1942). 



" S. Weinhouse, G. Medes, and N. F. Floyd, J. Biol. Chem., 153, 689-690 (1944). 

 55 G. Medes, S. Weinhouse, and N. F. Floyd, /. Biol. Chem., 157, 35-41 (1944). 

 « S. Weinhouse, G. Medes, and N. F. Floyd, Am. J. Med. Sci., 207, 812-813 (194-1). 

 " G. Medes, N. F. Floyd, and S. Weinhouse, /. Biol. Chem., 162, 1-9 (1946). 



