80 III. OXIDATION AND METABOLISM 



acetate stimulated the oxidation, and it is suggested that the oxidation of 

 acetate proceeded through the citrate cycle. 



b. Multiple Alternate Oxidation Theory. According to this hypothesis, 

 fatty acids are simultaneously oxidized at alternate carbon atoms, in 

 contradistinction to the stepwise procedure suggested in the original /3- 

 oxidation theory. Under these circumstances, capric acid would be 

 immediately oxidized to a polyketonic acid containing ten carbon atoms 

 before any rupture of the fatty acid chain could take place. Subsequent 

 splitting of the polyketone might then be in such locations as to yield one 

 or more molecules of acetoacetate. The oxidation and breakdown of 

 capric acid might be pictured as follows : 



CH3 • CHo • CHo • CH2 • CH2 • CH2 • CHo • CH, • CH, • COOH 

 Capric acid 



CH; 



O 



CH 



O 



J. 



CH 



O 



O : 



uM 



CHo ClCHo- COOH 



A B 



Polyketone of capric acid 

 Possible Oxidation of Capric Acid by Multiple Alternate Oxidation 



Thus, capric acid might yield two ketone body molecules plus one acetate 

 if the rupture obtained at .4 and B simultaneously. Likewise, it might 

 also yield five acetate molecules if a splitting occurred at all possible weak 

 points in the molecule. 



Hurtley^^ first proposed the scheme of multiple oxidation. Jowett 

 and QuasteP-'^^'^^ later suggested the multiple alternate oxidation theory 

 to explain the fact that caprylic and capric acids yielded more than one 

 ketone body per molecule, as contrasted with the result when butyric or 

 caproic acid was employed as the substrate. Leloir and Munoz^^ likewise 

 confirmed the greater ketone body production of long-chain acids by liver 

 slices. 



Butts and associates-^ noted that the administration of caprylic acid 

 gave rise to twice the amount of ketone bodies in the urine of the fasting 

 rats as did an isomolecular amomit of butyric or caproic acids. It was 

 suggested that this might be attributed to a 5-oxidation. However, in a 

 later report,-^ after it was found that other long-chain acids were responsible 

 for increasing ketone body production in fasting rats in proportion to the 

 length of the fatty acid chain, it was suggested that, although butyric and 



38 W. H. Hurtley, Quart. J. Med., 9, 301-408 (1915-1916). 



39 M. Jowett and J. H. Quastel, Biochem. J., 29, 2143-2158 (1935). 



