164 III. OXIDATION AND METABOLISM 



glucose must be available for the oxidation of 1.5 g. of fatty acid; this is a 

 1 : 1 ratio on a molecular basis. The appearance of a diabetic acidosis when 

 the F. A. : G ratio was less than 2 : 1 was explained by Shaffer^''^ as due to the 

 uneven distribution of metabolites. Details of these concepts have 

 been presented elsewhere (see page 122). 



Since the demonstration that more than one molecule of ketone bodies 

 originates from each fatty acid oxidized, and especially since the demon- 

 stration of the possibility of synthesis of acetoacetate from acetic acid 

 molecules, the theory that a quantitative relationship exists between the 

 ketone bodies and the glucose oxidized has become less popular. However, 

 the current concept that the ketone bodies must be oxidized via the tri- 

 carboxylic acid cycle with oxaloacetic acid, H00C-C0-CH2-C00H, as 

 the catalytic agent, is, in reality, an exposition of the original theory of 

 Shaffer. In fact, Medes and her associates" state that "there now exists 

 a body of circumstantial evidence indicating that the metabolism of fatty 

 acids, whether at the acetate or acetoacetate level, is coupled with a 

 carbohydrate intermediate, M^hich may be oxalacetate." 



(a) Theories to Explain the Mechanism of the Action of Carbohydrate on 

 Ketosis. The action of carbohydrates in preventing or abolishing ketosis 

 has been explained on the basis of ketolysis and on that of antiketogenesis. 

 According to the ketolysis theory, the oxidation of carbohydrate or of 

 substances which are potential sources of carbohydrate causes the dis- 

 appearance of ketosis and ketonuria by producing a concomitant destruc- 

 tion of ketone bodies. One explanation of this effect is that acetoacetate 

 and the active carbohydrate intermediate are conjugated, and that the 

 new compound is capable of being oxidized. Another suggestion is that 

 the oxidation of acetoacetate results from a catalytic effect exerted by 

 carbohydrate, although all evidence indicates that the oxidation of the 

 ketone bodies is bound up with the metabolism of finite amounts of carbo- 

 hydrate. The first of these theories has been supported by the experi- 

 mental results of Deuel and associates. ^^^ 



According to the antiketogenesis theory, carbohydrate is preferentially 

 oxidized by the animal body; consequently, when carbohydrate is available 

 for oxidation, the formation of ketone bodies is sufficiently suppressed so 

 that the quantity produced by the liver does not exceed the capacity of 

 the tissues to oxidize them. If this concept were correct, there would be 

 no direct relationship between the oxidation of glucose and that of aceto- 

 acetate. Cohen^**^ suggested that carbohydrates reduce ketonuria because 

 of antiketogenesis; this results from the fact that the carbohydrate inter- 

 mediates which compete with those of fat for the oxidative enzyme surfaces 



