DIABETIC COMA 559 



generally considered that they are derived from the oxybutyria acid, 

 as follows: 



/3-oxybutyric acid is — 



CH^CHOH— CH2— COOH, 



and by oxidation this readily forms — 



CH3— CO— CHa— COOH, 



which is diacetic acid (being two molecules of acetic acid united to 

 each other, as follows) : 



CH3— CO— |0H— Hj— H2C— COOH. 



Diacetic acid is, in turn, readily deprived of its carbon dioxide, forming 

 acetone, 



CH3— CO— CH3. 



All these reactions are easily accomplished in the laboratory, and there 

 seemed to be reason for believing that they may normally occur in the 

 same way in the animal body. Wakeman and Dakin,^^" and others, 

 however, found evidence that the liver cells may also reduce diacetic 

 to i3-oxybutyric acid, and it seems probable that this is the usual 

 direction of the reaction, which they have found to be produced by a 

 specific enzyme. Hurtley^^ concludes that the reduction of aceto- 

 acetic acid to oxybutyric acid is accomplished by the body under 

 ordinary conditions far more readily than the oxidation of oxj^butyric 

 to aceto-acetic acid. Marriot*^" gives the following scheme as indicat- 

 ing the normal path of fatty acid catabolism : 



d-oxj'butyric acid 

 Fatty acid >Butyric acid(?) > Aceto-acetic acid '\l-oxybutyri™acid 



(difficultly burned) 



The study of the utilization of the acidosis substances when injected 

 intravenously at accurately measured rates for considerable periods 

 by Wilder, ^^ furnishes conclusive evidence of the origin of /3-oxy- 

 butyric acid from acetoacetic acid. He found that normal dogs ex- 

 crete i3-oxybutyric acid when it is injected at the rate of 0.4 gm. 

 (0.0032 gm. molecule) of the sodium salt per kilo of body weight per 

 hour, but not with lower rates. Sodium acetoacetate was excreted 

 when injected in rates of 0.2 gm. (0.0016 gm. molecule) per kilo per 

 hour, and when injected at the 0.4 gm. rate it was excreted accom- 

 panied by /3-oxybutyric acid. Evidently, then, the acetoacetic acid 

 must be converted almost quantitatively into /3-oxybutyric acid. On 

 the other hand, acetoacetic acid did not appear in the urine when 

 larger quantities of /3-oxybutryic acid were injected, and hence it is 



59- Jour. Biol. Chem., 1909 (6), 373; 1910 (8), 105. 



60 Jour. Biol. Chem., 1914 (18), 241. 



61 Jour. Biol. Chem., 1917 (31), 59. 



