142 III. OXIDATION AND METABOLISM 



is given to the phlorhizinized dog in a sufficiently large dose to charge the 

 tissues with carbohydrate temporarily, a portion of this foodstuff is oxidized, 

 and the diabetic symptoms disappear. ^®^ Wierzuchowski^^^'^™ was the 

 first to observe that the dramatic improvement in physical condition noted 

 when glucose was given to a phlorhizinized dog was related not only to its 

 increased blood sugar level but also to the disappearance of the acidosis. 

 Acetonuria had vanished within four hours after the administration of glu- 

 cose, and the C02-combining power of the blood returned to normal within 

 this period. 



Goldfarb et al.^''^ reported that rats, fasted and phlorhizinized over periods 

 of one to four days, excreted ketone bodies varying in amount between 277 

 and 1760 mg. It was concluded that the production of the ketone bodies 

 closely approximated the theoretical yield based upon corrected factors for 

 the ketogenic and antiketogenic values of the foodstuffs oxidized. In a 

 later report, Goldfarb"^ arrived at similar conclusions, following an inves- 

 tigation of various species of the monkey family. 



(/) Alkalosis, Acidosis, and Ketosis. The ketone bodies are readily man- 

 ufactured in the body whenever it is necessary to combat alkalosis. Davies 

 and associates^'^^ were the first to note that, when alkalosis due to CO2 

 deficit produced by hyperventilation was present, acetonuria occurred. 

 This observation was confirmed by a number of workers. ^^^~^^^ 



Several investigators have reported on the ketogenic effect of an alkalosis 

 produced by the ingestion of an excess of alkali. Booher and Killian^^* 

 noted that abnormally large amounts of ketone bodies were produced in 

 human subjects as the result of an excessive administration of alkali or 

 because of the loss of HCl by vomiting. Butts and associates^" found that 

 an increased ketonuria over and above the minimal value found during 

 fasting in rats resulted from the administration of sodium bicarbonate. 

 The effect of alkali administration was much more pronounced in the female 

 than it was in the male animals. The studies of MacKay and co-workers, ^''^ 



368 H. J. Deuel, Jr., H. E. C. Wilson, and A. T. Milhorat, /. Biol. Chem., 74, 265-298 

 (1927). 



369 M. Wierzuchowski, J. Biol. Chem., 67, xlii (1926). 



370 M. Wierzuchowski, J. Biol. Chem., 68, 385-397 (1926). 



"1 W. Goldfarb, S. B. Barker, and H. E. Himwich, /. Biol. Chem., 105, 283-286 (1934). 

 3"W. Goldfarb, J. Biol. Chem., 116, 787-791 (1936). 



3" H. W. Davies, J. B. S. Haldane, and E. L. Kennaway, /. Phijsiol, 54, 32-45 (1920). 

 3'* H. Beumer and A. Soecknick, Z. Kinderheilk., 37, 236-241 (1924). 



375 L. E. Booher and J. A. Killian, Proc. Soc. Exptl. Biol. Med., 21, 528-529 (1924). 



376 J. B. S. Haldane, Lancet, 1924, I, 537-538. 



377 J. S. Butts, H. J. Deuel, Jr., and L. Hallman, Proc. Soc. Exptl. Biol. Med., 32, 

 898-899(1934-1935). 



378 E. M. MacKay, A. N. Wick, H. O. Carne, and C. P. Barnum, J. Biol. Chem., 138, 

 63-68 (1941). 



