TRIGLYCERIDES AND FATTY ACIDS 143 



demonstrated, in the case of the rat, that acidosis reduces ketonuria while 

 alkalosis augments this condition. This is explained on the basis that 

 acidosis produces an antiketogenic effect due to increased protein catab- 

 oUsm, which results in an increased glucose formation. Alkalosis, on the 

 other hand, was beheved to have the opposite effect on this process. In the 

 case of man, Beumer and Soecknick'^* and Porges and Lipschiitz'''^ demon- 

 strated that fasting ketonuria is exaggerated by the ingestion of alkali, 

 while Adlersburg^^" noted that ketosis of fasting was decreased by the 

 ingestion of acid ammonium phosphate. In the light of the later experi- 

 mental work, it seems probable that the excessively high levels of ketonuria 

 reported in diabetic subjects in pre-insulin days may have been partly 

 caused by the extremely high dosages of alkali employed. According to 

 Lusk,^'- dosages of sodium bicarbonate as high as 200 g. per day were in 

 common use. This subject has been discussed further in the early sec- 

 tion on diabetes mellitus (see page 122). 



Although the administration of acid-producing salts such as NII4CI 

 results in a decrease of ketonuria in the intact animal, just the opposite 

 effect has been reported in isolated tissues. Recknagel and Potter, ^^^ 

 using rat liver homogenates supplemented with ATP, confirmed the earher 

 reports of Annau^*^ obtained with liver mince, and of Edson^** with liver 

 shces, which demonstrated that ammonium chloride exerts a ketogenic 

 effect. It is suggested that the following steps are involved: (1) A 

 preliminary vigorous reductive amination of a-ketoglutaric acid takes place ; 

 (2) because of the interruption in the Krebs cycle at the stage of the oxida- 

 tion of a-ketoglutarate to succinate, the system fails to supply sufficient 

 oxaloacetate for citric acid condensation; and (3) since the preferential 

 pathway to citric acid is no longer available, the metabohsm of ketone body 

 precursors is shunted in the direction of acetoacetate formation. 



(^ Experimental Ketonuria in Rats. The rat is an animal which, under 

 ordinary conditions, produces a ketonuria of such low intensity as to render 

 it entirely valueless for studies in this field. Thus, Levine and Smith^^^ 

 reported that the total ketonuria for a four-day period calculated for a 250 

 g. rat was 16.9 mg. The total ketone excretion for a group of nine rats 

 with an average weight of 224 g. varied between 2.3 and 19.2 mg. Cori 

 and Cori^^^ observed that rats excreted 6.2 mg. per 100 g. rat per day in 



*" O. Porges and H. Lipschiitz, Naunyn-Schmiedeberg's Arch, exptl. Pathol. Phar- 

 makol., 97, 379-385 (1923). 



^ D. Adlersburg, Biochem. Z., US, 527-532 (1923). 



Ml R. O. Recknagel and V. R. Potter, /. Biol. Chem., 191, 263-275 (1951). 



882 H. Levine and A. H. Smith, /. Biol. Chem., 75, 1-22 (1927). 



3" G. T. Cori and C. F. Cori, J. Biol. Chem., 72, 615-625 (1927). 



