278 ROLLIN T. WOODYATT 



inents caii not now be made. In December, 1910, on the basis of chemical 

 studies by Ciamician and Silber, and test tube experiments with acetoacetic 

 acid, I suggested a certain type of reaction as the basis of "Antiketogenesis" 

 in which one molecule of acetoacetic acid would react with one molecule 

 of an alcohol or glucose. Zeller, working with normal individuals on ample 

 diets consisting of carbohydrate and fat with very low protein contents, 

 shifted the proportions of fat and carbohydrate without changing the total 

 calories and saw acetone appear when the ratio of carbohydrate calories 

 fell below 10 per cent of the total; that is, when the ratio of fat to car- 

 bohydrate in the diet in grams was about 4 to 1. Recalculating Zeller's 

 experiments, Lusk estimated the relative quantities of sugar and higher 

 fatty acid that might have been oxidizing together in the body. Allowing 

 for the formation of sugar from the glycerol of the fat, and the glucose 

 from the protein catabolized and for some glucose from glycogen, but not 

 for ketogenic amino-acids from protein, Lusk suggested that possibly one 

 triose molecule was necessary for the complete oxidation of 1 of higher 

 fatty acid that is, 1 molecule of glucose to 2 of higher fatty acid. Recently, 

 Palmer has repeated experiments of the Zeller type in diabetics and ob- 

 tained results that appear to be harmonious. P. A. Shaffer (c) has worked 

 with test tube experiments and with diabetic individuals in which he con- 

 ducted metabolism studies, including observations of the respiratory quo- 

 tient at the time acetone first appeared. Shaffer calculated the ketogenic 

 acids of protein on the basis of the quantities of leucin, tyrosin and phenyl 

 alanin found in 100 grams of ox muscle protein by Osborn, assuming that 

 each molecule of these known acetone formers may yield 1 molecule of 

 acetoacetic acid or its equivalent. As a result of his work, Shaffer sug- 

 gests that one molecule of glucose is necessary for the complete oxidation 

 of 1 molecule of acetoacetic acid or 1 molecule of any higher fatty or 

 amino-acid that yields 1 molecule of acetoacetic acid (or equivalent). 



The molecular weight of glucose being 180, of oleic acid 284, of pal- 

 mitic acid 256 and the average of the two acids 270, the ratio found by 

 Shaffer, if expressed in grams, would be 1.57 or 1.42, average 1.5 grams 

 higher fatty acid to 1 gram glucose. Working with diabetic patients on 

 maintenance diets under conditions that made it probable that the pro- 

 portion of foodstuffs in the diets corresponded fairly with those catab- 

 olized in the body, and estimating the glucose and fatty acid as herein- 

 after indicated, Woodyatt also observed at the time acetone appeared, 

 ratios varying about 1.5 with considerable frequency. Accordingly even 

 though it may prove necessary to revise the figure as data accumulate, 

 it would seem that for clinical purposes and for the time being one would 

 make no gross error in assuming that as a general rule the ratio of higher 

 fatty acids to glucose which, if exceeded for a sufficient length of time, 

 will lead to acidosis is over and under 1.5 to'l (in grams). Higher ratios 

 without acetonuria are not rare but, when observed, the question arises as 



