422 JOSEPH H. PKATT 



Ascoli and Izar claim that they have experimental evidence that synthesis 

 occurs, but their work has been refuted by Spiers and Wells. Synthesis 

 of nucleic acid occurs in mammals, but synthesis of uric acid is not only 

 improved, but its existence is unlikely. Hence in the building up of the 

 purin molecule in the body the process probably does not pass through a 

 uric acid stage, but occurs in some way yet unknown. 



The Source of Uric Acid in the Urine 



With a person on a purin free diet the uric acid in the urine must 

 come from his own tissues, either from broken down cell nuclei or from 

 living cells as a product of nuclear metabolism. In any case the uric acid 

 is endogenous in origin. For many years it was generally held that this 

 output of endogenous uric acid was constant for the individual. Burian 

 and Schur(6) and Siven announced simultaneously in 1900 that with the 

 individual on a purin free diet there was very little fluctuation from day 

 to day in the uric acid excretion. Their observations were confirmed 

 among others by Kaufmann and Mohr in Germany, Hall (a) in England, 

 and in this country by Rockwood, and MacLeod and Haskins. This 

 conclusion that the output of uric acid was constant was drawn from the 

 study of too few individuals and has been found to be erroneous. It is 

 now known that the character and quantity of the purin-free diet may 

 influence greatly the output of uric acid. Folin(c) found that on a cream 

 and starch diet about one-half as much uric acid was excreted as on purin 

 free milk and egg diet and his observations were confirmed by Jackson 

 and Klackfan. Leathes(a) also found that on a low protein diet the uric 

 acid excretion is less than on a more normal one. 



While in some individuals the output of uric acid is remarkably con- 

 stant on a purin free diet, in others fluctuations amounting to 15 per cent 

 or 20 per cent occur. Ackroyd(a) states that a fluctuation as great as 

 0.11 gram of uric acid is not abnormal. Examinations of the literature 

 show wider variations than this in normal subjects. In Mallory's(a) nor- 

 mal case the maximum fluctuation in a period of 34 days was 0.20 gram, 

 and a subject studied by Mendel, Underhill and White exhibited a varia- 

 tion of 0.19 gram in four days on a purin free diet. 



Host (a) in a recent study of 17 normal subjects found that with a fixed 

 non-protein diet the uric acid output in a few subjects was constant, while 

 in the majority it was irregular and showed variations from day to day 

 up to 80 per cent. If the caloric value is increased or decreased consid- 

 erably the uric acid output is always changed in the same direction. The 

 change of uric acid output is greater when the amount of calories is varied 

 by means of protein than by nitrogen free food elements. If the calories 

 are kept constant, but the food protein changed beyond a certain minimum 



