URIC ACID AND THE PURINE BODIES 647 



be produced as a result of the combination of amino-malonic acid with 

 urea, the amino-malonic acid being produced by condensation of hydro- 

 cyanic-acid molecules: 



3 HCN - H 2 N- CH(CN) 2 + CO(NH) 2 -^ NH - CO 



I ! 



CO CNH 2 



! I! 



NH - CNH 2 



(hydrocyanic (amino-malonic (urea) (oxy-diamino-pyrimidine) 

 acid) nitrile) 



Another possible source of pyrimidine is the oxidation of arginine to 

 guanidine-propionic acid, which then condenses to form ammo pyrimi- 

 dine. 



Purine synthesis undoubtedly occurs in the mammalian body, but it 

 is difficult to recognize in metabolism investigations because it is a slow, 

 continuous process. The probability of its occurrence, however, is indi- 

 cated by such results as those described on page 614, in which increase 

 in purine excretion is observed after varying the intake of food, even 

 when this is itself entirely free from purine substances. Whether or not 

 changes in the activity of purine synthesis occur in conditions of disease 

 is a question which awaits investigation. 



The Influence of Various Physiologic Conditions, of Drugs, and of 

 Disease on the Endogenous Uric-acid Excretion. Muscular exercise was 

 thought by Burian to cause an increased excretion of uric acid, from 

 which he drew the conclusion that the hypoxanthine present in compara- 

 tively large amount in muscular extract, or its precursor, inosinic acid, 

 must be an important source of endogenous uric acid. Other observers 

 (Leathes, etc.) have found that strenuous exercise causes a distinct in- 

 crease in uric-acid excretion, which, however, is much less marked on 

 repetition of the same kind of exercise on the next day. If some new 

 kind of muscular work is performed, another increase in uric acid will 

 result. There are still other investigators who deny that muscular work 

 has. any influence on uric-acid excretion. 



It has been observed by several investigators that the endogenous 

 purine excretion is distinctly higher during the waking h'ours than during 

 sleep. This can not be shown to depend on variations in the urinary 

 function, and since it is decidedly doubtful whether ordinary muscular 

 activity has any influence, the diurnal variation is most difficult to 

 account for. The endogenous excretion in man is not the same for 

 different individuals, even when calculated for the same body weight; it 

 varies between 0.12 and 0.20 per cent purine nitrogen in an adult man. 

 It remains remarkably constant for a given individual from time to 

 time, being unaffected by moderate degrees of variation in the amount 



