080 METABOLISM 



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



CO CNH 2 



! II 



NH - CNH 2 



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

 acid) nitrile) 



Another possible source of pyrimidine is the oxidation of arginine to guanidine-pro- 

 pionic acid, which then condenses to form amino pyrimidine. 



Purine synthesis undoubtedly occurs in the mammalian body, but it 

 is not easy to recognize for its occurrence is difficult to detect in metab- 

 olism investigations; it is a slow, continuous process. The probabil- 

 ity of its occurrence, however, is indicated by such results as those 

 described on page 648, 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 Physiological 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, 62 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 hours 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 

 of food taken, provided this be purine-free; when, however, the amounts 

 are extremely variable, changes are produced (see page 648). 



In disease, fever causes an increased excretion. This has been most 

 clearly shown by Leathes, 62 who took a large enough dose of antityphoid 



