644 METABOLISM 



from the organism itself. As to what this may be, it is impossible to 

 say. It may be associated with the work of the gastric and intestinal 

 glands, which recalls the interesting suggestion, originally made by 

 Horbaczewski, that ingested substances increase the excretion of uric 

 acid by causing a leucocytosis, the purine being derived from the nucleic 

 acid set free when the leucocytes become broken down. That this is 

 not the correct explanation, however, is indicated by the fact that in- 

 gested substances that give rise to an increased number of leucocytes 

 affect the excretion of uric acid during the period the leucocytes are 

 present in the blood, and not after they have disappeared, which would 

 have to be the case were the uric acid a product of purine substances 

 liberated by their breakdown. This would indicate that the purine sub- 

 stance is a metabolic product of the living leucocytes and not a break- 

 down product of those that are dead. It should be noted that the increase 

 in the postprandial uric-acid excretion occurs earlier than that of urea. 



The most pressing question concerns the origin of the endogenous 

 purines. Uric acid is the purine with which we are most concerned in 

 the case of man, and chemistry shows us that it may be produced either 

 by the oxidation of the lower purines namely, of those which are the 

 constituent parts of the nucleic-acid molecule or by a synthesis of two 

 urea molecules with a carbon residue containing three carbon atoms. 

 There are consequently two sources from which the endogenous purine 

 excretion in man may be derived : (1) synthesis of two urea molecules, 

 and (2) oxidation of the lower purines. 



We will consider first the possibility of synthesis. In birds and 

 reptiles practically all the nitrogen is excreted in the form of uric acid, 

 and it is easy to show that this has been produced in the organism by 

 the synthesis of urea with carbon-rich residues, occurring mainly in the 

 liver. Minkowski found that by removing the liver from geese, which 

 is a comparatively simple operation on account of an anastomotic vein 

 between the portal and the renal veins, the uric acid in the urine became 

 very markedly decreased and ammonium lactate took its place (page 

 618). Since we know that ammonium in the animal body is ordinarily 

 converted into urea, we may conclude from this observation that some- 

 thing has occurred to prevent the synthesis of urea into uric acid. In 

 confirmation of this conclusion it was subsequently found that, if am- 

 monium lactate was added to the blood perfused through the isolated 

 liver of the goose, uric acid was produced in the perfusion fluid.* Fur- 

 thermore, when birds and reptiles are fed with ammonium salts or 

 with the degradation products of protein, there is an increase in the ex- 



*The reason for the formation of this relatively insoluble metabolite in place of the soluble urea 

 is connected in some way with the fact that birds and reptiles do not take such large quantities 

 of water with their food as other animals. 



