526 AB.\OiiUALlTlE>i IS METABOLISM 



= c/ . "We know that the liver is able to accomplish the con- 



,NH, 



\nil • 



version of amino-aeids to urea, for it has been experimentally shown 

 that if leucine and glycocoll are passed through the vessels of the iso- 

 lated liver they disappear in part, while an increased amount of 

 urea escapes from the hepatic veins. It is probable that the liver 

 is the chief site of urea formation, but it is also probable that urea 

 can be formed in other organs. We do not know, however, the in- 

 termediate steps by which the amiuo-acids of the protein molecule are 

 converted into urea. It has been repeatedly shown that urea can be 

 formed from ammonium salts of organic acids (including ammonium 

 carbonate), and ammonia is a constant product of autolysis, being 

 characteristically more abundant as a product of autolytic proteolysis 

 than as a product of tryptic proteolysis ; therefore, one of the ante- 

 cedents of urea is probably ammonia, which is somewhat toxic and 

 especially hemolytic." Another antecedent of urea is ammonium car- 

 bamate, which stands in structure intermediate between urea and am- 

 monium carbonate, as shown by the following graphic formulae : 



,0H .0 — NH, .NH. .NH. 



0=C< 0=C< 0=C< 0=C< 



(carbonic acid) (ammonium carbonate) (ammonium carbamate) . (urea) 



That ammonium carbamate is possibly an important precursor of 

 urea has been shown particularly through the results of studies of 

 dogs with Eck's fistula,*' which consists of a fistula between the portal 

 vein and the inferior vena cava, the blood from the portal system 

 then passing directly into the general circulation without first passing 

 through the liver. In such animals the urine becomes poor in urea 

 and relatively rich in ammonium carbamate. At the same time, the 

 dogs show severe symptoms of intoxication from which they die, and 

 which are similar to the symptoms that follow intravenous injection 

 of ammonium earl)anmte. Ammonium carbamate, being a substance 

 of considerable toxicity ^ when free in tlie bh)()d, it has, therefore, 

 been quite widely considered that it may be an important factor in 

 the production of uremic symptoms. On the other hand, it seems 

 most pr()ba])]e that the condition of uremia does not depend upon one 

 but upon many various and varying su])stances, especially as Hawk '^ 

 found that sodium carbamate did not produce uremic symptoms in his 

 Eck fistula dogs, while Liebig's extract did." Clinically the symptoms 



5 Concerning the toxicity of iunmoniuiii sails sco IJacliford and Craiio. 'Medical 

 News, 1902 (81), 778. 



6 See Hahn, Masson, Xciicki, and rawlow, Arcli. f. cxp. l*alli, u. riiarm.. 1S0.3 

 (32), 161. 



7 See Bickcl, "Exp. ITntersucli. iibor Cliolaciiiic," W'icsliadcii. 1000. 



8 Amor. .Tour. Pliysi(d., 1008 (21), 2(10. 



Fisclilcr l»(di('ves tlie iiiloxicatioii wliicli occurs after fcc(liii<r meat to Eck 

 fistula dofis to be an alkalosis, probably from Nil., salts (Deut. Arch. klin. Med., 

 lit 11 (104), .300). 



