UREA. 907 
cirrhosis; the ammonia is usually accompanied by lactic acid. 1 In acute 
yellow atrophy there is besides a considerable amount of leucine and 
tyrosine. When carbonate of ammonia is administered to mammals, the 
excretion of ammonia is not increased in the urine, but urea is formed 
in proportion to the amount of ammonium carbonate ingested. 2 
It is possible that, as Drechsel 3 supposes, carbamate of ammonia may be 
the immediate precursor of urea, the carbonate being first converted into 
carbamate and then into urea. By elimination of one molecule of water, 
carbonate of ammonia forms carbamate, and by elimination of a second 
molecule, urea. 4 
/0(tfH 4 ) /NH 2 /NH 2 
c=o c=o c=o 
\0(NH 4 ) \0(NH 4 ) \NH 2 
(carbonate of ammonia) (carbamate of ammonia) (urea) 
When chloride of ammonia is administered with the food in herbivora 
(rabbits), the whole of the ingested ammonia appears as urea in the urine, 
but in carnivora and in man some of the ammonia is excreted in the urine. 5 
The difference is due to the fact that the inorganic salts of the food of 
herbivora contain an excess of potassium carbonate. This takes the hydro- 
chloric acid from the chloride of ammonia, and carbonate of ammonia is 
formed, which is readily converted into urea. But when there is an excess of 
proteid in the diet, sulphuric acid is formed by oxidation, and this combines 
with any bases present, so that the ammonia is not set free from the hydro- 
chloric acid, and the chloride of ammonia passes unchanged (Bunge). In 
fasting dogs all the ammonia administered may be recovered from the urine. 
It is obvious that the formation by synthesis of the neutral substance 
urea from the alkaline salt, carbonate of ammonia, which is formed in the 
metabolism of proteid, is a protection from the deleterious effects which 
might otherwise ensue from too high an alkalinity of the circulating fluid 
and urine. 
The presumption, therefore, undoubtedly is, that under ordinary 
circumstances the ultimate transformation of the products of nitro- 
genous metabolism takes place under the influence of the hepatic cells. 7 
1 For references consult Bunge's "Lectures," pp. 327 and 345; also Neumeister, 
"Lehrbuch," S. 315. 
2 Hallervorden (with Schmiedeberg), Arch. f. cxpcr. Path. u. Pharmakol., Leipzig, 
1880, Bd. xii. S. 237 ; Feder and E. Yoit, Ztschr.f. Biol., Munehen, 1880, Bd. xvi. S. 177. 
Feder and Voit found that acetate of ammonia also forms urea. The same thing was 
determined for citrate of ammonia by Lohrer, with Buchheim (Diss., Dorpat, 1862). This 
is the reason why citrate of ammonia does not, like citrate of potash, make the urine 
alkaline. Both citrates are converted into carbonates in the body, but the carbonate 
of ammonia becomes transformed into the neutral urea, while the carbonate of potash 
passes as such into the urine. 
3 Ber. d. k. sachs. Gesellsch. d. JFisscnsch., 1875, S. 171 ; Journ. f. prakt. Cliem., 
Leipzig, 1875, N.F., Bd. xii. ; 1877, Bd. xvi. ; 1880, Bd. xxii. ; Arch. f. Physiol., Leipzig, 
1880, S. 550. 
4 Hoppe-Seyler {Ber. d. deutsch. chem. Gesellsch., Berlin, 1874, Bd. vii. S. 34) and 
Salkowski {fientraibl. f. d. med. ITissensch., Berlin, 1875, S. 913; and Ztschr. f. physiol. 
Chem., Strassburg, 1877, Bd. i. S. 26) regard it as probable that cyanic acid maybe the 
immediate precursor of urea, wdiich is readily formed from eyanate of ammonia. But the 
evidence in favour of this supposition is by no means sufficient, whereas that in favour 
of ammonium carbonate (and carbamate) being the precursor, is very strong. 
5 v. Knieriem, Ztschr. f. Biol., Munehen, 1874, Bd. x. S. 263; Salkowski, Ztschr. f. 
phvsiol. Chem., Strassburg, 1897, Bd. i. S. 1. 
6 Feder, Ztschr.f. Biol., Munehen, 1877, Bd. xiii. S. 256. 
7 Richet has shown that a urea-forming ferment can be precipitated by alcohol from 
aqueous extract of liver (Compt. rend. Soc. de biol., Paris. 1894, p. 525). 
