It is evident that the liver is not the only organ in which uricase converts uric acid into allantoin.

Wiechowski found that the allantoin excretion of the cat followed the same laws as obtain in the dog, and Hunter and Givens3 report that the extent and behavior of the allantoin excretion of the Wyoming coyote is practically identical with that of the dog.

Hunter and Givens4 state that the excretion of purin bases in the monkey greatly exceeds the elimination of uric acid, a condition which also appears in the horse, sheep, pig, and goat. For the monkey the percentage figures are:

3 Hunter and Givens: "Journal of Biological Chemistry," 1910-11, viii, 449.

4 Hunter and Givens: Ibid., 1914, xvii, 37.

When allantoin was given subcutaneously to the monkey 75 to 90 per cent, was recovered in the urine.

Hunter and Givens1 present the following table showing the relative purin content in the urines of various species of animals:

An extraordinary exception to the rule of oxidation of uric acid to allantoin in the dog was discovered by Stanley Benedict2 to be characteristic of the Dalmatian hound, or spotted coach dog. The urines of these dogs contain large amounts of uric acid. When uric acid is administered subcutaneously it is completely eliminated in the urine instead of being oxidized to allantoin, as would happen ordinarily in the dog. This is a peculiar racial anomaly.

1 Hunter and Givens: "Journal of Biological Chemistry," 1914, xviii, 403. 2 Benedict, S. R.: "The Harvey Lectures," 1915-16.

The urine of man is almost free from allantoin and the 10 to 15 milligrams which Wiechowski found therein may be accounted for as originating from traces of the substance found in common foods.1

Loewi2 showed that the ingestion of the same amount of nucleoprotein-containing food by different people resulted in the excretion of the same increased quantity of uric acid in the urine, and he surmised that the uric acid which was produced in the human being was not oxidized. Confirmation of this idea was given by the discovery of Soetbeer and Ibrahim3 that the subcutaneous injection of uric acid in man led to its complete elimination in the urine.

For a long time this viewpoint was overshadowed by experiments which showed only a moderate recovery of uric acid in the urine when purin bases in measured quantities were given to human beings. These results, which were interpreted to be due to the oxidation of the purins through the uric acid stage, are now attributed to their non-absorption or their putrefaction in the intestinal tract.

Wiechowski4 found that allantoin injected subcutaneously is completely eliminated in human urine, which is normally free from it. He also found that human tissues have no power to oxidize uric acid; it can always be completely recovered. Therefore the human organism lacks the enzyme uricase.

In concordance with these results Umber and Retzlaff5 find that if uric acid be dissolved in piperazin and be injected into a healthy human being, between 80 and 95 per cent, may be recovered in the urine; also Levinthal6 injected 1 gram of xanthin dissolved in piperazin into the vein of a healthy-human subject, and concluded that, in all probability, all the xanthin which reached the metabolic circulation was completely eliminated without the rupture of the purin nucleus, the larger part being oxidized to uric acid and only a small remainder passing unchanged through the organism.

1 Ackroyd: "Biochemical Journal," 1911, v, 400.

2 Loewi: "Archiv fur exp. Path, und Pharm.," 1900, xliv, 1.

3Soetbeer and Ibrahim: "Zeitschrift fur physiologische Chemie," 1902, XXXV, I.

4 Wiechowski: "Archiv fur exp. Path, und Pharm.," 1909, lx, 185. 5Umber and Retzlaff: "Verhandlungen des 27ten Congresses fur innere Medizin," 1910, Sec. Ill, p. 436.

6Levinthal: "Zeitschrift fur physiologische Chemie," 1912, lxxvii, 259.

Finally, the experiments of Thannhauser and Bommes1 deserve attention. When adenosin and guanosin were administered subcutaneously to normal men, between 75 and 82 per cent, of the purin bases contained in them were eliminated in the urine of the following twenty-four to forty-eight hours in the form of uric acid. These water-soluble purin-glucosids, adenosin and guanosin, are undoubtedly intermediary metabolites of nucleic acids.

The synthetic origin of purins in metabolism has been recognized since the work of Miescher (see p. 82). Kossel2 showed that purins developed in the incubated egg, which when newly laid is free from them (see also p. 371).

It has been made clear that in mammals the purins may be derived from ingested nucleoproteins, but this cannot be the only source, since purins are found in the urine during starvation and on a diet free from purins. This indicates a constant production of these substances in metabolism. Uric acid and purin bases from this source have been termed endogenous by Burian and Schur, in contradistinction to those which are eliminated after the ingestion of nuclem-containing food, which are called exogenous.

1 Thannhauser and Bommes: "Zeitschrift fur physiologische Chemie," 1914, xci, 336.

2 Kossel: Ibid. 1886, x, 248.