Van Slyke and Meyer1 were able to determine directly amino-acids in the blood. Thus the absorption of 12 grams of glycocoll from the intestine of a dog caused an increase in the amino-acid content of the blood from 3.9 to 6.3 milligrams per 100 c.c. of blood volume. After giving 1000 grams of meat to a dog the amino-acid content of the blood doubled or more than doubled in a mesenteric vein, and the urea content also increased. There was almost as great an increase in the amino-acid content of the femoral vein as in the mesenteric, and therefore Van Slyke concludes that amino-acids are not largely retained by the liver.

Van Slyke and Meyer2 have confirmed the work of Folin and Denis in showing that the tissues absorb amino-acids with great avidity. The normal concentration of amino-acids in the tissues were found to be five to ten times that in the blood. Optimal figures are given as 80 milligrams per 100 grams of muscle, and 150 milligrams per 100 grams of liver. In one experiment the introduction into the vein of a dog of amino-acids derived from casein and containing 4.06 grams of nitrogen resulted after half an hour in an increase of amino-acids in the blood from 3.9 to 45.4 milligrams per 100 grams. This quantity would account for 5 per cent, of the total amount injected, and since 11 per cent, was eliminated in the urine it appears that the remainder or 3.41 grams of N must have been absorbed by the tissues.

Finally, it was shown by Van Slyke and Meyer3 and independently by Wishart4 that although the ingestion of meat in large quantity increases the amino-acid content of the blood, it does not increase that of muscle tissue. It is therefore probable that when nitrogen is retained in the organism it is not to an appreciable extent stored as digestion products, but rather in the form of protein (see p. 169). Such amino-acids as are not so synthesized are, therefore, destroyed as rapidly as they accumulate.

1 Van Slyke and Meyer: "Journal of Biological Chemistry," 1912, xii, 399. 2 Ibid., 1913-14, xvi, 197. 3Ibid., 1913-14, xvi, 231.

4 Wishart: "Journal of Biological Chemistry," 1915, xx, 535.

Van Slyke and Meyer1 conclude that absorbed amino-acids disappear rapidly from the liver, although their concentration in the muscle suffers no appreciable fall. The urea concentration in the blood increases. The liver de-saturates itself and in this way metabolizes superfluous protein.

On the other hand, Fiske and Sumner,2 in Folin's laboratory, after tying a ligature around the portal vein and hepatic artery of a dog, find that intravenous injection of amino-acids leads to as great a formation of urea as in a normal animal. They explain Van Slyke's results as indicating that the liver might rid itself of amino-acids as it does of glycogen without being of necessity involved in their destruction.

In this relation it may be added that Abderhalden3 showed several years ago that tryptophan was converted into kynu-renic acid as readily in a dog with an Eck fistula (see p. 451) as in one without.

The first actual isolation of an amino-acid from blood was reported by Abel4 at the International Physiological Congress held at Groningen in the summer of 1913. Alanin was found in considerable amount in a diffusate formed by dialyzing the blood during its continuous passage from an artery of a living animal through a system of tubes made of celloidin immersed in a saline solution, the blood then returning to the animal by a vein. This method of vividiffusion yields alanin in crystalline form. Histidin and creatinin may be determined by color reactions. Sugar, urea, ammonia β-oxybutyric acid, and lactic acid also diffuse from the blood in marked amounts.

1 Van Slyke and Meyer: "Journal of Biological Chemistry," 1913-14, xvi, 213.

2 Fiske and Sumner: "Journal of Biological Chemistry," 1914, xviii, 285.

3 Abderhalden, London, and Pincussohn: "Zeitschrift fur physiologische Chemie," 1909, lxii, 139. Consult also Mathews and Nelson: "Journal of Biological Chemistry," 1914, xix, 229; Taylor and Lewis: Ibid., 1915, xxii, 77.

4 Abel, Rowntree, and Turner: "Journal of Pharmacology and Experimental Therapeutics," 1913-14, v, 611.

Abderhalden1 worked with 50 and 100 liters of blood-serum and reports the presence of ten different amino-acids. Abel2 calls attention to the fact that secondary changes which may conceivably take place in shed and coagulated blood play no part in his method of vividiffusion, which separates diffusible substances from the circulating blood of living animals.

Van Slyke and Meyer3 report that free amino-acids do not disappear from the tissues on fasting, but, if anything, they tend to increase there.

These facts are interpretative of conditions in fasting. That amino-acids are produced in fasting is demonstrated in the cited instance of the salmon in which the protein of the genital organs increases at the expense of muscle protein. Thus Kossel4 estimates that a salmon weighing 9 kilograms deposits at breeding time in its testicles 27 grams of salmin containing 22.8 grams of arginin. Kossel calculates that metabolism of muscle protein during this time yields ample arginin to form the new salmin.