After the ingestion of protein in the normal organism this sugar early becomes available and may be oxidized before the nitrogen belonging to it is eliminated, or if the sugar be formed in excess, it may be stored as glycogen in the liver and muscles of the body for subsequent use. In this way it is obvious that at least half the energy in protein may be independent of the curve of nitrogen elimination, but may rather act as though it had been ingested in the form of carbohydrate. This will be explained in the next chapter. It is therefore evident that this carbohydrate, which is early supplied in the breaking down of protein, may distribute its energy according to the requirement of the cells as long as it lasts. This is apparently the principal cause of the comparative evenness of the carbon dioxid excretion as contrasted with the great irregularity of the nitrogen elimination after protein ingestion.

1 Berger: Inaugural Dissertation, Halle (Nebelthau), 1901; cited from Maly's "Jahresbericht uber Thierchemie," xxxi, 848.

Pfluger who, longer than any physiologist, denied the validity of any existing proof that glucose arose from protein, was in his old age ultimately convinced by the following experiments. He1 found that when dogs were allowed to fast for ten days and then made diabetic by an injection of phlorhizin the glycogen of the liver amounted to 0.1 per cent, and of the muscles to 0.2 per cent. If dogs reduced to this condition were given large quantities of codfish (which contains only 0.03 per cent, glycogen) the glycogen content of the liver averaged 6.5 per cent., and in one case rose to 9.9 per cent., and the glycogen content of the muscle averaged 1 per cent. Since fat ingestion was without effect upon the glycogen store, Pfluger acknowledged the origin of glucose from protein.

It must be borne in mind that it is not very long ago that it was perfectly permissible to think of protein as a complex containing many glucose molecules existing in a highly polymerized condition and combined with nitrogen-containing radicles, of which glycocoll, leucin, and tyrosin at least were readily obtainable as cleavage products. Such a molecule explained the older conceptions of protein metabolism. The work of Hofmeister, Kossel, and Emil Fischer first gave a true insight into the composition of the protein molecule. One must know the life history of sixteen amino-acids in order to be familiar with the metabolism of protein. Though the extension of knowledge may have been at the cost of simplicity, yet order is being wrought out of apparent complexity. It is often difficult for an older generation to think in terms of the knowledge of a new. The author's father was a student at Heidelberg at the time when the modern chemical formulae were introduced, when H - O became H20, and he recalled the distracted exclamation of one of the university professors, "Ach Gott! wie kann man so lernen!"

1 Pfluger and Junkersdorf: "Pfluger's Archiv," 1910, cxxxi, 201.

The intimate knowledge of the behavior of the amino-acids within the body may be studied by a variety of means.

1. The direct removal in the urine of certain of the amino-acids, such as glycocoll and cystein, or the removal of slightly changed products, such as homogentisic acid from tyrosin and kynurenic acid from tryptophan.

2. The determination in the urine of a dog made diabetic by phlorhizin of the quantity of "extra glucose" eliminated after the ingestion of certain amino-acids, and the determination of an increase in the quantity of β- oxybutyric acid after the administration of other amino-acids under like conditions.

3. The results of experiments in which an amino-acid is added to warmed oxygenated blood and this perfused through a surviving liver, subsequent analysis of the blood revealing any chemical change which the material might have undergone.

It should be remembered that when amino-acids are ingested the resulting nitrogen increase in the urine is entirely due to urea.1 The same is true of the dipeptid glycyl-glycin2 (see p. 75). It is believed that the deamination of an amino-acid results in the formation of ammonia, which, becoming ammonium carbonate, may be converted into urea. Yet experiments in vitro have failed to demonstrate this action. Gertrude Bostock3 found that the liver and intestinal mucosa failed to deaminize alanin. Levene and Meyer4 find that leukocytes and kidney tissue do not deaminize glycocoll, alanin, aspartic acid, and leucin. Griesbach and Oppen-heimer5 are of the same opinion. Thus the characteristic biologic reaction of deamination is effected through the activity of living tissue cells. Special enzymes are nowhere in evidence.

For the understanding of the biochemic relations of the various amino-acids it seems desirable to present as briefly as possible the laws governing their fate in the organism.1

1 Levene and Kober: "American Journal of Physiology," 1909, xxiii, 324.

2 Levene and Meyer: Ibid., 1909-10, xxv, 214. 3 Bostock: "Biochemical Journal," 1911, vi, 48.

4 Levene and Meyer: "Journal of Biological Chemistry," 1913, xv, 65; 1913-14, xvi, 555.

5 Griesbach and Oppenheimer: "Biochemische Zeitschrift," 1913, lv, 329.