In the first days the amount of protein metabolized depends upon the two factors, the glycogen content of the individual and the quantity of protein ingested before the starvation period. The influence of the first factor was shown by Prausnitz.1 Fifteen individuals (mostly medical students who were taking a course of instruction in the laboratory) fasted for sixty hours. The first day's urine was collected beginning after twelve hours of fasting. The second day's urine contained in 12 cases more nitrogen than that of the first day of starvation. The lower protein destruction on the first starvation day must have been due to the continued use of sugar from the glycogen supply. It is known that the combustion of sugar considerably reduces the protein metabolism, so the second day and not the first of starvation should be taken as the basis of the fasting protein metabolism.

This influence of glycogen metabolism on that of protein during the first and second days of fasting is beautifully shown in experiments by Benedict2 (see also p. 89).

1 Prausnitz: "Zeitschrift fur Biologie," 1892, xxix, 151. 2 Benedict: "The Influence of Inanition on Metabolism," Carnegie Institution of Washington, 1907, Bulletin No. 77.

Influence Of Glycogen Metabolism On That Of Protein In Fasting. Weights In Grams

It is evident that where there is an abundant glycogen reserve the protein metabolism is reduced by the oxidation of carbohydrates, but where there is little glycogen to draw upon the protein metabolism is high even on the first day of starvation.

The second factor, or the influence of the previous meat ingestion, is especially dominant in dogs. (For effect on man see p. 275.) Voit1 fed a dog weighing 35 kilograms with different quantities of meat and noticed the effect on urea elimination during subsequent starvation. The results were as follows:

Influence Of Previous Diet On Urea Elimination In Starvation

1 Voit: "Zeitschrift fur Biologie," 1866, ii, 307.

It is evident from this that on the sixth day of starvation the urea elimination was the same in all cases, or about 13 grams of urea per day. Voit deducted the 12 grams from what he had found for the first days and obtained the grams of urea which were derived from the previous food, as follows:

Urea Elimination In Starvation Attributable To Previous Diet

The amount of extra protein metabolism is seen from the above to be directly dependent on the previous feeding, a common level being reached in all cases on the fifth day of fasting.

These experiments led Voit to differentiate between "circulating protein," which could be absorbed, carried to the tissues, and burned, and "organized protein," the more resistant living protein of the tissues themselves. Voit1 stated that in metabolism the lifeless protein furnished to the cells by the blood was used in preference to the living organized tissue protein. He quoted Landois' experiments, which show that after producing an artificial plethora through injection of blood, the serum proteins are readily burned and their nitrogen eliminated in the urine, while the red blood.cells containing the organized protein are only slowly destroyed. If serum alone be transfused, its protein is rapidly destroyed.2

1 Voit: "Handbuch der Ernahrung," 1881, p. 300. 2 Forster: "Zeitschrift fur Biologie," 1875, xi, 496.

Even in starvation there is evidence of "circulating protein" as food for the tissues. Thus Miescher showed that the salmon, after entering the Rhine from the sea, virtually starves. Yet the genital organs of both male and female develop greatly, this being at the expense of the muscles, which may lose 55 per cent, of their weight. This protein must have been carried to the various parts of the body in the circulating blood-stream. Miescher finds no indication of any destruction of muscle-fibers in this process of emaciation (see p. 249). It is interesting in this connection to note that A. R. Mandel1 has been able at a pressure of 300 to 350 atmospheres acting on lean meat seventy-two hours old to press out a fluid containing 44 per cent, of the protein present in the fibers, and this without visible change from the normal histologic appearance of the muscle.

It seemed quite possible that in ordinary starvation protein from muscle and other tissues passed to the blood and was carried to all the organs as circulating protein for the nutrition of their cells.

The great work of Kossel, Hofmeister, and Emil Fischer has taught that the essential composition of protein is a structure formed of chains of amino-acids. Fischer has constructed artificial peptids, bodies in which two or more amino-acids are united together. For example, glycyl-glycin is formed by the' union of two molecules of glycocoll with the loss of water, as follows:

Fischer has hung together eighteen of these radicles in an octodecapeptid containing four leucin and fourteen glycocoll molecules and being 1-leucyl-triglycyl-l-leucyl-triglycyl-l-leucyl-octoglycyl-glycin.

1 Mandel: Unpublished work from the Munich Clinic of Prof. Fr. Muller.

This forms a body akin to pepton. The high molecular complexes called proteins, which constitute the basis of our being, are, after all, separable into simple chemical compounds. In the larger molecule these amino-acids are chained together, even as in structural framework various iron beams are riveted together. Digestive proteolysis or internal metabolism rends the higher structure of the molecule and leaves its individual supports, the amino-acids, open for further disintegration.1