Thanks especially to the work of Folin,1 these data are now apparently at hand, and the (acta which he has accumulated with painstaking care seem destined to throw additional light upon our conception of proteid metabolism. It will be remembered that in the breaking down of proteid the great bulk of its contained nitrogen is eliminated in the form of urea. Ill addition, a certain smaller amount, of nitrogen is excreted in the forms of creatinin and uric acid. As we have seen, the total output of nitrogen, which meaa-ures the extent to which proteid is decomposed in the body, varies with the intake of proteid food; but it is found that the proportion of nitrogen excreted in the forms of urea and uric acid varies with the extent of the metabolism. In other words, quantitative changes in the daily proteid katabolism are accompanied by pronounced changes in the distribution of the excreted nitrogen. Let us take a single illustration from Folin's results; the case of a healthy man who on one day - July 13 - consumed a proteid-rich diet, and on the other day - July 20 - was living on a diet containing only about 1 gram of nitrogen. The composition of the excretion through the kidneys on these two days is shown in the following table:

1 Otto Folin: Laws Governing the Chemical Compositionof Urine. American Journal of Physiology, vol.. 13, p, 66. A theory of Protein Metaboliim. Ibid., vol. 13, p. 117.

Here we see, as would be expected, that on the high proteid diet, there was a large excretion of total nitrogen and of urea; while on the low proteid diet, nitrogen and urea were correspondingly diminished. The point to attract our attention, however, is the marked difference in the percentage of urea-nitrogen in the two cases; a difference which amounts to about 26 per cent. A similar difference is to he noted in the percentage of uric acid-nitrogen. Lastly, it is to be observed that in spite of the great difference in the extent of metabolism on the two days - an excretion of 16.8 grams of nitrogen, as contrasted with 3.6 grams - the amount of creatinin-nitrogen is essentially the same. Polin finds that these peculiarities in the percentage distribution of excreted nitrogen hold good in all cases where there is this wide divergence in the amount of proteid katabolized, and, further, that there is a gradual and regular transition from the one extreme to the other. He Bees in these results evidence that there are in the body two forms of proteid katabolism, essentially independent and quite different. One kind is extremely variable in quantity, while the other tends to remain constant. The variable form has its own particular kind of waste products, of which area is the chief- The constant katabolism. on the other hand, is largelyrerjre,-senteTl by creatinin and to a lesser degree by uric acid. The more the total katabolism is reduced, the more prominent become creatinin and uric acid, products of the constant katabolism; while urea, as chief representative of the variable katabolism, becomes less conspicuous. Folin suggests the term endogcnout or tissue metabolism for the constant variety, while the variable form he would name exogenous or interne diate mgfolviliam.

Iu these suggestions we have not theory only, but a number of very important facts which plainly must have some significance. Take, for example, the excretion of creatinin. It is a characteristic nitrogenous waste product, but its elimination from the body is wholly independent of quantitative changes in the total amount of nitrogen excreted. In other words, the amount of creatinin elim. inated is a constant quantity for a given individual under ordinary conditions, no matter how great the variation in the amount of proteid food, provided no meat is eaten Meat must be avoided in testing this point, since meat contains a certain amount of creatin, or other components, which would be excreted as creatinin. Further, it is found that eyery individual has his own specific creatinin excretion, which fact again emphasizes the idea that this substance is a product of true tissue katahnl ism, having no connection with that variable metabolism, of which urea is the striking representative. These are facts which cannot be ignored. They are well established by the careful observations of Folin, and they are confirmed by a large number of observations made in our own laboratory. Turn now to that other, more conspicuous, product of proteid katabolism, urea. With a so-called average proteid intake, about 88-90 per cent of the excreted nitrogen will be in the form of urea, but, as Folin states, "with every decided diminution in the quantity of total nitrogen eliminated, there is a pronounced reduction in the per cent of that nitrogen represented by urea. When the daily total nitrogen elimination has been reduced to 3 grama or 4 gramB, about 60 per cent of it only is in the form of urea." Here, we have the chief product of exogenous metabolism, a substance quite distinct from creatinin, just as the process by which it originates is likewise quite distinct.

Exogenous metabolism is plainly a process of quite a different order from that of endogenous, or tissue metabolism. The latter involves oxidation, while the former consists hbhmi-tially of a series of hydrolytic cleavages which result in a rapid elimination of the proteid-uitrogen as urea. In this conception of exogenous katabolism, we have essentially the same viewpoint as was previously taken in attempting to explain how excess of proteid food can be so quickly decomposed, and its nitrogen removed from the body. Whether the hydrolytic cleavage is accomplished solely by trypsin and erepsin, whether it takes place only in the intestine and in the liver, or whether other glands and tissues are involved, is at present immaterial; the essential point is that we have in the body a variety of proteid katabolism, quite different from true tissue katabolism, the extent of which is dependent primarily upon the amount of proteid food consumed. The process involved is one which aims at the rapid removal of the proteid-nitrogen as urea; without incorporation of the absorbed proteid, or its decomposition products, either as an integral or adherent part of the tissue proteid. Hydrolytic cleavage is eminently fitted to accomplish this with the least expenditure of energy, while the carbonaceous residue of the proteid thus freed from nitrogen can be transformed into carbohydrate, or directly oxidized as the needs of the body demand.

As one considers these views so admirably worked out by Folin, the question naturally arises, if the real demands of the body for proteid food will not be adequately met by the quantity necessary to satisfy the true tissue metabolism? We may well believe, with Folin, that "only a small amount of proteid, namely, that necessary for the endogenous metabolism, is needed. The greater part of the proteid furnished with so-called standard diets, like Voit's, i. e., that part representing the exogenous metabolism, is not needed; or, to be more specific, its nitrogen is not needed. The organism has developed special facilities for getting rid of such excess of nitrogen, so as to get the use of the carbonaceous part of the proteid containing it." In endogenous metabolism, we have a steady, constant process quite independent of the amount of proteid food, and absolutely indispensable for the maintenance of life. So far as we know at present, its representa-l.iye cieatinin is. for a given individual the Same in amount during fasting as when a rich, meat-free, proteid diet ia_taken. The one factor that seemingly determines the amount of creatinm eliminated is the_weight of the individual, or more exactly the weight of the true tissue elements of the body, as distinct from fat or adipose tissue. Endogenous or tissue kataholism obviously calls for a certain quantity of proteid to maintain equilibrium, but this is small in amount as compared with the usual intake of proteid foods. The average man, with his ordinal; dietetic habits, consumes more nitrogen than the body can possibly make use of. The excess is not stored up, "because the actual need of nitrogen is so small that an excess is always furnished with the food, except, of course, in carefully planned experiments" (Folia).