6I :6I2.766.I

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1 6I :6I2.766.I THE INFLUENCE OF MUSCULAR WORK ON PROTEIN METABOLISM. BY H. ELLIS C. WILSON. (From the Institute of Physiology, Glasgow University.) THE problem of the relation between protein metabolism and muscular work has narrowed itself down to the question as to whether or not there is an increase in the nitrogen output as a result of work and if so what is its significance. A number of investigators found an increased nitrogen excretion after work [Parkes, 1868; Flint, 1877; Dunlop, Paton, Stockman and Maccadam, 1897; Campbell and Webster, 1922; Cathcart and Burnet, 1926]; others found no increase [Hirschfeldt, 1890; Chauveau, 1896; Atkinson, 1918]. Bornstein [1901] noted a tendency to a retention of nitrogen. It should be pointed out, however, that any increase in the nitrogen output was invariably small, and in terms of the extra protein metabolized, totally inadequate to account for the work done. Hirschfeldt [1890] and Mitchell and Kruger [1927] claimed that any increase in nitrogen excretion which did occur was due solely to an inadequate calorie intake. The balance of evidence at the moment seems to favour a slight increase. What is the significance of this increase? It is possible that apart from the increased energy turnover in the working muscle a wear and tear quota is increased. This aspect of the problem was investigated by Thomas [1910] on the human subject. He found that when, by means of a protein-free diet, the nitrogen in the urine per diem was reduced to 2-78 g., this output was increased by only 0 67 g. as a result of doing 120,000 kg. m. work. In striking contrast to this Cathcart and Burnet [1926] found that the averageincreaseinnitrogen excretion was higher the greater the nitrogen intake. The conception of an increased wear and tear associated with muscle work should be used with reserve. The wear and tear of a machine is entirely due to the frictional forces between materials which have no relation to the fuel of such a machine. In the living cell, on the other hand, structure and fuel are essentially similar materials, and as the cell contents are of a fluid nature 5-2

2 68 8H. E. C. WILSON. there is no justification for assuming anything resembling a frictional or mechanical disintegration associated with activity in the muscle cell. It must also be kept in mind that each cell unit is extremely small, where chemical and molecular forces come into play on a minute scale, and consequently if wear and tear or disintegration of tissue does exist, it must have an entirely different significance from that implied in the mechanical sense. The extensive advances that have been made in the last decade in the chemistry of muscle contraction have not until recently produced any evidence that a constituent containing nitrogen plays an active role. The discovery of creatine-phosphoric acid by Fiske and Subbarow [1929] and the fact that phosphorus appears to be closely associated with muscle activity would appear to indicate that possibly metabolites containing nitrogen may be concerned in the process of contraction. Experiments on isolated muscle cannot, however, solve the problem as to the relation of muscle activity in the intact organism to the nutritive processes as a whole. It is common knowledge that muscle tends to hypertrophy after a period of training or work. The problem which the experiments recorded here attempt to solve is the role of protein in muscle work. For this purpose the total nitrogen (Kj eldahl) and total sulphur (Denis) output (henceforth N and S) in the urine were followed. The work was carried out on the writer as subject, a male 30 years of age, weighing 65 kg. The experiments to be described were carried out with diets which differed in the form of protein they contained. The work done varied between 22,000 and 34,000 kg. m. daily, and was carried out on a hand or bicycle ergometer according to the experiment. The urine was collected for the 24 hours each day, while the work was done for a period of 1 hour. This was never exhausting and no ill effects were observed on any occasion. As in Cathc art and Burnet's observations each experiment was divided into three periods, namely: period I, before work was started; period II, the work period, which varied from 4 to 18 days in the different experiments; and period III, after the work was stopped. In Exp. 1 the basal diet consisted of the following: 100 g. cheese, 125 g. butter, 150 g. jam, 470 g. bread, one apple, total calories The work was carried out on a hand ergometer; the average amount of work done daily was 22,000 kg. m. The original object of the experiment was to determine whether the rise in N output noted by Ca thca rt and B urnet [1926], when work was carried out for a period of 6 days, would fall if the work were continued for a further period. The experiment (Table I) thus

3 WORK ON PROTEIN METABOLISM. 69 consisted of 3 days in period I, 18 days of work in period II, and 6 days after it, period III. The basal N and S outputs employed to calculate the excess of those elements excreted were taken as the average of the 3 days of period I and the last day of period III. The following are the figures employed: 8*625 g. N, 0625 g. S, S: N:: 1: 13*8. The N and S outputs tend to fluctuate irregularly above the basal values throughout the course of the experiment. In general, however, the N rises to a maximum of 1 1*368 g. on the 11th day of work and then gradually falls below the basal Exp. 1. TABLE I. 8 days' work (22,000 kg. in.) from 4th-21st day: Average for periods of 3 days each Total N Total S, A Days (g.) (g.) S:N N (g.) S (g.) S:N Period : : * : I : : : : II, : : : : II : : : : II$ : : : * : II : : : : I : : : 14*52 8* : II', : : : : III, : : IIs : 1397 Exp days' work (22,000 kg. m.) from 5th-9th day: : * : : * : * : : : : : : : : 18-70

4 70 H. E. C. WILSON. TABLE I (cont.). Exp days' work (34,000 kg. m.) from 5th-8th day: Total N Total S Days (g.) (g.) S: N 1 9*786 0*730 1: *769 1: *718 1: : : * : *796 1 : * : * : : Exp days' work (34,000 kg. m.) 7* * '791 8* * * from 5th-8th day: : : : : : : : : : : value by the 18th day of work. The 3-day averages of the N and S outputs and the S: N ratios for the 27 days of the experiment are shown in Table I. It will be noted that the N and S outputs rise to a maximum between the 7th and 12th days of work and then continue to fall to below the basal figures in the first 3 days of period III and to rise slightly on the last 3 days. The S :N ratio tends to fall from period I (1: 13-75) to 1 :15X06 in the second period of work (12) and then rises to a maximum of 1 :13x72 in the first period after work (III,). More information may, however, be obtained by calculating the excess of N and S excreted above the basal values. In the successive 3-day periods of work these are: N (g.) S (g.) S :N Period IT, :34-3,, II :45-4 J,J II :24-2,, I : 13-9,, IT :36-7,, I Retention on the first 3 days of period III, g. N, g. S, S : N:: 1 : The maximum excess is, as was to be expected, from the figures showing the total N and S outputs, in period 114. The S : N ratio of the excess rises to a maximum of 1 : 13 9 in period 114 and falls to infinity in period II6. The retention on the first 3 days after work (III,) has a S : N ratio

5 WORK ON PROTEIN METABOLISM. approaching that of muscle tissue. The sum totals of the excess N and S of the 18 days of work are 17X187 g. N and g. S, with a S: N ratio of 1: 23*4, while the total loss to the body if the retention in period III is subtracted from the excess is g. N and g. S, with a S: N ratio of 1: 24*6. The influence of work has been to cause a steadily increasing katabolism of protein, increasing to a maximum on the 11th day of work, and then falling to a figure below the basal value on the last day of work. The S: N ratio of the material metabolized is considerably lower than the basal S: N ratio of the urine or the S: N ratio of muscle tissue. From this experiment alone it is not possible to say whether it comes from food or body protein. The figures of the excess outputs, however, appear to indicate that possibly two processes are takilg place simultaneously, namely, anabolism and katabolism. It appears that when work is commenced an increased rate of metabolism, i.e. katabolism and anabolism, is initiated and that katabolism tends to exceed anabolism up to period II4. It is to be noted that the S: N ratio of the excess tends to rise to its maximum at the period of maximum katabolism. From period II4 although katabolism actually exceeds anabolism the latter appears slowly to be overtaking it and the S: N ratio of the excess output falls, indicating that the loss of S is less than that of N relatively. This may be expressed otherwise by saying that a retention of S is coming into play and would appear to favour the writer's contention [Wilson, 1925] that S is the mobile unit in both phases of metabolism. In the first 3 days after work the S: N ratio of the retained material is 1: 14-0, a figure close to that of muscle tissue. It is important, however, to visualize exactly what is taking place during the course of the experiment. The fact that at the end of the experiment the total N and S outputs are down to, or below, the basal values does not necessarily mean that the rate of katabolism has decreased from what it was in period IV. To the author it appears that under the influence of work-a katabolic phenomenon-the katabolism of protein has gradually risen, and shortly afterwards, but lagging behind it, a phase of anabolism has followed it up. The body has hence as a result of work increased its turnover of N, although the N output at the end of the experiment is the same as at the beginning. This increased turnover has, however, been effected at the cost of a loss of material, whether of body or food protein may be seen from later experiments. At this point it may be profitable to postulate what may be taking place in the active muscle. According to Cathcart [1925] two explanations are possible. On the one hand it may be that during activity the protein molecule is broken down and then resynthesized again by means of the N-free foodstuffs, 71

6 72 H. E. C. WILSON. particularly carbohydrates. On the other hand there may be an increase in the breakdown of body protein which is made up by a diversion of some of the. exogenous food protein to replace it. The observed increase might simply be an expression of the process of readjustment to the phases of resynthesis or replacement respectively. If, however, the latter assumption be true, namely, a replacement by retention, the increased excretion of N during work should be greatest on a N-free diet. Thomas' [1910] experiments, however, showed a minimal increase in N output on a N-free diet. It would then appear as if the first assumption was the more likely, namely, resynthesis, but it is possible that both processes take place. The question arises why is it that the katabolic phase was not at its maximum on the first day of work instead of 11 days later? The energy turnover was the same on the 1st day as on the 11th day of work, and it seems peculiar that the protein metabolism is not altered until much later. This delay would appear possibly to explain the role of protein in muscle work. In the first place the failure of the N output to increase on the 1st day of work seems to indicate that protein is not the source of energy for the muscles. The increased N metabolism must therefore have some indirect relationship to the increased energy exchange. Indeed it cannot be altogether surprising that an increased energy turnover in the muscles should influence the other functions of the body, such as an increased rate of N metabolism. This increased katabolism and anabolism would favour the physiological hypertrophy, not only of the muscles involved, but also of the heart, both of which ultimately show an increased functional capacity after a period of prolonged work or training. Further, the increased turnover of N would tend to show the solidarity and unity of the metabolic processes. The metabolism of each of the three foodstuffs tends to be considered separately, while in all probability the body metabolizes all three as a unit although the proportions of each metabolized in any one period of time may vary. Exp. 2 was planned in order to give information as to whether there is an increased turnover of body tissue or an increased rate of metabolism of food protein. The following diet was therefore employed in order to obtain a mixture relatively poor in S: 470 g. bread, 50 g. cheese, 100 g. butter, 40 g. gelatin, 250 g. jam, one apple, total calories The basal N and S outputs were calculated on the average of the 4 days before work (Table I), the figures obtained being g. N and g. S, with a S N ratio of 1: 17*71. The work was carried out on a hand ergometer under the same conditions as in the previous experiment and was con-

7 WORK ON PROTEIN METABOLISM. tinued for 5 days. The following are the average figures for the total outputs of N and S per diem for the three periods: N(g.) S(g.) S :N Period I (4 days) ,, II (5 days) : 17-50,, III (3 days) : 1817 It will be noted that the increase in the period of work is not considerable, and the S : N ratio has hardly altered from that of period I. In period III, however, the output of S dropped while the N output increased a little, causing a small fall in the S : N ratio from 1 : 17X55 to 1 : The excess outputs of N and S, h-owever, bring out some definite features. The excess outputs for the first 2 and the last 3 days of work and the 3 days of period III are: N (g.) S (g.) S: N First 2 days, period II : 11-3 Last 3 days, period II : 18-0 Period III 1* : 36-6 Periods II and III 4* : 2013 The S : N ratio of the excess is, as in Exp. 1, lower than that of the protein ingested as deduced from the S : N ratio of the urine in period I (1: 17.71). The S : N ratios of the various periods show, however, that the S has been excreted in advance of the N. The ratio of the excess is 1 :11x3 in the first 2 days of period II and then tends to fall to 1: 36-6 in period III. The figures would appear to indicate that the katabolic phase has risen to a maximum about the last few days of work and that from then on the anabolic phase began to creep up on it in period III, in that the excess output of S has fallen considerably. It is to be noted that the excess N output is actually greater on the 3 days of period III than on the last 3 days of period II. This is in all probability due to the usual delay in the excretion of N after S, the maximum S excretion being noted in the previous period. It is also possible that the height of the katabolic phase has not reached its maximum until period III, particularly in view of the fact that in the previous experiment the maximum N output was not reached until the 11th day of work. The fact, however, that the daily S output has begun to fall by the last 2 days of work would indicate that the anabolic phase has commenced, if it be true that S is the mobile unit in both phases of metabolism. The source of the excess material excreted may now be surmised from the results of those two experiments. In Exp. 1, with an average basal S: N ratio in the urine of 1 : 13X8, the ratio of the excess material excreted was 1: In Exp. 2, with an average basal S : N ratio in the 73

8 74 H. E. C. WILSON. urine of 1: 17-7, the ratio of the excess excreted was 1: The evidence would hence tend to indicate that the effect of work is to increase the metabolism of food protein or, expressed otherwise, to increase the turnover of the circulating protein. The S : N ratio of the excess excretion appears in both cases to be lower than that of the proteins ingested as deduced from the basal S : N ratio of the urine in each experiment. A possible and indeed probable explanation for this may be obtained from some recently published material on protein retention, where it was shown that there is a tendency to retain a material slightly poorer in S than that ingested [Wilson, 1931]. This type of retention was held to be circulating protein. If then work accelerates the metabolism of the protein in circulation, it is to be expected that the S: N ratio of the material lost will be poorer in S than that ingested. Work may then be said to increase the rate of metabolism and hence effect a loss of this material in transit. Further information on this point may, however, be obtained from the remaining experiments. Exp. 3 (Table I) was carried out on a diet containing beef, not only on account of the value attributed to beef as a food suitable for those doing physical work but also as a necessary part of a complete diet. A diet consisting of the following was ingested: 470 g. bread, 250 g. beef, 100 g. butter, 200 g. jam, one apple, total calories The work in this experiment was done on a bicycle ergometer, 34,000 kg. m. work being carried out in a period of 1 hour. It was the intention in this experiment to see if increasing the amount of work done would increase the output of N and S in the urine. The average outputs per diem in the three periods are: N(g.) S(g.) S:N Period I (4 days) : 13-77,, II (4 days) : 13-10,, III (2 days) 10* : It will be noted that the S : N ratio does not change much except for a slight rise in period II. The maximum excretion of S is, however, in period II, while the N output is practically the same in periods II and III. The excess N and S calculated for successive 2-day periods are: N(g.) S(g.) S:N First 2 days' work : 4*7 Second 2 days' work : days after work : Total for periods II and III : 6-7 The S : N ratio of the total excess is remarkably high but, as in the previous experiment, the major part of the S has been eliminated early as is seen from the high ratio in the first 2 days' work period. It would appear

9 WORK ON PROTEIN METABOLISM. that in this experiment the anabolic phase has not commenced as in the previous ones. This is possibly due to the increased amount of work carried out daily or to there being only 4 days of work. The strikingly high ratios of the excesses in this experiment in contrast to the previous ones merit some attention. In Cathcart and Burnet's experiments [1926] the S : N ratio of the excess outputs was, in all but one, about The exception in their case was with the beef diet, where the ratio of the excess outputs was 1: 14*8-approximately twice as high as in their other experiments. Those workers also noted that the excess outputs of N and S were greater in period III than in the period of work, while our figures show the excess N output on the 2 days after to be very little lower than on the last 2 days of work. No explanation can be offered for this peculiarity in regard to the influence of a beef diet except to point out that it is evidently no casual phenomenon, as our figures for the S: N ratio of the excess outputs on the beef diet as compared to the other diets show the same trend as those of C athcart and Burnet although the absolute ratios are higher. Exp. 4 (Table I) was carried out on a diet containing eggs in order to have a relatively high intake of S. The diet was: 470 g. bread, 125 g. butter, 4 eggs, 200 g. jam, one apple, total calories The same amount of work (34,000 kg. m.) as in the previous experiment was done on the bicycle ergometer. The experiment was divided into three periods, the basal outputs of N and S being based on the average of the last 2 days of period I. The figures giving the average outputs of each period are: N(g.) S (g.) S: N Period I (2 days) : II (4 days) : III : It will be noted that as the diet was relatively rich in S, the S : N ratio was throughout high; further, work has had no influence on the output of N except in period III, when a retention has taken place. The S alone has risen in period II only to fall almost to its basal value in period III. The following figures show the balance: First 2 days' work g. N excess g. S excess Second 2 days' work g. N retained g. S excess 3 days after work g. N retained g. S excess Total N retention g. Total S loss g. It will be noted that S alone is lost, while the N shows a positive balance. It is to be observed further that the loss of S is mainly on the first 2 days of period II, while the retention of N is almost entirely in 75

10 76 H. E. C. WILSON. period III. This would again tend to confirm the theory that S plays the mobile role in the katabolic phase. The question, however, as to why there is no loss of N is rather difficult to explain. It may be that the excess excretion of N is masked by a greater retention, indicating that the anabolic phase has actually overtaken the katabolic in period III. If this is so, however, the fact that there is no retention of S may suggest itself. Several possibilities can be offered in explanation of this peculiarity. In the first place previous experiments [Wilson, 1925] show that the body stores the N of egg albumen to a considerable degree (70 p.c.) while the S is rejected. If then in this experiment there is a tendency to retention it is possible that the N alone is retained. On the other hand it is possible that, as the S: N ratio of the basal diet is high, as judged by the ratio in the urine of period I, the material in transit is relatively rich in S. In the experiments quoted [Wilson, 1925], although the S of the egg albumen was rejected, it was metabolized very slowly, the maximum excretion being on the day following the superimposition. Under these circumstances as the egg diet was being consumed daily it is extremely likely that the material in transit was rich in S. If then there is a tendency for the body to consolidate some of this material into a substance resembling muscle tissue, S would be eliminated and N retained. The previous experiments with the exception of number 3 (beef diet) would tend to confirm this. In Exp. 1 with bread and cheese the S: N ratio of the urine in the period before work was 1: 13 7, and in all probability the S: N ratio of the material in transit was lower [Wilson, 1931]. If then there is a tendency to stimulate the katabolism of this material in transit (circulating protein) the S: N ratio of the excess would be low, in Exp. 1 for instance ; if also there is a tendency to consolidate some of this circulating protein into muscle tissue one would expect the N to be rejected more than the S. Exp. 2 with a S: N ratio in period I of 1: had an excess output with a ratio of 1 20*13. In Exp. 4 on the other hand the basal S: N ratio of the urine in period I was 1: 11-83, and correspondingly if there is a consolidation of some of the material in transit, a greater output of S than N is to be expected. Briefly if muscle work tends to promote the katabolism of protein, and if further the material built up in the later phase is tissue protein with a S: N ratio of 1 : 140 approximately, it is to be expected that the excess excreted will have a ratio lower than 1: 14*0, if the S: N ratio of the food is lower than this, while if the S: N ratio of the food is higher than 1 :14 0 the excess excreted will have a higher ratio. The process may be compared to a discarding of certain moieties of the circulating protein in order that its

11 WORK ON PROTEIN METABOLISM. composition may approximate to that of tissue protein. It is here possibly that Rubner's [1911] conception of a transitional protein (tbergangseiweiss), intermediate in stability between circulating and organized protein, may be justified. Muscle work may initiate a process of transformation of circulating protein into transitional protein with a discarding of the unnecessary elements. That the endogenous turnover is increased appears unlikely in view of the figures here tabulated for comparison from the four experiments, showing on the left the S : N ratio in the urine in period I in each case, and on the right the S: N ratio in the excess outputs: Exp. 1 1: : : : : : : The results with the exception of Exp. 3 would tend to show that the increased metabolism of protein is concerned primarily with the food protein, and no indication is given that the endogenous metabolism of body tissue is increased. Two questions yet remain to be answered however: (a) Is the excess N and S output in any way related to the level of protein intake? (b) Is the excess output related to the amount of work done? Comparison of the average daily excess N and S outputs for the first 4 days of each experiment with the basal outputs of N and S gives these results: Basal output Excess output. Average for first 4 days' work N (g.) S (g.) N (g.) S(g.) Exp * Cathcart and Burnet [1926] in general found that the higher the protein intake the greater the excess of N in the urine. As the intake in their diets varied from 8 g. to 17 g. per diem it would seem that one of the factors concerned in the amount of the excess excreted is the level of the protein intake. In the experiments recorded here the N intakes did not vary much, but it would appear that not only the amount of protein ingested but also its quality may play a part. In Exp. 2 for instance on a bread and gelatin diet the average excess outputs per diem for the first 4 days is g. N and g. S, while in Exp. 4 with bread and eggs there is no excess excretion of N, the excess of S amounts to 0*043 g. Further, the amount of work done per diem in Exp. 2 was 22,000 kg. m. as opposed to 34,000 kg. m. in Exp. 4. In previous experiments [Wils o n, 1925] 77

12 78 H. E. C. WILSON. it was shown that the retentions of the N of gelatin and egg albumen were 50 p.c. and 70 p.c. respectively, while the S of both proteins was rejected. The egg albumen appeared to be more resistant to metabolism than the gelatin, in that 5 days elapsed before the outputs of N and S approached the basal figures. It seems probable then that not only the level of protein intake but also its quality may determine the amount of increase in the excretion of N and S under the influence of muscle work. In order to find out if there is any correlation between the amount of work done and the excess excretion of N, the total excess output for each experiment, including the period after work, has been divided by the total amount of work done and the results expressed as increased N output per 1000 kg. m. work. The following figures are obtained: mg./1000 kg. m. Exp. 1 (bread and cheese) 43 VP 2 (bread and gelatin) 37,, 3 (bread and beef) 15,, 4 (bread and egg) Nil These figures do not appear to indicate that the absolute increase in the output of N is a constant charge per unit of work and quite independent of the nature of the protein ingested. The foregoing experiments would then permit the following tentative conclusions to be drawn. An increase in the excretion of N is evidently not associated directly or necessarily with the energy requirements of the working muscles. Mitchell and Kruger [1927] maintained that the slight increase observed was due to an insufficient caloric intake or perhaps even to a temporary local starvation of the cells. This idea is a priori unlikely, as the influence, on this assumption, should be observed early in the course of the experiment, while as has been noted in Exp. 1 the maximum output of N was on the 11th day of work. It may then be concluded that the influence of work is to increase the rate of katabolism and the processes of resynthesis of protein in the cells. The question arises as to whether it is an increase of the endogenous metabolism of the tissues or of the exogenous metabolism of the food protein. If the endogenous metabolism were increased one would expect the excess outputs of N and S and the S : N ratio to be the same in each experiment, regardless of the quantity or quality of the protein ingested. This, however, is contrary to the observations noted here and those obtained by Cathcart and Burnet [1926] and Thomas [1910]. The latter found an insignificant increase of N in the urine after doing actually 105,000 kg. m. work for 3 days on a N-free diet. Other workers [Dunlop, Paton, Stockman and Maccadam,

13 WORK ON PROTEIN METABOLISM. 1897] noted a rise in the excretion of uric acid in untrained subjects after work, while Cathcart and Burnet [1926] found insignificant increases in the creatinine excretion, which they attributed to the protein of the diet rather than to the work itself. The only other possibility is then that the increase in the excretion of N and S is due to an increased rate of metabolism of the food protein ingested. The figures for the excess excretion of N and S and the S: N ratio, along with the corresponding figures for the basal outputs, would appear to indicate that the rate of turnover of circulating protein is increased. Evidence has also been adduced which tends to show that probably the katabolic phase is first stimulated and is later caught up by an equal or greater increase in anabolism. It also seems likely that the quality of the protein ingested determines in some degree the rate at which its katabolism is accelerated and possibly also its capacity for taking part in the anabolic phase. The evidence obtained from the experiments with gelatin and egg albumen respectively favours the viewthat there is a consolidating of the circulating protein into a material which approaches in its S: N ratio to that of body tissue. Taken all over it appears that the metabolic processes of the body should be considered as a whole. The organism does not appear to metabolize protein, fat and carbohydrate, each of them entirely independently of the other two. Rather it would seem that if the energy turnover is increased, the turnover of nitrogenous matter tends also to increase, and similarly when the turnover of nitrogenous matter is increased by means of additional dietary protein, a rise in the energy output follows, as is illustrated by the specific dynamic action of protein or indeed of any of the energy yielding foods. What the significance of this increase in nitrogenous metabolism during work may be is not certain, but it is possible that it is of advantage to the organism, particularly in relation to the muscular hypertrophy and improved physical well-being that ultimately follows prolonged training. SUMMARY. 1. The influence of muscle work on the human subject is shown under certain conditions to cause an increase followed by a decrease in the excretion of N and S in the urine. 2. The increase in the excretion of N and S is shown to have no relation to the amount of work done. It appears that the quality of the protein ingested is one of the factors which influences the amount and the S: N ratio of those elements excreted above the basal value in the urine. 79

14 80 H. E. C. WILSON. 3. Evidence is adduced which tends to show that the rise in the excretion of N and S is not caused by an increase in the endogenous metabolism, but is possibly due to an acceleration in the metabolism of food protein. 4. The results have been interpreted as showing that muscle work causes an increase in the katabolism of protein which is later followed by a compensatory anabolic phase. 5. The material retained in the anabolic phase tends to approximate in its composition to body tissue as judged by its S: N ratio. I desire to acknowledge my indebtedness to Prof. Cathcart for much helpful advice and criticism during the progress of this work. Part of the expenses of this research was defrayed by a grant from the Andrews Fund, for which I express my thanks. REFERENCES. Atkinson, H. V. (1918). J. Biol. Chem. 33, 379. Bornstein, K. (1901). Pflueger8 Arch. 83, 540. Campbell, J. A. and Webster, J. A. (1922). Biochem. J. 16, 106. Cathcart, E. P. (1925). Phy8iol. Rev. p Cathcart, E. P. and Burnet, W. M. (1926). Proc. Roy. Soc. B, 99, 405. Chauveau, A. (1896). Acad. Sci. Paris, 122, 504. Dunlop, J., Paton, D. N., Stockman, R. and Maccadam, I. (1897). J. Physiol. 22, 68 Fiske, C. and Subbarow, Y. (1929). J. Biol. Chem. 81, 629. Flint, A. (1877). J. Anat. London, 11, 109. Hirschfeldt, F. (1890). Virchow8 Arch. 121, 301. Liebig, J. (1846). Tierchemie. Braunschweig. Mitchell, H. H. and Kruger, H. K. (1927). J. Biol. Chem. 76, 55. Parkes, E. A. (1868). Proc. Roy. Soc. 16, 44. Rubner, M. (1911). Arch. Anat. Physiol. (Physiol. Abt.), p. 69. Thomas, C. (1910). Ibid. p Voit, C. (1881). Hermanns Handbuch der Physiologie. Leipzig. Wilson, H. E. C. (1925). Biochem. J. 19, 322. Wilson, H. E. C. (1931). J. Physiol. 72, 327.