FACTORS IN ENDOGENOUS URIC ACID METABOLISM RALPH CONNER CORLEY A. B. University of Illinois, 1921 THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF ARTS IN CHEMISTRY IN THE GRADUATE SCHOOL OF THE UNIVERSITY OF ILLINOIS, 1922 URBANA, ILLINOIS . . UNIVERSITY OF ILLINOIS THE GRADUATE SCHOOL May 24 1 HEREBY RECOMMEND THAT THE THESIS PREPARED UNDER MY SUPERVISION BY RALPH ■ CO LLEY. ENTITLED. ACIQRS-I3L ENDO GEIJOUS BE ACCEPTED AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE DEGREE OF Master of Arts in Ch^istry U/'i Jl, ATfr-j ^k*er> In Charge of Thesis Head of Department Recommendation concurred in'* Committee on Final Examination* •Required for doctor’s degree but not for master’s S9i ' Digitized by the Internet Archive in 2015 https://archive.org/details/factorsinendogenOOcorl TABLE 0 S CONTENTS I INTRODUCTION • II HISTORICAL ................ Ill EXPERIMENTAL * ......... A. Methods ............... E. Controls. .............. C. Effect of Glyeocoll D. Influence of Eat. . . . E. Fat and Gly cocoll . F. Glycerol G. Honey. ...... H. Karo Corn Syrup ........... I. Cystine. . IV GENERAL DISCUSSION OF RESULTS, ...... V SUMMARY ' VI BIBLIOGRAPHY . . 1 2 7 7 8 8 9 10 10 11 12 13 14 57 28 I wish to express rny sincere gratitude and appreciation to Dr. Howard 3. Lewis for his constant assistance and inspiration dur- ing the course of these experiments. I INTRODUCTION The question of general metabolism is intimately bound up with the question of endogenous uric acid metabolism* This is a logical corollary of the facts that tissue metabolism is in- herently cellular, and cellular activity has as one important factor nuclear metabolism. Furthermore in the final analysis, the elimination of endogenous uric acid is an index of the breakdown of nuclear material. With these facts in mind, it is apparent that advances in the theory of nuclear metabolism must of a necessity afford a firmer foundation for the development of our theories of general metabolism. It is therefore deemed advisable to consider all aspects of this general problem. The relation of protein and protein derivatives in the diet on en- dogenous uric acid excretion has been rather thoroughly inves- tigated. The purpose of the present paper is to report inves- tigations in regard to the effect of other types of food-stuffs, particularly fats and carbohydrates upon endogenous uric acid metabolism II HISTORICAL Uric acid has been a well recognized constituent of the urine for nearly a century and a half since Scheele(l) isolated it from urine and urinary calculi. Some hundred years later, the correlation of gout with uric acid was established by Pearson(2 ), It remained, however, for Kossel (3) to lay the foundation stores of present uric acid theories by demonstrat- ing the relation of uric acid, and other purines to nuclear metabolism. Burian and Schur(4) were the first to clearly distinguish the two kinds of urinary uric acid as differentiated by origin- exogenous, that derived directly from preformed purine precursors in the diet and endogenous, that resulting from the vital pro- cesses of the cell. Thus according to the definitions now ac- acid cepted exogenous uric acid is that fraction of the uric /of the not 1 urine which has/ been a part of the living cells or tissues of the organism, while the endogenous factor is a product of the activity of the cell and has been formed from an actual consti- tuent of the protoplasm. Burian and Schur concluded that the endogenous portion of the uric acid eliminated was constant and independent of the diet. Burian believed that endogenous uric acid was formed principally from the hypoxan.thine of inosinic ae i i , one oi the mononucleotides found only in muscle tissue. In accord with this theory he believed that muscular work would increase trie endogenous uric acid. Siven(5) repeated various - 3 - acid phases of Burian*s work, and while he found that the uric/ elimi- nation was greater during working than sleeping hours, in general he failed to confirm the view of Burian that muscular work in- creased the uric acid output. On the other hand, Mares(6) was of the opinion that some or possibly all of this excreted uric acid resulted from glandular activity, particularly that of the digestive glands. In support of his idea, he showed that the ingestion of food free from pre- formed purines caused a marked increase in the amount of uric acid eliminated. He argued therefore that the observed increase resulted from the disintegration of nuclear material in the glands of the alimentary tract, as a result of the work imposed on them during the process of digestion. Smetanka( 7 ) confirmed Mares results, but was forced to make an extension of Mares theory since he found that honey, a food requiring very little digestion since it is essentially invert sugar, a mixture of the two mono-saccharides, glucose and fruc- tose, also increases the uric acid excretion. He interpreted his results to indicate that uric acid was formed as a result of trie increased breakdown of nuclear material during the period of the exaggerated glycogenetic activity of the liver. Mendel and Stehle(8) came to the conclusion that a part at least of the endogenous uric acid originated from the activity of the alimentary canal. The striking part of their experiment was that pilocarpine a drug stimulating glandular secretion in- creased the excretion of uric acid, while atropine an inhibitor \ l . .. - X * / - -4- of glandular activity caused a decrease in the output of uric acid. However, they found that the mechanical work of the di- gestive tract caused by the administrat ion of bulky food or lax- atives was not a factor in the stimulation of uric acid output. Considerable work has been done on this problem and various theories have been advanced to explain the observed phenomena. The simplest way to get a view of the entire problem and the ad- vances that have been made, is probably to give a brief recapi- tulation 14) of the most important theories which have been sug- gested from time to time. Thus the increase of uric acid elimi- nation following the ingestion of purine free foods have been attributed in general to the following factors, (a) Nuclear disintegration in the glands of the alimentary canal occasioned by the work of digestion( 6 ), ( 7 ), ( 8 ). (b) Nuclear disintegration associated with the work of digestion and food storage(7). (c) Synthesis of purines from carbohydrates^ 9 ). (d) Synthesis of purines from arginine and histidine( 10 ), ( 11 ). (e) Stimulation of the process of elimination which was suggested by Lewis, Dunn and Doisy (12), but regarded by them as untenable, (f) General stimulation of cellular metabolism by amino acids or their cata- bolic derivative( 12 ). The objection to the theories of Mares and Sme tanka is that it is scarcely conceivable that nuclear disintegration of the tissues of the digestive apparatus or liver would be sufficient- ly extensive to account for the relatively large increases in uric acid elimination. It is of course quite conceivable that a part at least of the uric acid has this origin but such/theory _c, _ does not account at all for the marked effect of amino-acids, which probably do not affect to any marked extent the digestive apparatus in the process of their digestion. The chief advocates of the formation of purines from carbo- hydrates are Graham and Poulton(9). As one support of their theory they point to the conclusions of Enoop and V/indaus( 13 ) who found that when glucose is exposed to the action of sunlight and the highly dissociated compound Zn( OH )a .4NH3, methyl glyoxal and 9-methyl imidazol are formed. Notwithstanding these interest- ing experiments conducted invitro it scarcely seems probable that carbohydrates are concerned with the synthesis of uric acid or other purines. Ackeroyd and Hopkins(lO) found a decrease in allant 0 in ex “ cretion when young rats were fed diets free of arginine and his- tidine. Harding and Young(ll) came to similar conclusions when they observed that the feeding of placenta, which has a high content of arginine causes more of an increase in allantoin ex- cretion than does an equal amount of muscle tissue. On the con- trary, other authors( 19 ) have been unable to show any relation- ship between the arginine and histidine contant of the diet and the uric acid or allantoin output of the urine. While the data in regard to the relation suggested between uric acid and arginine and histidine seem at first thought quite contradictory, as Rose(14) points out in a recent paper, it is possible to consider these mutually supplementory , the differences being due to quantitative considerations in the living body. - 6 - Further work oil this subject will be quite valuable, if it can clear up the problem or at any rate point to a means for its solution. The most recent theory and seemingly the most adequate is that presented by Lewis, Dunn and Doisy(12)» According to this conception increases in uric acid elimination following inges- tion of purinee-free protein or amino-acids are due to a general cellular stimulation, caused by the amino-acids or some of their catabolic derivatives. Following quite different methods and experimental techni- que, Hose was led to the same conclusion as that expressed by Lewis and collaborators. He, however, extended the theory and decided that the increases following ingestion of other food- stuffs or chemical substances is due xo a general stimulating action upon cellular metabolism caused by digestive or metabol- ic products of such foods or chemical substances.. In order to put this theory on a firmer basis and to see whether it is generally applicable it was deemed advisable to extend the work of Lewis and collaborators to the other types of food stuffs, fats and carbohydrates and to their cleavage products as far as possible. This phase of the work has formed the subject of the present invest igat ion. III EXPERIMENTAL Methods Uric acid was determined colorimetrieally by the Benedict and Hitchcock modification of the Eolin-Macfcllum **DenA$ method. Creatinine was determined by Polin' s colorimetric method. The subject of these experiments was a healthy young mail, aged 21 years, with a weight of about 67 kilos. The experiments were usually conducted on Wednesday 7, and Eriday. Prom Monday even- ing until the conclusion of the experiment Eriday, a diet practi- cally free of purines and low in protein was consumed. During the experimental days no food was eaten after 6 : 00 P.M. the pre- ceding day, at which time a light meal only was consumed, until the completion of the experiment or experiments. Later in the course of the experiments, two were run on succeeding days usually Tuesday and Wednesday, the same general dietary regulations being observed. As in other similar experiments conducted in this labora- tory(15) 200 ec. of water were ingested hourly, to insure that the volumes of the urine collected be large enough to minimize erros due to manipulation or incomplete emptying of the bladder* Since the excretion of creatinine tends to remain constant from hout to hour, and is not influenced by the diet, if creatinine free, this constituent of the urine was also determined to give an index of the completeness of the collection of urine. - 8 - Controls In order to interpret the significance of changes in uric acid excretion following ingestion of various food— stuffs and other substances, it is necessary to have accurate information concerning the degree and kind of variations to be expected in the fasting subject normally. Control experiments, in which no food at all was eaten during the course of the experiments, were carried out and repeated at frequent intervals, in order to de- termine whether or not the level of endogenous uric acid metabolr* ism was altered by such experiments as these. As has already been observed by Mendel and Stehle(8) and Heuwirth ( 15 ) and others in this laboratory, there is a tendency for the uric acid elimination to decrease steadily during the day. The hourly variations observed were much less marked than some other investigators have reported( 14 ), (15). Since under the control conditions the elimination of uric acid is subject to a stead}?- decrease, the assumption seems warranted that aiiy marked rise in the level of excretion, particularly during the later morning hours, is caused by the substances ingested. Effect of Glycocoll It has already been shown in this laboratory that the inges- tion of amino acids causes a marked rise in the endogenous uric acid excretion. In order, therefore, to get a comparison of the relative increases caused by amino acids and the other food stuffs to be studied, it was considered advisable to repeat the experi- ments with glycocol (Table II). This experiment served also to -9- determine whether the reaction of this subject to amino acids was similar to that which has been observed in other individu- als^ ). It will be noted from the table that there is a quite apparent rise the first hour following administrat ion, with the maximum effect the second and third hours* The effect has scarcely disappeared by the fifth hour, when the experiment con- c luded.. Influence of Pat. Practicall3 r all the available work done on the effect of fat on the uric acid excretion seems subject to the objection t nan that it has been conducted on a daily rather /on an hour ly basis, and furthermore that other food-stuffs have been present in the diets studied. Hermann (16) and Horbaczewski and Kenera( 17 ) reported a di- minished uric acid excretion following the consumption of butter (100 g daily). Umeda( 18 ) likewise found that the uric acid ex- cretion was diminished on a fat-rich carbohydrate-poor diet. Mendel and Stehle in a study of hourly elimination found that the eating of butter caused no apparent change in the uric acid excretion. Table III presents the results obtained with butter and cream. Neither cause any apparent change in uric acid output which was quite similar to that obtained during the fasting con- trols. Since it is well known that fat is relatively slow ly di- gested and absorbed, it seemed advisable to continue the experi- ments for a larger period of time in order to afford time for . - i ^ ^ i - - 10 - the fat to be digested and absorbed, so that it might exert any possible metabolic influence. For this reason experiment 14 was run six hours, and experiment 25 was run seven hours after drinking the cream* During this time which seems extend- ed enough for the complete absorption of the fat no effect on the uric acid elimination was detected. Fat Followed by Glycocoll Ingestion. In view of the experiments just considered (Table IV) it was deemed interesting to determine whether the previous feed- ing of fat would in any w^ay interfere with the stimulating ac- tion of amiiio-acids on the uric acid excretion. For this pur- pose the consumption of cream was followed by the ingestion of glycoccl (10 g) three hours later. In confirmation of other experiments there was at first a steady fall in the uric acid output. However, under the influence of the glycocol there was a marked increase in the uric acid elimination, the second hour after. It is of course noted that at this time of day the general level of excretion is already lower so that the absolute rise is not so marked as in the experiment conducted earlier in the day. The relative increase is however quite marked. Glycerol Horbaczewski and Kanera(17) and Umeda( 18 ) found that the ingestion of glycerol caused a noticeable increase in uric acid elimination* These writers noted that while free glycerol caused an increase, glycerol combined in the fat molecule - 11 - caused no such effect. Results in accord with those of earlier workers are re- corded (Table V). The ingestion of 5° S °f glycerol caused in each case a marked rise in uric acid output. 10 g had no ap- parent effect ♦ Influence of Honey Smetanka found that the ingestion of honey (200 g) caused an increase in uric acid excretion. It was on the strength of these results that he advanced his theory that the disintegra- tion of not only the cells of the digestive tract, cut also of the liver during glycogenetic activity was responsible for the observed increases in uric acid elimination. He came to this conclusion since the digestion of honey imposes very little work on the alimentary canal. In connection with Smetanka* s work concerning the effect of honey, the investigations of Graham and Poulton and of Umeda are of interest. These authors believe that a part of the endogenous uric acid may arise through synthesis from carbo- hydrates. The observation of Knoop and Windaus in regard to invitro synthesis of purines has already been cited. In Table VI are given the results of 7 exp erimeiits in re- gard to the effect of honey. All of the experiments show' a marked rise in the excretion of uric acid. The hourly samples of urine were tested for sugar, using Benedict’s solution. There was no apparent correlation, however between glycosuria and uric acid level, since at times the test was positive and - 12 - in another similar experiment the test would be negative. Thus one sample of urine contained sugar when 110 g of honey was taken while in several experiments there was no glycosuria fol- lowing the ingestion of 200 g of honey. Effect of Karo Corn Syrup. As has already been alluded to carbohydrates ri-ch diets seem to cause an increase in endogenous uric acid. In Table VII are given the results of experiments in regard to the effect of Karo cane-syrup on the uric acid excretion. It will be seen that in general the ingestion of smaller amounts than 200 g show no efiect, those above 200 g consistently show an increase in txie uric acid elimination while those in the neighborhood of 200 g show some positive and some negative results* The conclusion seems inevitable therefore that there is a quantitative relationship between the amount of glucose ingested and tne effect produced. For the subject of these experiments it seems that 2 00 g my be taken as the critical point. If less than thls amount was taken there was no effect, while more than this amount gives a decided effect. oince honey is essentially invert sugar and cose and fructose, /the the sugar of the Karo , . , , . 1 /is glucose dicat ed oy analysis /it w r ould be interesting effect fructose alone would have. The cost , a mixture of glu- corn s3/rup, as in- to determine what of the pure fructos e prevented such experiments being conducted. 1 . Analysis of Corn Syrup. Sherman’s food Products, Hew 'fork -ater 19.0 per cent Dextrine 42.0 per cent Glucose 38. 5 per cent Ash 0.5 per cent I - 13 - Cystine Table VIII gives the results of one experiment involving the ingestion of 5 g of cystine. The difficulty of taking the cystine into solution prevented a repetition of this experiment. A solution acid enough to hold the cystine in solution was too strongly acidic to be swallowed. Several attempts to do so pro- duced a mild nausea. 3 g gave little effect and yet it seems that there is an actual ris,e in the uric acid excretion. — 14 — IV GENERAL DISCUSSION OF RESULTS It has been well established that the endogenous uric acid excreted is not independent of the diet, and furthermore that purine free proteins cause a marked use in the excretion oi uric acid. More recent work, particularly from this laboratory,] has shown that amino acids have the same marked effect as pro- teins themselves. These reults have been interpreted as indi- cating that the increase in uric acid elimination is due to a general stimulation of cellular or nuclear catabolism, by the amino acids or some of their catabolic products. It, however, has been observed frequently that proteins and protein derivatives are not unique in their stimulation of uric acid metabolism, but that various other types of substances] give rise to the same phenomena. The results presented in this paper are quite in accord with most other work that has been done on this subject. Vari- ous invest igators to be sure have found that a fat -rich carbo- hydrate poor diet causes a decrease, while the results present- ed in the present paper indicate that the ingestion of fat causes no apparent effect oxi the uric acid excretion, however, these results are not entirely contradictory for the work was carried out under slightly different conditions, inasmuch as in the experiments cited, the effect of the fat alone was not de- termined and the results are merely the effect of the fat in conjunction with other types of foodstuffs. - 15 - At first thought it seems peculiar that free glycerol causes a marked effect while glycerol combined in the fat mole- cule seems to exert little influence. However, much less glycer- ol was ingested in the form of fat than when it was ingested alone. Besides it is necessary to consider the time relations that obtain. Glycerol is quite soluble so that it should be absorbed immediately while it is well known that the digestion of fat proceeds at a comparatively slow rate with a consequently slow liberation of glycerol. In general it seems as if the effect produced by these var- ious non-protein foodstuffs is dependent on the rate of absorp- tion. That is to say the more rapidly the substances enter the system from the alimentary tract, the greater the effect they would be likely to produce, assuming that their action obeys the Mass Law for the effect of concentration of one constituent upon the speed of a given reaction. In accord with this view it must oe borne in mind that the corn syrup fed contained con- siderable dextrin which would probably require some further di- gestion, while honey being formed chiefly of monosaccharides would De immediately absorbed. Tne objection of course may be raised that there is scarce- ly enough difference in digestion periods of these various types of foodstuffs, to account for the difference in effect. However, very slight differences in time are all that are required to explain the observed differences in uric acid excretion. It is oi importance to notice the quantitative relations that have been brought out in this study. Host foodstuffs exert -16- some specific dynamic action, proteins and amino-acids being by far the most pronounced in their influence, while fats and carbo- hydrates have much less effect. Similarly 10 g of amino-acids caused a marked increase in uric acid excretion, 200 g or more of carbohyd rates a somewhat weakened effect, while 200 g of fat had no noticeable action at all. The objection exists, it must be admitted, that fats which do not affect uric acidelimination have more of a specific dynamic action than carbohydrates, which have beeti shown to cause a rise in uric acid excretion. It is deemed interesting and probably of some significance however to call attention to the rough correlation existing between specific dynamic action and influence on endogenous metabolism. Further— more it is to be particularly noted that the types of foodstuffs other than proteins and protein derivatives exert an influence on the uric acid elimination only when very large quantities are consumed, that is when the organism is essentially overwhelmed bj r the absorbed substances* It would seem therefore as a result of the work presented in this paper, and from previous work done in this laboratory and elsewhere that is quite probable that one of the factors, at least > in the rise of uric acid excretion following the ingestion of various purine-free foodstuffs, is due to a general stimula- ting action upon cellular metabolism and consequently upon nu- clear catabolism, of digestive or catabolic products of the in- gested substances. . I .. 1 . > 1 1 .. -17- table i Normal Controls No Food Ingested it Experiment 1 Experiment 3 Hour Vol U.A. Kr Vol U.A. iCr 7-8 70 32.0 56.5 310 27.8 62,7 8-9 400 33.8 77*5 660 32.7 73*7 9-10 290 29.7 70.0 310 32.3 71.7 10-11 150 29.6 61.5 160 24.9 56.5 11-12 210 28.6 76.5 120 27.0 76.4 it it Experiment 9 Experiment, 15 Hour Vol U.A. Kr Vol U.A. Kr 7-8 230 31*4 64.8 160 31.2 60.6 8-9 400 33-4 68.7 400 34.3 69 »2 9-10 263 32.9 68.2 285 31.6 62.8 10-11 100 31.0 64.2 250 27.3 65 »6 11-12 30 26.9 68*2 70 24.6 64.8 * Experiment 20 Experiment 31 Hour Vol U.A. Kr Vol U.A. Kr ► 7-8 305 28.8 66.6 70 22.7 66 .8 8-9 325 28.7 - 62.8 325 22.0 69*2 9-10 265 28*9 66.2 233 24,1 70.5 10-11 70 26.6 62.6 210 22.5 69.2 11-12 70 22.2 66.5 290 23.4 65.0 ^Exp % 1, 0$t. -.4 1921: Exp. 2i; 1921: Oct. 26 r»c. 7, , 1921: 1 1921: EXP. Jan. 11 .2f Mar » l > ..'I -18- TABLE II Influence of Glycocoll 10 g of glycocollat 9 o’clock it Experiment V Hour Vol U.A. Kr 7-8 45 23.0 63.O 8-9 260 28.8 69*3 9-10 95 45.0 67*4 10-11 360 48 *2 68.2 11-12 175 33*6 66.8 12-1 80 28.6 65*5 * October 28, 1921 -19- TAELE III Influence of Eats Experiment 4 Experiment 6 Hour Vol U. A. Kr Vol U.A. Kr 7-8 250 36.2 60.8 275 35*7 6I.3 8-9 429 34.5 42.5 350 35.5 65*8 9-10 295 49.2 770 60 33-7 68.7 10-11 170 29*8 54*5 225 28.6 64.4 11-12 90 33*5 62.5 265 28.6 66.2 12-1 1?0 26.8 62.3 220 28.5 68.2 it Experiment 14 * Experiment 25 Hour Vol U, A. Kr Vol U.A. Kr 6-7 249 32.8 72.3 93 26.9 76.3 7-8 595 350 65.2 63 18.5 67.5 8-9 100 35 • 0 75.0 96 24.0 82.0 9-10 260 36.1 71.3 60 26.4 62.3 10-11 88 24.9 65.4 62 19.8 75.5 11-12 149 23.8 64.2 88 20.1 69.8 12-1 90 270 69*2 165 18.3 66 .2 1-2 - - - 61 19.1 75 * 0 ^Exp. 4, 100 g of butter at 9 o’clock, Oct. 26, 1921 6, 1/2 pt. of whipping cream at 8 o'clock, Kov. 2, 1921 14, 1 pt . " " " 11 7 " Dec., 2, 1921 29, 1 « " " " " 7 M Jan., 29, 1922 .. -■ . -2 CI- TABLE IV Influence of GlycocollFollowing Pat Ingestion.. * Exp er intent 28 Hour Vol U.A. Kr 7-8 63 24.2 68.4 8-9 210 23 V 7 68.2 9-10 205 22.5 65*0 10-11 130 23.1 66.8 11-12 77 26.4 66 . 8 12-1 255 30.1 70.0 1-2 73 23.8 65*2 2-3 60 20.0 63*8 1 pt. of cream at 8 o’clock and 10 g of glyeo cdl at 11 o’cloc i L.-, • 21 - TABLE V Influence of Glycerol it it Experiment 26 Experiment 27 Hour Vol U.A. Hr Vol U.A. Kr 7-8 390 33*9 66,7 95 21.6 56*8 8-9 155 29.9 5 O .5 160 35*3 55*0 9-10 93 41.5 59*4 77 39.6 52.7 10-11 80 37*1 55*5 28 25.6 53*7 11-12 190 29*9 58.9 135 27.2 58.2 12-1 195 22.1 u . Experiment 3° 61.2 330 21.2 Experiment 54.3 it 32 Hour Vol U.A. Kr Vol U.A. Kr 7-8 72 26.7 65.5 135 21.2 67*5 8-9 255 29*5 63*8 140 21.2 65-7 9-10 100 39.6 60.7 82 31*5 65*2 10-11 72 30.0 60.0 73 34.2 69.3 11-12 250 25*9 60.6 60 25.8 66.7 12-1 225 Exper 23.1 it iment 33 65 *4 320 22.2 65.9 Hour Vol U.A. Kr 7-8 290 23*9 65.9 8-9 32 0 28.9 67.5 9-10 74 24.1 58.7 10-11 220 23.6 67.2 11-12 235 22.1 60.2 12-1 55 *Exp. 26 50 £ 2? 50 § 36 50 g 22.3 gl3rcerol 8 U j •< 8 58.5 0 * clock w 11 I^Ii 2/28/22 : Exp. 32 . Exp. 33 55 0 • 10 0 ' g glycerol clock 3/7/22 g glycerol clock 5/8/22 I I ,1 Kour 7- 8 8- 9 9- 10 10-11 11-12 12-1 Hour 7- 8 8- 9 9- io 10-11 11-12 12-1 *Exp - 22 - TABLE VI Influence Experiment 7 Vol U.A. Kr 145 31.2 57*2 205 29.3 68.8 80 34.3 62.7 92 32.1 69.7 450 35.5 66.5 150 31.8 59*1 it Experiment 19 Vol U.A. Kr 125 34.1 64 • 8 155 25.8 61.7 110 29.8 62 » 0 295 36.9 65*3 32 0 33*5 64.0 185 28.9 62.2 f Honey Experiment 8 Vol U.A. Kr 160 32.9 63*6 270 32.7 70.5 110 36,8 70.0 325 36.1 60.5 240 40.8 69*8 105 34.6 68 . 0 A Experiment 21 Vol U.A. Kr 220 28.6 76.5 24S 24.6 74.1 270 31.2 75*2 225 35*7 71.2 59 K\ CO CJ 73*2 225 26.7 76.8 7, 215 g honey at 8 0 ' clock, Nov. 4, 1921 8 , 200 e " 1 * 8 1 ! " 9, 1921 19, 180 g " 8 1 ) Dfic. 21, 1921 21 , 12 0 O’ 0 h 8 It Jan. 13, 1922 !• lest for sugar by Benedict's solution -23- table V I - c o nt i nu e d 4t Experiment 22 Experiment 23 Hour Vol U. A. Kr Vol U.A. Kr 7-8 350 23*7 65.7 480 29*3 64.3 8-9 170 22.2 70.9 210 25.1 71*0 9-10 245 25*7 68.5 125 27.O 69*5 10-11 345 27.1 64.6 225 31*3 73*2 11-12 125 24.6 68.5 315 27*8 63.0 12-1 205 23*5 66 .2 265 22.6 64.3 jt Experiment 24 Hour Vol U. A. Kr 7-8 375 22.6 71*2 8-9 58 27*7 69*5 1 M O 150 24.2 70.4 10-11 290 35*4 72.5 11-12 350 34.5 61.7 12-1 275 30.5 72.5 * Exp . 22, 110 23, 200 24, 200 g honey ? " 8 " 0 00 0000 -P S = aJ 'clock Jan tt ti m »» . , 18, 1922. 20, 1922 24, 1922 1* Benedict’s test for sugar I .1 -24- TABLE VII Influence of Karo Corn Syrup & * Experiment 1C Experiment 11 Hour Vol U.A. Kr Vol U.A. Kr 7-8 260 34.6 60.7 60 28.5 52.3 8-9 370 31.1 67.2 185 30,6 74.2 9-10 215 32.2 72.6 235 44.2 74. 2 1 10-11 300 29*8 66.7 105 31*3 67 . 8 1 11-12 170 26.7 67.4 50 27.4 70.2 12-1 165 25.4 690 300 27.2 69*2 & it Experiment 12 Experiment - 13 Hour Vol U.A. Kr Vol U.A. Kr 7-8 375 31*9 70.7 330 39.6 67-7 8-9 260 34.0 71*3 225 39-6 66.6 9-10 115 34.3 69. 5 1 175 33*1 71-3 10-11 35 40.3 69 • 7 1 75 27*3 66.3 11-12 35 24.2 65 * 8 205 29.0 69*8 12-1 320 26.2 70.8 95 23.0 59.5 it Exp. 10, 1Toy. 16 , 1921, 200 S at 8 o’clock 11 , 18 , 1921 310 e at 8 ” 12 , 1) 23, 1921 320 s at 8 M 13, 30, 1921 200 s at 1. Benedict’s test for sugar . ' \ -25- TABLE Vll-eontinued u. A Experiment 16 Experiment 17 Hour Vol U.A. Kr Vol U.A. Kr 7-8 330 51.0 78.6 260 35-4 66.7 8-9 130 50.1 62.1 255 31-5 71.6 9-10 125 34,8 70.0 170 30.6 72.6 10-11 240 38»8 70,8 310 32.0 69-8 11-12 390 29.4 58.0 160 29*2 6?. 2 12-1 73 31.8 61.5 200 26.1 69-5 Experiment 18 Hour Vol U» A» Kr. 7-8 250 35.2 67.6 8-9 315 31.6 67-0 9-10 145 35-4 71-5 10-11 325 32.3 69 -6 11-12 325 29-9 66.2 12-1 155 35-0 75*0 * Exp . 16, 190 17, 125 18, 200 g Karo S z " at 8 " 8 •' 8 o’clock, Eec . 9j 1921 « « 14, 1921 " " 16, 1921 'I I - 26 - TABLE VIII Influence of Cystine 4t Experiment 29 Hour Vol U.A. Kr 7-8 105 26.1 60.5 8-9 125 26.5 66 . 5 9-10 150 28.5 64.9 10-11 150 28.5 60.2 11-12 195 28.1 66.8 12-1 135 19.7 57.2 it March 8, 1922* 5 g at 8 o’clock I SUMMARY I The ingestion of glycoc oil caused an increase in endo- genous uric acid excreted. IT Fats had no apparent effect on the elimination of uric ac id » III Previous feeding of fat had no influence on the effect produced by a subsequent ingestion of glycoc oil* IV The administration of glycerol caused an increase in uric acid excretion. V The eating of honey in quantities of 100 g or more caused an increase in uric acid excretion.. VI While the consumption of small amounts of Karo corn syrup caused no apparent change laaiger amounts caused a notice- able increase in the elimination of uric acid. VII The ingestion of 5 g of cystine caused a slight rise in uric acid excretion.. - 28 - BIBLIOGRAPHY 1. Scheele, Opuscu'lar, 1776, II, 73* Cited by Benedict, S. R«, J. Lab. and Clin. Med., 1916-17, II, 1* 2. Pearson, Phil. Tr. Roy. Soc., London 1793, 15, Cited as (1)* 3. Kossel, A., Zeit. Physiol. Chem., 1879, HI, 284. 4. Burian, R., and Schuy,H., Arch. ges. Physiol., 1901, LXXXVII, 239; Zeit. Physiol. Chem., 1904-5, XLVII, 53 2 ? Arch. ges. Phys., 1900, LXXX, 308. 5. 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