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proportional to the exposed area of the cleavage products of various proteids apanimal.
pear distributed as shown in the following Even in pathological conditions a re- table.2 markable constancy of total heat produc
COMPOSITION OF PROTEID. tion is apparent. Thus in such typical disturbances as anæmia, diabetes, gout and obesity, the general laws governing the output of carbon dioxide, the absorption of oxygen and the production of heat are
16.5 found to be the same as in health. In fever the metabolism and heat production
Phenylalanin increase and this to a certain extent on
4.43 account of the warming of the cells. In exophthalmic goiter. there is probably an
Oxy-y-Pyrrolidin carboxincrease in metabolism, due to the chemical stimulus of an excessive production of List: iodothyrin in the thyroid gland, while in
Tryptophan. myxædema the absence of the same substance causes a considerable reduction in the metabolism. Drugs may influence the
The proteid metabolism in plants and course of the metabolism, iodothyrin in
animals occurs in striking similarity to the creasing it and morphine profoundly di
changes brought about by enzymes and minishing it, but on the whole the most
hydrolytic agents acting on proteid outstriking fact is not the variability, but
side of the tissues. Thus in the germinrather the uniformity, of the processes con
ating seed Schultze finds that asparagin, cerned.
leucin, tyrosin, histidin, arginin and lysin Within recent years the work of Kossel,
arise from the metabolism of proteid. The Fischer, Hofmeister and Levene has given
occurrence of leucin and tyrosin in the a more definite conception of the composi
liver and urine in such diseased conditions tion of proteid than was before possible. as phosphorus poisoning has long been There is every indication that the proteid known and Abderhalden and Bergell* remolecule consists fundamentally of groups
port the presence of glycocoll in rabbit's
port the presence of of amino fatty acids banded together. urine after the administration of phosProteids vary with the integral components
phorus. Urine after phosphorus poisoning of their chemical chains. It has long been may also contain phenylalanin and arknown that the end products of tryptic
ginin.& Wakeman? finds an altered quandigestion include such substances, but
Abderhalden, E., Zeitschr. f. physiol. Chem.,
1905, Bd. 44, p. 17. Kutscher first showed that continued tryp
3 Schultze and Castero, Zeitschrift für physiotic digestion resulted in the complete trans- logische Chem., 1904, Bd. 44, p. 455. formation of proteid into these amino-acids. • Abderhalden and Bergell, Zeitschrift für Cohnheim discovered erepsin, an enzyme physiologische Chem., 1903, Bd. 39, p. 464. derived from the intestinal wall. which • Abderhalden and L. F. Barker, Zeitschrift für rapidly converts albumoses into these sub
physiologische Chem., 1904, Bd. 42, p. 524.
Wohlgemuth, Zeitschrift für physiologische stances.
Chem., 1905, Bd. 44, p. 74. On chemical analysis, using methods de- Kossel, Berliner klinische Wochenschrift, 1904. veloped in Emil Fischer's laboratory, the No. 41.
titative relationship between histidin, ar- produced in the mucosa as well as from that ginin and lysin in the composition of liver which normally originates in the intestine substance after phosphorus poisoning, ar- during tryptic proteolysis. ginin in particular being reduced below The existence of denitrogenizing enthe quantity found in the liver of the nor- zymes is afforded by the example of the mal dog. This possibly suggests a specific guanase and adenase of Walter Jones, 11 action by phosphorus on certain cell pro- which respectively convert guanin into teids rich in arginin which are essential to xanthin and adenin into hypoxanthin with vitality. All forms of proteid decomposi- the liberation of ammonia. tion follow, therefore, the pathway of Folin believes that the greater part of cleavage into amino acids.
the proteid ingested undergoes a denitroThe question arises, to what extent may genization through the hydrolysis of the the amino bodies formed within the in- amino cleavage products. Such a reaction testine be regenerated into proteid? It is would read believed that the cells of the intestinal vil
CNH, + H,0= COH+NH. lus regenerate fat from fatty acid and glycerin, since neutral fat alone is found
The ammonia may be converted into urea in the thoracic duct. But all the starch
within the organism, and the nitrogen free fed is not regenerated into starch, nor is
rest may be converted into sugar. The maltose regenerated into maltose in the simplest expression of this is seen in the body. Much may be burned as dextrose
experiment of Neuberg and Langstein,12 and only a part is transformed into gly. who found glycogen in the liver and lactic cogen. Long ago Schultzen and Nencki acid in the urine of a rabbit following the stated that a certain amount of amino ingestion of alanin. The transformation bodies formed in digestive proteolysis was of alanin into lactic acid may be written absorbed and burned, and that the ab- CH, CHNH: COOH + 1,0= sorbed proteid itself followed the lines of
CH, CHOHCOOH +NH,
Alanin. an enzymatic cleavage into amino bodies.
Lactic Acid. In the light of newer knowledge several
The transformation of lactic acid into authorities have recently elaborated theo- sugar is demonstrated by the experiment ries along similar lines. It has been point- of A. R. Mandel,1% who showed an increase ed out by Folin' that there is little evidence in the sugar output in diabetes after the of reconstruction of all the proteid in- ingestion of lactic acid. gested. He cites the experiments of Stiles and Lusk14 have shown that ingesXencki and Zaleski,10 which showed that tion of the mixture of amino bodies prothe portal blood during digestion contains duced from the tryptic digestion of meat four times as much ammonia as arterial may yield sugar in large quantity in diablood, and that the mucosa of both stomach betes. and intestine yield large quantities of am- 11 Jones and Winternitz, Zeitschrift für physiomonia. The inference is that the ammonia logische Chemie, 1905, Bd. 44, p. 1. of the portal vein is derived from ammonia 12 Neuberg and Langstein, Archiv für Physiol.
Schultzen and Nencki. Zeitschrift für Biologie. ogie, Suppl. Bd., 1903, p. 514. 1872, Bd. 8, p. 124.
13 Mandel, “Proceedings of the American PhysioFolin, American Journal of Physiology, 1905,
logical Society,' Am. Jour. of Physiol., 1905, Vol. Vol. 13, p. 117.
13, p. xvi. * Vencki and Zaleski, Zeitschrift für physio
34 Stiles and Lusk, American Journal of Physiol. logische Chem., 1901, Bd. 33, p. 206.
ogy, 1903, Vol. 9, p. 380.
Wolf15 finds that none of these amino the endogenous nitrogen. To what extent, substances has any effect on the blood press if any, urea nitrogen enters into this essensure of animals, so far as he has examined tial life metabolism he is not prepared to them.
say. The same idea was expressed by Although some proteid metabolism may Burian"? in an article published ten days take place as above outlined, it is an un- later than Folin's. Burian believes that doubted fact that proteid may be synthe- purin bases are a constant product of sized in the body with the formation of new muscle metabolism and that these are oxitissue, and also that proteids injected into dized to uric acid, a part of which is furthe blood stream, as in cases of transfusion ther converted into urea. This process of of blood serum, are rapidly destroyed and itself would evolve urea as a constant the nitrogen eliminated as urea. The con- product of the endogenous nitrogen metabditions of proteid metabolism may, there- olism. According to this newer conception fore, be entirely similar to those of starch the cells of the body through the swingmetabolism, (1) digestive hydrolysis, (2) ing motion of their particles do continupartial combustion of the end products, ally break down their own protoplasm with and (3) possible regeneration of portions the production of creatinin, purin bases, of the end products into substances similar and perhaps other substances. These same to the originals, but characteristic of the cells may also break up exogenous amino organism, i. e., glycogen and body proteids. radicles derived from ingested proteid or In the case of proteids the second or meta- circulating proteid itself. bolic process involves the partial passage of Neuberg and Loewi18 have made an obthe end products through the glucose stage. servation which is not in accord with the The third or regenerative process is pro- idea that proteid metabolism normally moted by such a proteid as casein, which passes through the amino-acid stage. These yields a variety of cleavage products. authors investigated a case of cystinuria, a Folin18 has discovered that a man fed
condition in which cystin formed from with creatin free food eliminates a constant
proteid can not be burned, but is elimiquantity of creatinin nitrogen in the urine nated in the urine. After ingesting leucin, irrespective of the amount of nitrogen in
tyrosin and aspartic acid these also were gested with the food. Thus the urine of
almost quantitatively eliminated in the paone man contained 16.8 grams of total ni- tient's urine, although
tient's urine, although the normal organtrogen with 0.58 gram of creatinin nitro
ism burns them. Since these substances gen. The same man at another time, after
were not eliminated by the patient on a large carbohydrate ingestion, eliminated
normal diet, the presumption is that they 3.60 grams of total nitrogen and 0.60 gram
can not be normal products of intermediary of creatinin nitrogen. Folin conceives that proteid metabolism. The authors find it the constancy of the creatinin and uric
difficult to explain this according to the acid output is a true index to the neces
conception of a general breakdown of prosary protoplasmic breakdown, and would
teid into amino acids. This experiment define the nitrogen of such destruction as lacks confirmation.
15 Wolf, Journal of Physiology, 1905, Vol. 32, 27 Burian, Zeitschrift für physiologische Chem., p. 171.
1905, Bd. 43, p. 532. 1e Folin, American Journal of Physiology, 1905, 18 Neuberg and Loewi, Zeitschrift für physioVol. 13, p. 66.
logische Chemie, 1904, Bd. 43, p. 338.
As regards fat metabolism Geelmuyden1 Rubner24 gives the following theory of is inclined to the opinion that oxybutyric metabolism: Living proteid, through the acid, aceto-acetic acid and acetone are nor- vibrations of its particles, metabolizes the mal metabolism products derived from food substances. The action resembles members higher up in the series.
catalysis. The energy liberated reacts on As regards dextrose Stoklasa 20 announces the particles of protoplasm, causing a that all animal and vegetable cells contain change in their position and a cessation of enzymes capable of converting dextrose metabolism. The particles then return to into alcohol and carbon dioxide. He21 also their original position and the cycle begins finds a ferment in animal tissues able to again. These processes require a fixed convert sugar into lactic acid. He quotes amount of energy. Rubner does not give Oppenheimer's experiment, showing that his reasons for believing in this rhythm of whereas fresh normal blood yielded little excitation and rest. lactic acid on standing at 37° C., much T he quantity of the combustion depends greater amounts were formed if dextrose on the power of the cells to metabolize was added. He believes that this lactic (Voit). In the resting state this metabolic acid is subsequently converted into alcohol power of the cells is influenced by the 'law and carbon dioxide.
of skin area' (Rubner). Temperature Embdeno2 comes to the conclusion that (cooling or warming) and nerve excitation blood sugar perfused through the liver may (muscle work, chemical regulation) affect be broken up into lactic acid. It has been the power of the cells to metabolize, per
converted into dextrose and it is a curious of the particles, an effect which is in turn fact that this same dextrose may pass maintained at the expense of the energy through the lactic-acid stage on its way to derived from metabolism. Living protooxidation.
plasm metabolizes in accord with its necesA. R. Vandel23 in the writer's laboratory sities at the time, and never more. Large has shown that lactic acid disappears from quantities of nutrient materials furnished the blood and urine in phosphorus poison- will not increase cell metabolism. If food ing if diabetes be induced. Here the be ingested above the requirement for the mother substance of the accumulating lactic organism, any excess will be retained in the acid is removed in the urine. Any con- body. The kind of metabolism depends siderable production of alcohol in tissue upon the constitution of the fluid feeding metabolism, while possible, does not seem the cells, and whether proteid, carbohyprobable in light of the known physiolog. drates or fats have been ingested. ical action of the substance.
Each ingested foodstuff exerts a specific 13 Geelmuyden, Zeitschrift für physiologische dynamic action (Rubner). At a temperaChem., 1904, Bd. 41, p. 128.
ture of 33° C. the ingestion of the starva* Stoklasa, Centralblatt für Physiologie, 1903, tion requirement of energy in the form Bd. 17, p. 465. 31 Stoklasa, Jelinck und Cerny, Centralblatt für
of fat increases the requirement for energy Physiologie, 1903, Bd. 16, p. 712.
ten per cent., carbohydrates raises it five per - Embden, “Verhandlungen der 6sten Interna
cent., proteids thirty per cent. In other tionalen physiologen ('ongress, Centralblatt für
words, in the case of meat, in order to obPhysiologie, 1905, Bd. 18, p. 832.
- Vandel, · Proceedings of the Am. Physiol.. So. tain calorific equilibrium about 140 calories ciety,' American Journal of Physiology, 1905, Vol. 2* Rubner, “Von Leyden's Handbuch der Ernäh13, p. xvi.
ungstherapic, 1903, p. 78.
must be ingested instead of 100, if that represents the starvation requirement. Rubner25 explains that the cells of the body do not require more energy after meat ingestion than in starvation, but that the heat produced by a preliminary cleavage of proteid into dextrose on the one hand, and into a nitrogen containing rest on the other, while yielding heat to the body does not furnish the actual energy for the vital activities of the protoplasm. This is furnished principally by the dextrose derived from the proteid. Although it is necessary to abandon the older theory which pronounces glycogen (or dextrose) a direct cleavage product of proteid, still the explanation of Rubner remains tenable if interpreted in the newer light. If the energy requirement of the cell remains constant at 100, even after the ingestion of 140 calories of proteid, then 71.4 per cent. of the total heat value of the proteid is the quantity actually used for the vital processes. Since it has been shown in the writer's laboratory that meat proteid yields 58 per cent. of dextrose in metabolism, it may be calculated that 52.5 per cent. of the total energy of proteid may be available for the cells in the form of sugar. A balance of 19 per cent. must be obtained from other compounds, while 28.5 per cent. of the total heat value is wasted as heat without ever having been brought into the service of the life processes of the cells. Perhaps this 28.5 per cent. of heat loss represents the quantity produced by the cleavage of proteid into amino bodies and the denitrogenization of these radicles.
The constancy of the energy requirement in metabolism makes difficult the explanation of the action of the various ferments found in the body. These are of two varieties, hydrolytic and oxidizing, but these from the very principles of our
25 Rubner, 'Gesetze des Energieverbrauchs,' 1902, p. 380.
knowledge must be subservient to the requirement of the living cells, and not themselves masters of the situation, as, for example, they are in the autolysis of dead tissue. It seems to be the requirement of the mechanism of cell activity which determines metabolism, and not primarily the action of enzymes, whose influence appears to be only intermediary.
Friedenthal26 shows that proteid, colloidal carbohydrates, fats and soaps are not oxidizable in the cellular fluids without previous hydrolytic cleavage. After hydrolysis, however, the oxidases may effect an oxidation of the smaller molecules. The necessity of the hydrolytic ferment is seen in the non-combustion of dextrose after the extirpation of the pancreas, the organ by which the ferment is supplied. Oxygen and the oxidases are present in ample quantity, but the sugar is not burned unless it be broken by its specific ferment. In the meantime the cell avails itself of a compensatory energy supply from other sources. It is impossible to apply anything similar to Ehrlich's side-chain theory to this condition of affairs, for the metabolism does not depend upon the satisfaction of chemical affinities, but rather upon a definite law of utilization of energy equivalents.
However clearly formulated the laws of metabolism may be, and many of them are as fixed and definite as are any laws of physics and chemistry, still the primary cause of metabolism remains a hidden secret of the living bioplasm.
GRAHAM LUSK. UNIVERSITY AND BELLEVUE HOSPITAL MEDICAL COLLEGE.
SCIENTIFIC BOOKS. Notes on Anthropoid Apes. By the Hon.