E. A. (Edward Albert) Sharpey-Schäfer.

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Glutamic acid is amido-pyro tartaric acid [C3H5.(XIl2).(COOH)._,], and is
homologous with aspartic acid, being the next higher member in the series.
It occurs in minute quantities in the artificial decomposition of proteids, but
has not yet been shown to be formed in the decomposition brought about by
pancreatic digestion. It has been obtained by Eitthausen and Kreuster,^ in
the decomposition of vegetable proteid by dilute sulphuric acid ; from casein
when decomposed by stannous chloride and hydrochloric acid, by Hiasiwetz
and Habermann; - and from reticulin, by Siegfried.^

It may be obtained by saturating its ice-cold solution with hydrochloric
acid gas, and then keeping in a freezing mixture until the compound with
hydrochloric acid (05119^04-^ HCl) separates out in crystals, which are
sparingly soluble in saturated hydrochloric acid, but easily soluble in water.
N'ext, these crystals are dissolved in warm water, and the boiling solution
is treated with freshly precipitated moist silver oxide, which removes the
hydrochloric acid by forming silver chloride ; the filtrate is freed of silver
by a stream of sulphuretted hydrogen, and concentrated. On standing, glutamic
acid separates in crystals which form rhombic tetrahedra or octahedra,
sparingly soluble in cold, readily soluble in hot water, but insoluble in
alcohol or ether. Solutions of the acid are dextrorotatory (a)D = -t- 31"1,
and it shows the same phenomena with regard to rotation as are described
for leucine."*

Organic bases formed in trjrptic digestion. — Lysine and lysatine
or lysatinine. — Two organic bases, lysine and lysatine or lysatinine, have been
recently isolated from the products of artificial decomposition of proteids, by
means of a modification of the method of Hiasiwetz and Habermann, in which
metallic zinc was added in addition to stannous chloride and hydrochloric acid,
and means taken to exclude oxygen during the operation. These substances
were first isolated from casein by Drechsel,^ and afterwards extensively studied
by himself and others.'^ They have since been found among the products of
tryptic digestion.'^

Lysine and lysatine are both precipitated by a hot saturated solution of
phosphotungstic acid, which does not precipitate the amido-acids, and so
furnishes a means of separating the two from the other products of a proteid

^ Joiirn.f. 2)Talct. Chem., Leipzig, 1871, Bd. iii. S. 314.

^ Ann. d. Chem., Leipzig, 1873, JM. clxix. S. 150.

^ "Habilitationsschiirt," Leipzig, 1892. •* See p. 423.

^ Arch. f. Pliysiul., Leijizig, 1891, S. 254; Ber. d. deutsch. chem. Gesellsch., Beiliii,
1890, Bd. xxiii. S. 3096.

" E. Fisclier, Arch. f. Physiol., Leipzig, 1891, S. 265 ; Max Siegfried, Ber. d. deutsch.
chem. Gesellsch., Berlin, 1891, Bd. xxiv. S. 418 ; Arch. f. Physiol., 1891, S. 270; S. _G.
Hedin, ibid., 1891, S. 273 ; Drechsel and Krliger, Bcr. d. deutsch. chem. Gesellsch., Berlin,
1892, Bd. XXV. S. 2454.

^ Hedin, Arch. f. Anat. ?/. Physiol., Leipzig, 1891, S. 273.


decomposition. Lysine forms a platinochloride (C^H^^^ISr^O^, H^PtClg +
C^HjOH) which is insoluble in 50 per cent, alcohol, in which the corre-
sponding lysatine salt is soluble, and by this means the two bases may be
separated ; or they may be separated by means of the difference in solubility
of their silver salts. ^

Lysine, C|3Hj4lS^20o5 in composition corresponds to a diamido-caproic acid
(C5Hg(jSrH,^)2COOH) ; its solutions are dextrorotatory, but, like leucine and
glutamic acid, become inactive when heated with baryta water to LSO" C. The
salts of lysine are crystalline, but the base itself has not been obtained in a
crystalline form.

Lysatine or lysatinine yields a crystalline silver salt of the composition
CgH^gA^gOg, HNOg + AgNOg, from which the formula of the base follows as
CgH^^gNgO.,, except, as is supposed probable, the silver salt contains a molecule
of water of crystallisation, in which case the formula of the base would be
CgH-^^NgO. With the former formula it would be homologous with creatine,
with the latter homologous with creatinine, and would be most properly
called lysatine or lysatinine accordingly.

Creatine is C^HriJ^gOg and creatinine is C^H-lSTgO. The new base may be
either lysatine with the formula CjjHjglSTgOg, or lysatinine with the formula
C^jH^jNgO ; in either case being the second higher number in a homologous
series, that is differing in formula by (CH2)2-

Another similarity to creatine invests this organic base with its most
important physiological interest. Creatine when boiled with baryta water
splits up into sarcosin (or methyl-giycocoll) and urea ; similarly treated,
lysatine also yields urea. Drechsel treated the lysatine obtained from
10 grms. of the silver salt above referred to with excess of baryta water,
and obtained 1 grm. of urea nitrate, from which he isolated and identified
the urea. This is all the more interesting from the fact that creatine,
although it occurs in the body under such circumstances as leave little
doubt that it is formed as a decomposition product of proteids, has not
yet been obtained artificially as a direct product of proteid decomposition,
Lysatine has not only been so obtained, but also as a product of pancreatic
digestion, and urea having been obtained from this, has consequently been
obtained as a product of proteid decomposition.

Hedin ^ obtained from 3 kilos, of moist fibrin, 28 grms. of pure platino-
chloride of lysine, and enough of the silver salt of lysatinine to establish
its identity.

Ammonia is found as a constant product in the artificial decomposition of
proteids, as might be inferred from what has been stated concerning lysatine,
and its formation has also been shown in pancreatic digestion. Hirschler ■^
has shown that in the entire absence of putrefaction, in so short a jDeriod as
four hours, small quantities of ammonia appear in the pancreatic digestion of
fibrin ; this result has been confirmed by Stadelmann.*

The chromiogen of pancreatic digestion. — As early as 1831 it was
observed, by Tiedemann and Gmelin,^ that the pancreatic juice of the dog takes
on a rose-red colour when mixed with chlorine water. Claude Bernard next
showed that no such reaction is obtained with fresh pancreatic juice, but first
appears after the juice has been kept for some time without putrefaction setting
in ; if putrefaction takes place, the reaction is also not obtained. The product
giving this colour reaction is now definitely recognised as a product of pancreatic
digestion, and not a constituent of pancreatic juice. For it the name trypto-

-^ For details of these processes see Gamgee, "Physiological Chemistry," London, 1893,
vol. ii. p. 255.

^Arch.f. Anat. u. Physiol., Leipzig, 1891, S. 273.

^ Ztschr. f. x)Tiysiol. Chem., Strassburg, 1880, Bd. x. S. 302.

^ Ztschr.f. Biol., Mliuchen, 1888, Bd. xxiv. S. 261.

^ "Die Verdauung nach Versuchen," Heidelberg, 1831.


phan has been suggested, by jSreumeister,^ from the pomt of view that
it may be made to serve as an indicator of when tryptic digestion has
reached a certain stage and amido-acids are beginning to be formed,- since
it first appears in the more advanced stages of proteid decomposition simul-
taneously with the amido-acids. Tryptophan has never been isolated, and is
only known by its colour reactions. When not very dilute, the rose-red colour
is replaced by violet, and Kiihne has shown that the colour is given by
bromine water as well as by chlorine water. According to Krukenberg,^
the colour is not due to oxidation by the chlorine or bromine, but to the
formation of an addition compound ; he also states that tryptophan is
slightly soluble in alcohol, ether, and chloroform. Hemala^'^has shown that
the coloured material is easily soluble in amyl alcohol. Here chlorine and not
bromine water must be used as a test, for the latter itself imparts colour to
amyl alcohol. When much peptone or other impurity is present with it in
solution, it falls, after some time, as a precipitate ; this on shaking np with
alcohol gives a fine violet solution showing an absorption band at the
D line. According to Krukenberg, a strong coloration is given even by
traces of the chromogen ; he also has shown that tryptophan is diffusible.

In its reaction with bromine and chlorine water, tryptophan closely
resembles the chromogen of the suprarenal gland ; the two chromogens are
also alike in being diffusible and in tbeir powerful tinctorial action, but here
resemblance ceases. The chromogen of suprarenals is very easily destroyed by
alkalies, could not be formed in pancreatic digestion, and is quite insoluble in
dry alcohol, ether, or chloroform.

Kiihne has shown that tryptophan is a constant product in all proteid
decomposition, but that it is rapidly destroyed and disappears ; it is also
rapidly destroyed by putrefactive changes.

When pancreatic digestion is accompanied by putrefaction, many other
substances are formed besides those above described. These will be considered
in connection with bacterial digestion in the intestine.

Digestion of Various Bodies allied to the Peoteids.

Those substances, such as the mucins and nucleo-proteids, which
consist of a proteid molecule united to some organic radicle (and called
Proteide by Hoppe-Seyler), first undergo a cleavage into proteid and the
body involved with it ; the proteid is then digested in the usual fashion,
while the other substance very often suffers no change. In this manner
haemoglobin is decomposed by peptic digestion into a proteid commonly
supposed to be a globulin, which becomes converted through albumose
into peptone, and htematin which remains unchanged. Nucleo-proteids
and nucleo-albumins ^ yield on similar treatment an insoluble residue
of nuclein, or of pseudo-nuclein or paranuclein respectively, and the
proteid part of the molecule is peptonised. In the tryptic digestion of
fibrin some of the xanthin bases (or nuclein bases) have been found ;
these arise from the breaking up of nuclear-nuclein (Kernmwlein)
present as a constituent of admixed nucleo-proteid, derived from the
nuclei of white blood corpuscles. The nuclein breaks up into nucleic

1 Ztschr.f. Biol., Munchcn, 1890, Bd. xxvii. S. 309.

" The name proteinochromogen has been given to this chromogen by Stadehiiann,
ihicL, 1890, 15d. xxvi. S. 491.

* Krukenberg, Virchoufs Archiv, 1885, Bd. ci. S. 555; Vcrhandl. d. phys.- med.
GeselUch. zu Wilrzhurg, 1884, S. 179.

^ Loc. cit. See also Neunieister, Ztscltr. f. Biol., Miinchen, 1890, Bd. xxvi. S. 332.

^ jSTuoleo-proteids yield on decomposition a true nuclein, containing nucleic bases,
nucleo-albuniins a pseudo-nuclein or paranuclein, which does not contain such bases.


acids and proteid, and the nucleic acids in their turn into nuclein bases
and phosphoric acid. These changes take place very slowly in tryptic
digestion. On digestion with pepsin and hydrochloric acid, the glyco-
proteids are decomposed, yielding a carbohydrate substance which
reduces Fehling's solution and a proteid which as before is peptonised.
This decomposition only takes place slowly, and is probably due in
great part to the feeble hydrolytic action of the hydrochloric acid.

The caseinogen of milk is first coagulated by the action of the rennin
of the gastric juice, and afterwards the insoluble casein formed in this
process is digested.

Casein is broken up in the process of gastric digestion into a proteid
and pseudo-nuclein, of which the former is changed into peptone, while
the latter is thrown out as an insoluble precipitate.

This precipitate corresponds to the dyspeptone of Meissner, and has been
the subject of a considerable amount of investigation. Lubavin ^ found that
it contained inorganic phosphorus, and that it is a mixture of which one part is
sohible in dihite sodic carbonate (Na^COg), while the other is insoluble. The
soluble part contains 4'6 per cent, of phosphorus, and is probably identical
with Hoppe-Seyler's nuclein. Chittenden ^ and others state that dyspeptone does
not contain much phosphorus, and that this is probably present as calcium
phosphate, dyspeptone being therefore not a nuclein but a mixture of calcium
phosphate with a hydration product of casein. C. AVildenow ^ does not hold
with this view, having obtained dyspeptone which contained only 0"13
per cent, of calcium, and 3*85-4'66 per cent, of phosphorus, but agrees with
Lubavin that the precipitate is a nuclein. E. Salkowski ^ supports this con-
clusion ; he also announces that on prolonged digestion the precipitate
redissolves to a clear solution, part of the phosphorus being split off as
phosphoric acid, and part remaining in organic combination (probably as
paranucleic acid). Such a solution can be brought about, according to
Salkowski, by a strong peptic solution within forty-eight hours.

The albuminoids as a class are fairly resistant to the action of
digestive agents ; when they are broken up, they yield products closely
resembling those furnished by the decomposition of the true proteids.

Collagen is said to be converted into its hydrate gelatin more
rapidly by the action of pepsin and hydrochloric acid than it would be
by the acid alone ; the gelatin thus formed is then acted upon by the
pepsin and hydrochloric acid, and rapidly loses its characteristic property
of gelatinising on coohng.^ This physical change is the visible sign of a
chemical one, by which the gelatin is converted into a substance called
protogelatose ; this is again changed, yielding deuterogelatose ; and finally
gelatin peptone is formed.'' These substances resemble the corresponding
compounds of proteid digestion, the gelatin peptone being distinguished
from the other two products by its indifference to the saturation of its
solutions with neutral salts and by its diffusibility. Protogelatose is
thrown out of solution by saturation of its acidified solution with sodium

'^ Med.-chem. Untersueh., Berlin, 1S71, S. 463.

^ Stud. Lab. Physiol. Chem., New Haven, 1890, vol. iii. p. 66.

^ luaug. Diss., Bern, 1893.

■* Ccntralbl. f. d. med. Wlssensch., Berlin, 1893, ISTos, 23, 28; Arch. f. d. ges. Physiol.,
Bonn, 1896, Bd. Ixiii. S. 401.

^ J. de Bary, Ztschr. f. fhysiol. Chem., Strassburg, 1896, S. 75 ; Etzinger, Ztschr. f.
Biol., Mitnchen, Bd. x. S. 84 ; Uffelmann, DeuUches Arch. f. klin. Med., Leipzig, Bd. xx.
S. 535.

•^ Chittenden and Solley, Journ. Physiol., Cambridge and London, 1891, vol. xii. p. 23.


chloride, while cleuterogelatose is only precipitated by saturation with
ammonium sulphate. Protogelatose is also precipitated by platinic
chloride, while deuterogelatose is not so precipitated.

Collagen is not attacked by pancreatic juice unless it has been
pre^'iously boiled with water, or swollen by the action of dilute acids, as
it normally would be by the gastric juice.^ This result is confirmed by
the observation of Ludwig and Ogata, that after removal of the stomach
proteid was still digested, but connective tissue was not attacked. After
such preliminary treatment collagen is easily converted into gelatin,
and the after com'se of events closely resembles that described for
peptic digestion. There is first formed protogelatose, then deutero-
gelatose, and finally gelatin peptone, which is not converted by any
further action of trj^Dsin into amido-acids.^ Trypsin acts so easily on
gelatin, and deprives it so readily of its power of gelatinising, that this
has been recommended by Fermi as a test for trypsin.^

The decomposition products of gelatin have been long known, though not
with the exactitude above described. Gmehn showed that it was decom-
posed by superheated steam at 140° C, and Hof meister '^ obtained, after boil-
ing with water in 1 per cent, solution for thirty hours, two cleavage products
which he termed semiglutin and semicollin ; these are probably identical with
proto- and deuterogelatose.

Elastin is also dissolved by pepsin and hydrochloric acid,^ though
with more difficulty than collagen. The products of the peptic digestion
of elastin were studied by Horbaczewski,^ who described two products
which he called hemielastin and elastin j)ex3tone. The same subject has
been investigated more recently by Chittenden and Hart,^ who have
shown that two substances are formed in the peptic digestion of elastin,
but that both these substances are albumoses, since they are both pre-
cipitated by saturation of their solutions with ammonium sulphate ; to
these substances they gave the names of protoelastose and deutero-
elastose. The former is precipitated on saturation of its solution with
sodium chloride, while the latter is only precipitated on the addition of
acetic acid. Elastin is also directly attacked by trypsin and dissolved,
forming in tium proto- and deuteroelastoses as in peptic digestion, but
neither in peptic or tryptic digestion is there any peptone formed.^

1 Ewald and Kilhne, VerhancU. d. naturh.-med. Ver. zu Heidelberg, 1877, IST. F.,
Bd. i. S. 4.51.

^ Chittenden and Solley, loc. cit.

^ Arch. f. Hyg., Miinciien u. Leipzig, 189], Bd. xii.

■^ Ztschr. f.fUjsiol. Chevi., Strassburg, 1878, Bd. ii. S. 299.

■"' Etzinger, Ztschr. f. Biol., Mlinchen, Bd. x. S. 84.

'^ Ztschr. f. jjhysiol. C'hcm., Strassbnrg, 1882, Bd. vi. S. 330.

'^ ZtscJir.'f. Biol., Mlinchen, 1889, Bd. xv. S. -368.

® Chittenden and Hart, loc. cit.



It was for many years believed that the absorption of the products of
digestion from the alimentaiy canal was governed by exactly the same
physical laws as determine the passage of a solution and its dissolved
constituents through an inert membrane, but the accumulation of
experimental evidence has rendered such a belief no longer tenable.
It is now known that the cells which line the alimentary canal take an
active part, not only in absorbing the materials prepared for them by
the action of the digestive secretions, but in modifying these products
in various ways during the process.

Before the laws of diffusion of solutions were known, the process of
absorption by the columnar cells of the intestine was compared by Tiedemann
and Gmelin (1820) ^ to that of gland secretion. After the establishment of the
laws of diffusion, attempts were made to apply them in explanation of absorp-
tion, as well as of other similar processes in the body. Such physical views
persisted for a long time, imtil it was shown by conclusive experiments that
absorption, like these other processes, does not obey the laws of physical
diffusion, but is selective in its character and governed in some subtle way
by the activity of the cells involved. Our modern view is thus, as is often
the case, a recurrence to an older theory ; the only difference being that we
have a somewhat broader experimental basis on which to build it.

The cells of a secreting gland take up certain materials from the lymph in
which they are bathed, and from these, in some manner, elaborate certain
products which are passed into the gland lumen as a secretion. Similarly, the
absorbing cells of the intestine take up certain products of digestion from
the intestinal contents by which they are bathed, and build up from these
certain materials which pass into the lymph. So that absorption may be
regarded as a kind of reversed secretion.

In both cases the process is a selective one, the constituents of the gland
secretion are definite in their nature, in many cases specific, and are probably
formed from definite constituents of the lymph taken up by the secreting cell
to the exclusion of others. In like fashion, certain materials only are taken
up by the epithelial absorbing cell, and from these definite products are
formed to be passed into the lymph.

That absorption is a selective process and not one of purely physical
diffusion, is shown by the following observations : —

1. Certain colloids {e.g. alkali albumin) disappear from the intestine
at a fairly rapid rate, even in the complete absence of digestive

2. The rate of absorption from the intestine of various dissolved
substances is not proportional to their diffusion-coefficients. Sodium
sulphate is much more diffusible than grape-sugar, but wdien a solution
containing 0-5 per cent, of each of these is injected into the intestine,
the sugar disappears much more rapidly, and only traces of it remain
at a time when the greater part of the sodium sulphate is still left

3. The rapidity of absorption is much greater than can be accounted

1 Quoted by Heidenhain, Arch. f. d. gcs. Physiol., Bouu, 1888, Supp. Heft, Bd.
xliii. S. 69.

" See form of absorption of proteids, p. 436.

3 Rohmann, Arch. f. d. ges. Physiol., Bonn, 1887, Bd. xli. S. 411.


for, on the basis of xjhysical diffusion from the intestinal contents to the

4. If the dissolved products of digestion are carried through by
diffusion, it must be passively in a diffusion stream due to salt diffusion,
their own diffusive powers being too feeble to suppose they are carried
by these. ISTow, not only would such a stream be too slow, but, in such
a case, the amount of fluid which must be absorbed by the epithelial
cells would be enormous. There is at tlie height of proteid digestion,
even in an animal with such digestive powers as t"he x^ig, rarely more
than 2 per cent, of albumoses and peptones together in solution in the
intestine, and usually much less. If it be supposed that this is passively
and not selectively absorbed, then to carry 100 grms. of digested proteid
out of the intestine, 5 litres of water at least, and probably a great
deal more, would be required. During the digestion of starch, only
traces of sugar are found at any given time in the intestine, and
generally it may be stated that absorption takes place from very dilute
solution. There is no reason to believe that such enormous quantities
of fluid are thrown into the intestine during digestion, to be afterwards
absorbed from it, and hence it must be concluded that dissolved
substances are not passively absorbed by their solutions passing
unchanged into the epithelial cell.

Seat of absorption.— Absorption of some substances begins in the
stomach,^ but the main part takes place in the intestine. Water is
practically not absorbed at all in the stomach,^ while alcohol is readily
taken up. The absorption of chloral hydrate and of sugar by the
stomach is increased by the presence of alcohol.

Gastric absorption is said to be increased Ijy greater concentration of
the substance to be absorbed, while the reverse holds for intestinal
absorption. A solution of grape-sugar is most rapidly absorbed from
the intestine when its concentration lies at 0-5 per cent. ; as the
concentration increases from this the rate of absorption diminishes ;
while the rate of absorption in the stomach increases up to a concen-
tration of 20 per cent.* According to v. Mering, all forms of sugar are
absorbed in the stomach to a greater or less extent. The products of pro-
teid digestion are also probably absorbed to a slight extent in the stomach.^

Channels of absorption.— The new materials formed by the action
of the intestinal epithelial cells on the absorbed products of digestion,
pass out of these cells into the lymphoid tissue of the villus underlying
them. The modified carbohydrates and proteids pass in solution into
the lymph which bathes the tissue, and in soluble form are absorbed
from this lymph by the capillary vessels of the villus, thus passing
directly into the portal circulation, while the fats leave the epithelial
cells as fat globules, and are carried as such past the capillary network
of the villus, to enter the lacteal situated in the axis of the ^dllus.*^

^ Heidenhaiu, Arch. f. d. ges. Physiol., Bonn, 1888, Supp. Heft, Bd. xliii. S. 70.

- See Busch, Vi/rchov/s Archiv, 1858, Bd. xiv. S. 171 ; Tappeiner, Ztschr. f. Biol.,
Miinchen, 1880, Bd. xvi. S. 497 ; v. Anrep, Arch. f. Anat. u. Physiol., Leipzig, 1881,
S. 504 ; Meade-Smith, ihid., Leipzig, 1884, S. 481 ; v. Mering, Verhandl. d. Cong. f.
wmere ifec?. , AViesbaden, 189-3; Ccntralhl. f. Physiol., Leipzig u. Wieu, 1893, Bd. viii.
S. 53.3.-

" Edkins, Joicni. Physiol., Cambridge and London, 1892, vol. xiii. p. 445 ; v. Mering,
loc. cit.; Gley and Rondeau, Com2)t. rend. S'oc. de. bioL, Paris, 1893, p. 516.

* Brandl, Ztschr. f. Biol., Miinchen, 1892, Bd. xxix. S. 277.

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 61 of 147)