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processes, in passing them on to the lymph spaces of the villi ; that, in
fact, cellular digestion of absorbed carbohydrates may take place in the
epithelial cells after absorption.

Tlie secretion of the small intestine is generally stated to be
inactive towards lactose, so that the inversion of this sugar probably
occurs after its absorption by the columnar cells.'i

Human succus entericus has been investigated by Ewald,^ by Demant,''
and by Tubby and Manning \ '^ they all agree as to its diastatic action on starch
and inverting action on cane-sugar. Tubby and Manning also tested its action
on maltose, and found that this was converted into dextrose. The ferment or
inverting material adhered to mucus whenever a precipitation of this took
place in the fluid, so that the mucus was more effective than the clear
fluid.s



DIGESTION. OF PEOTEIDS.

The digestion of proteids is a much more complex process than that of
either the fats or carbohydrates, and one of which our knowledge is still
less exact. In the digestion of carbohydrates we are absolutely certain
that we have to do with a hydrolytic process, and that from a body
of absolutely fixed percentage composition, though often of unknown
molecular weight, there is produced in digestion a substance of known
formula, and to a certain extent of known structure. In proteid digestion,
while it is probable that a very similar action is taking place, we have
no such certainty. The digestive process begins with material, the
different proteids, which varies considerably in percentage composition.

^ Ztschr.f. Biol., Mlinchen, 1895, Bd. xxxii. S. 266.

^ Proc. Roy. Soc. London, 1880, vol. xxx. p. 399. See also Sliore and Tebb, Journ.
Physiol., Cambridge and London, 1892, vol. xiii. {Proc. Physiol. Soc), and M. C. Tebb, ibid,
vol. XV. p. 421.

^ Rohmann, Arch. f. d. ges. Physiol., Bonn, 1887, Bd. xli. S. 424.

^ Meyer, "Die Lebre von den cliemiscben Fermenten," 1882 ; Dastre, Arch, de pliysiol.
norm, etpath., Paris, 1890, tome xxii. p. 103 ; C. Voit and Lusk, Ztschr. f. Biol., Mlinchen,
1891, Bd. xxviii. S. 275 ; Mendel, Arch. f. d. ges. Physiol., Bonn, 1896, Bd. Ixiii. S. 425.
See, however, Pautz and Vogel, Ztschr. f. Biol., Mlinchen, 1895, Bd. xxxii. S. 304 ; Rohmann
u. Lappe, Ber. d. deutsch. diem. Gesellsch., Berlin, 1895, Bd. xxviii. S. 2506.

5 Virchow's Archiv, 1879, Bd. Ixxv. S. 409. « Ibid., S. 490.

"^ Guy's Hosp. Pi.ep., London, 1891, vol. xlviii. p. 271 ; Centralbl. f. d. med. JFissensch.,
Berlin, 1892, S. 945.

^ Paschutin {loe. cit.) found that the inverting enzyme was mechanically precipitated
along with collodion.



400 CHE MI ST R Y OF THE DIGESTIVE PROCESSES.

From tMs variable material products showing mimite variations are
produced, of wliich we only know that they are more soluble than the
mother substance, less easily thrown out of solution by various precipit-
ants, and to a certain slight extent are capable of diffusing through
membranes.

Here our knowledge at present stops. In spite of most laborious
researches on the subject by a host of observers, we know no more of
the structure of any save the final decomposition products of proteid
digestion than we do of the proteids themselves. Certain products have
been isolated at various intervals in the progress of digestion of proteids,
which show that the process gives rise to several intermediate bodies,
ever increasing in solubility tow^ards precij)itants as they are formed
nearer the end of the process ; and it may be — it is a probable inference
from analogy — that these substances are simpler than the proteids from
which they originate, but as yet the sunplest of them is too complex
for our fragmentary knowledge to give any indication of its structure.
Nor is there any knowledge of the relationship of these several stages of
proteid digestion to one another.

It is very probable that the process of proteid digestion, Kke all the
other digestive processes, is one of continuous absorption of the elements of
water or hydrolysis.

This is shown by the following observations : — (1) One of the commonest
agents employed in organic chemistry for the purpose of hydrolysing a
substance is boiling with a dilute mineral acid, or subjecting in closed
vessels to the action of superheated steam. On submitting proteids to the
prolonged action of these reagents, products closely resembling or identical
with those produced by the action of the proteolytic enzymes are obtained.
(2) A small but decided increase in weight has been observed in the formation
of peptone from proteid.^ (3) Peptones can be converted artificially back
into proteids by the use of reagents which are essentially dehydrating in
their action. If fibrin-peptone be heated for an hour Avith acetic anhydride,
the excess of anydride distilled off along with acetic acid formed in the pro-
cess, and the residue treated with hot water, the greater part of it dissolves.
When this solution is dialysed, there remains behind in the dialyser a solution
which coagulates on boiling, and is precipitable by nitric acid or potassium
ferrocyanide. Also, peptone heated for some time to 140° C. yields a substance
which on solution in water shows more of the properties of a native albumin
than of a peptone.^

Other theories regarding the digestion of proteids are — (1) That the proteids
are polymers of the peptones, and that the process of digestion is a process of
depolymerisation,^ (2) that proteids and peptones are simply different isomeric
forms of the same substance, and (3) the micellar theory,* according to which
the proteids are composed of micelli, Avhich are a kind of second order of
molecule much more complex in structure. On peptonisation, the proteid first
breaks up into its constituent micelli, then the micelli fall into molecules, in
the chemical sense of the word, and these molecules are the peptone molecules.

^ A. Danilewslci, Centralbl.f. d. mccl. Wissensch., Berlin, 1880, No. 42, S. 769.

- Henninger, Compt. rend. Acad. d. sc, Paris, 1878, tome Ixxxvi. p. 1464; Hofmeister,
Ztschr. f. plvijsiol. Cham., Strassburg, 1878, Bd. ii. S. 206; Neumeister, Ztsclir. f. Biol.,
Mlinchen, 1887, Bd. xxiii. S. 394.

3 Maly, Arch. f. d. ges. Physiol., Bonn, 1874, Bd. ix. S. 585; ibid., 1879, Bd. xx.
vS. 315 ; Herth, Ztschr. f. physiol. GJiem., Strassburg, ]^)d. i. S. 277 ; Monatsh. f. Chem.,
Wien, Bd. v. ; Poelil, Bar. d. deutsch. chem. Gescllsch., Berlin, 1881, S. 1355; 1883, S.
1152; Loew, Arch. f. d. ges. Physiol., Bonn, 1883, Bd. xxxi. S. 393.

■* Griessniayer, Jahresb. ii. d. Fortschr. d. Thicr-Chcm., Wiesbaden, Bd. xiv. S. 26.



PEPTIC DIGESTION OF PR O TEIBS. 40 1

Ultimate chemical analysis shows that the composition of the peptones
and albumoses is practically the same as that of the proteids from which they
are formed ; in some cases the proteids show a somewhat higher percentage of
carbon and lower of hydrogen and oxygen than the proteids of their digestion,
in others the reverse, but in no cases any very considerable variation. So
that, if the process of peptonisation is one of hydrolysis, the peptone molecule
must be out of all proportion greater than that of the molecule of water.
^Nevertheless the hydrolytic theory is the one most generally received, and
against this unfavourable argument from analytical results must be set the
other experiments already quoted.

The main differences between the proteids and peptones of physio-
logical importance are the physical ones, that the latter are much more
soluble, and are diffusible, though with difficulty, through membranes.
It is indeed purely by physical means that we at present differentiate
proteids and peptones and the intermediate products between them,
and not by any well-marked chemical differences shown by them. The
different proteids, albumoses, and peptones are classified and marked
off from one another almost entirely by the behaviour of their solutions
towards solutions of neutral salts of different strength, according to
whether these dissolve or precipitate them. It is questionable whether
it is justifiable on such a slender basis to assume, as is commonly done
that these precipitates correspond to pure compounds. It ought to be
remembered that these names at present only apply to certain precipi-
tates, and that it is not at all known whether these represent distinct
chemical substances, nor indeed what they do represent. Still less right
have we to assume from mere proteid analyses that the products of
digestion of different proteids yield substances distinctive of them and
worthy of distinctive names.

The two proteolytic enzymes, pepsin and trypsin, closely resemble
each other in their action on proteids, a series of very similar products
being in each case evolved, which, generally speaking, become more
soluble and probably simpler in constitution as the end of the process is
approached. Still there is sufficient difference to warrant a separate
consideration of the two processes.

Peptic Digestion of Pkoteids.

The stomach was recognised even by the ancients as a digestive
organ, and its action attributed in many cases to the " animal heat "
assisted by mechanical force. Digestion seems to have been first con-
sidered as a similar process to fermentation by van Helmont, and this
view was also maintained by Sylvius.

Eeaumur^ seems to have been the first to experiment on gastric
digestion. He carried out his successful experiments on a tame buzzard,
which, like some other birds of prey, regurgitates after a time the more
indigestible portions of its food. He administered various kinds of
food, enclosed in small metallic tubes closed at one end and covered by
muslin at the other, so as to prevent any mechanical action of the
gizzard and yet allow the gastric juice to act ; he found that meat was
digested in the course of some hours, and in a shorter period was digested
partially on the outside while the interior still remained untouched.
Eeaumur also obtained gastric juice by enclosing pieces of sponge in
1 " Hist. Acad. roy. d. sc. de Paris," 1752, pp. 266, 461.
VOL. I. 26



402 CHEMISTR Y OF THE DIGESTIVE PROCESSES.

such tubes, but could not get it to act outside the body. Similar ex-
periments were carried out by Stevens ^ of Edinburgh, who availed him-
self of the services of a juggler possessing a trick of swallowing stones
and regurgitating them. This man he gave to swallow some hollow
silver balls which were perforated with holes ; the balls were screwed
together in two halves and could be filled with meat. He found that
the meat was rapidly dissolved and disappeared. To Stevens also belongs
the credit of being the first to observe digestion outside the body. He
obtained gastric juice from a dog's stomach, and found that when a piece
of meat was subjected to its action in a warm place it became dissolved
in about eight hours.

Soon afterwards Spallanzani confirmed these experiments, and
showed conclusively that, under favourable conditions, the juice acted
outside the body, and also that it had a marked action in preventing
putrefaction.

Between 1825 and 1833 Beaumont published his classical observa-
tions on Alexis St. Martin. In 1834, Eberle^ discovered a method of
preparing an artificial gastric juice, which possessed all the digestive
properties of the normal secretion, by acting on the gastric mucous
membrane with dilute hj^drochloric acid. Schwann^ in 1836 gave the
name pepsin to the active principle to which he supposed the gastric
juice owed its activity.

Products of peptic digestion. — The first exact investigations into
the nature of the products of gastric digestion are those of Meissner *
and his pupils. After digestion in acid solution and filtration, a pre-
cipitate was obtained on nearly neutralising, to which the name of
parapeijtone was given.

There is a considerable difference of opinion among various authors as to
what this parapeptone of Meissner is represented by in our more modern nomen-
clature. By some it is stated to have been syntonin. If Meissner had used a
strongly peptic digestive medium, filtered and neutralised, just after the bulk
of the proteid was dissolved, he would undoubtedly have obtained syntonin or
acid albumin ; but from his description it is evident that he was dealing
with a substance afterwards discovered by Klihne, and renamed antialbumate.
This substance seems by its behaviour to be indeed a close ally of acid
albumin, and is obtained most readily by a more prolonged action of dilute
acids at 40° C. than is necessary to form acid albumin. It is also formed to
a small extent in a loeak peptic digestive medium, probably from a similar
cause. Like acid (or alkah) albumin, it is insoluble in water, but easily
soluble in even very dilute acids or alkalies ; but it differs from acid albumin
in that when once formed it is not attacked by any pepsin in acid solution
by which acid albumin is actively peptonised. It is, however, convertible into
peptone (antipeptone) by the action of pancreatic juice, no leucine or tyrosine
being simultaneously formed. Meissner was undoubtedly using very weak
solutions of pepsin, and the action he obtained approximated to the prolonged
action of weak acids alone at 40° C. The action of the pepsin present was
too weak to catch, as it were, all the acid albumin on its way into antialbumate
and peptonise it ; and when once any antialbumate was formed, it could not then
be attacked and peptonised. Meissner's product Avas thus almost purely anti-

■^ " De alhnentorum concoetione," Edin., 1777.

^ "Physiol, d. Verdauimg iiach Versuch.," Wiirzburi,', 1834.

^ Arch. f. A licit., Physiol, u. wissensch. Med., 1836, S. 90.

^ Ztschr. f. rat. Med., 1859-1862, Dritte Reilie, Bd. vii. ,S. 1 ; viii. S. 280 ; x. S. 1 ;
xii. S. 46 ; xiv. S. 303. Reviewed in Biol. Centralbl., Erlangen, 1884, Bd. iv. S,
407.



PR on UCTS OF PEPTIC DIGESTION. 403

albumate. If he had used a slightly stronger solution for a somewhat shorter
time, he Avould have obtained a mixture which would have been partially
peptonised and partially remained unchanged when subjected to the action
afterwards of strong fresh pepsin and acid ; if he had used a strongly peptic
solution for a much shorter time, the result would have been purely acid
albumin and no antialbumate whatever ; giving with fresh pepsin, or more
prolonged action, complete peptonisation.

On the addition of acid to the almost nQwivdl faintly acid solution, a
further precipitate formed, which Meissner regarded as a different sub-
stance, and called metcqjeiJtone. It was insoluble in very dilute acids (O'l
per cent.), soluble in stronger acids. A third residue obtained in the diges-
tion of casein or fibrin he called dyspeptone ; this was insoluble in dilute
acids (2 per cent. HCl), but soluble in dilute alkalies and in stronger
acids. This substance was probably a mixture of nucleins, with the sub-
stance subsequently described by Klihne as antialbumid.^

After the removal of these neutralisation products, various other
substances were still left in solution ; these Meissner classed together
as peptones, distinguishing —

a-peptone, precipitable by concentrated nitric acid, as well as by potassium
ferrocyanide and dilute acetic acid.

/3-peptone, not precipitated by nitric acid, but by potassium ferrocyanide
and strong acetic acid.

y-peptone, not precipitated either by nitric acid or by potassium ferro-
cyanide and acetic acid.

Of these three substances only y-peptone corresponds to the present-day
definition of a peptone ; the others were probably different albumoses.

A valuable side-light was thrown on the digestion products of
proteids by Schiitzenberger's ^ researches on the prolonged action of
acids and alkalies at liigh temperatures on these substances. It has
already been indicated that peptonisation is the result obtained,
followed finally by a splitting up into amido-acids.

Superheated steam possesses a similar peptonising action on proteids, and
yields by prolonged action the usual amido-acids. ^ According to ISTeumeister,*
the intermediate substances produced are, however, somewhat different, the
substance first formed lies intermediate between the coagulable proteids and
the albumoses. It is not coagulated by boiling, but in its behaviour towards the
usual precipitants behaves like a coagulable proteid ; this substance is termed
atmidalbumin. By further hydration it yields a true albumose, which, however,
differs somewhat in its properties from any of the albumoses naturally formed
in digestion, and has been named atmidalbumose. Both atmidalbumin and
atmidalbumose are precipitated by dilute acids, and are converted by boiling
with dilute sulphuric acid into deutero-albumose. Similar products are pro-
duced by the action of the vegetable digestive ferment papoyotin or papain,
and are in the end, by the prolonged action of this ferment, converted into
amido-acids.^

1 See p. 406.

^ Bull. Soc. cJiion.., Paris, 1875, tome xxiii. pp. 161, 193, 216, 242, 385, 433 ; xxiv. pp.
2, 145 ; Jahrcsb. ii. d. Fortschr. d. Thier-Chem., Wiesbaden, 1875, Bd. v. S. 299.
Schutzenberger's researches are referred to at length in the article on the " Chemical Con-
stituents of the Body," pp. 30-32 of this volume.

^ Lubavin, Hoppc-Seylei's Mcd.-cliem. Untersicch., Berlin, 1871, S. 480; Krukenberg,
Sitzungsh. d. Jenaisch. Gesellsch. f. Med. ii. Naiiorw., 1886.

^ Ztschr.f. Biol. Mtinchen, 1890, Bd. xxvi. S. 57.

^ Sidney Martin, Journ. Physiol., Cambridge and London, 1885, vol. vi. p. 336.



404 CHEMISTR Y OF THE DIGESTIVE PROCESSES.

Meissner's views as to the decomposition of proteids ou digestion
did not at first obtain much credence. The formation of a sulDstance
precipitated by neutrahsation, and incapctble of furtlur conversion hy
'pepsin and an acid in the course of normal digestion, was denied, and
with right, by Brlicke and others.

Brlicke^ stated that there was no such decomposition of tlie pro-
teid molecule as Meissner indicated, but that fibrin is first dissolved
and afterwards converted in great part into acid albumin, accom-
panied even at first by peptone in small quantity. If neutralisation
takes place at this stage, a heavy precipitation is the result, and there
remains in solution a small quantity of coagulable proteid (formed by
the solution of the fibrin and not yet converted into acid albumin by
the acid) mixed with albumoses and peptone. If, however, peptic
digestion be allowed to proceed to completion, no precipitation occurs
on neutralising, and the solution contains only albumoses and peptones.
This shows that Meissner's parapeptone, as well as Kiihne's antialbumate
and antialbumid, which will be described later,^ are not formed to any
extent in active peptic digestion, but are merely products of prolonged
action of dilute acid.

In order to study the products formed in peptic digestion, it is necessary
to proceed with a digestive fliud which has been purified from products of
digestion, due to self-digestion or otherwise, by one of the methods aheady
described,^ or else to take advantage of a peculiar property possessed by
fibrin, and in a lesser degree by some other forms of proteid, of absorbing
pepsin from sohition.*

Any digestive fluid containing pepsin (such as that obtained by auto-
digestion of pig's gastric mucous membrane in dihite hydrochloric acid) is
carefully neutralised, using powdered chalk for the purpose, so as to avoid all
danger of alkalinity, by Avhich the pepsin would be rapidly destroyed.^ After
neutralising and filtering, the fluid is shaken up with flakes of fibrin for
some time ; this is best done by blowing a stream of air through the mixture,
placed in a tall vessel, by means of a Bunsen filter pump. In about an hour
the fibrin becomes impregnated with pepsin, which, however, cannot attack it
in the neutral fluid. So firmly adherent is the enzyme to the fibrin, that the
latter may be freely washed without parting from it. If this fibrin be now
placed in dilute hydrochloric acid ('2 per cent.) at 40° C, it is quickly dis-
solved and digested. Instead of neutralising the impure digestive fluid, it
may be saturated with sodium chloride, which stops the digestive action of the
pepsin ; on now agitating thoroughly for about an hour, the fibrin is saturated
with pepsin, after which it may be washed as before. This peculiar power of
absorbing pepsin is shown in a varying degree by all solid forms of proteid.
Fibrin possesses it most markedly, muscle fibre and casein also show it well,
but coagulated proteids show it comparativel}^ much more feebly.*^

Fibrin, or other solid proteid, on digestion, swells up, dissolves, and
is converted into syntonin or acid albumin. The same result is obtained

1 Sitzungsb. d. Jc. Akad. d. Wissmsch., Wien, 1859, Bd. xxxvii. S. 131 ; 1861, Bd. xliii,
S. 601.

2 See pp. 406-409. 2 gg^ p_ 492.

■*Von Wittich, Arch. f. d. ges. Physiol., Bonn, 1872, Bd. v. S. 443 ; K. Mann, "Ueber
die Absorption der proteolytischen Enzyme durcli die Eiweisskorper," Inang. Diss.,
Wiirzburg, 1892, S. 23.

° Langley, Journ. Physiol., Cambridge and London, 1882, vol. iii. p. 253.

^ Wurtz, Compt. rend. Acad. d. sc, Paris, 188i, tome xciii. p. 1104; A. Fick,
Sitzungsb. d. phys.-med, Gesellsch. zu Wiirzburg, 1889, S. 23; K. Mann, Inaug. Diss.,
Wurzburg, 1892.



CLE A VA GE THE OR Y OF PRO TEW DIGESTION. 40 5

with acid alone, but incomparably more slowly. The acid and ferment
seem to mutually assist each other. Pepsin alone is inactive, the acid
alone acts with extreme slowness, but in the presence of the acid the
ferment speedily dissolves the proteid, which is then rapidly attacked by
the acid and converted into acid albumin.

When the proteid undergoing digestion is fresh fibrin which has not been
previously subjected to heat coagulation, a body possessing the properties of
a globuhn is found in the sohition in the first stage of digestion, before or
just when complete solution has taken place ; a similar body is also said to be
formed in small quantity as a first product of digestion of other forms of
proteid. 1 In a recent paper it is stated by Arthus and Huber- that this
globulin is simply dissolved fibrin. These authors found such a body co-
agulating at 56° C. on digesting unboiled fibrin ; but boiled fibrin yielded no
such product. They also determined that " Witte's Peptone " dissolved un-
boiled fibrin, at 40° C, giving a solution which coagulated on heating at
56=, 68°, and 75° C.

The acid albumin is next attacked by the pepsin and further
altered, giving rise to a number of substances called alhumoses, j^roteoses,
or proiJeptones, and these in turn are slowly and incompletely con-
verted into peptones. Here the action of pepsin ceases.

Cleavage theory of proteid digestion.— The cleavage theory of
proteid digestion was first enunciated by Klihne in 1877.^ He describes
the digestion of albumins by trypsin as taking place in two stages : in
the first stage the albumin is changed into peptone (amphopeptone) ;
in the second stage, one-half of this peptone (hemipeptone) is further
changed, while the other half (antipeptone) remains unaltered. Peptic
digestion is not essentially different from the first stage of tryptic, and
while it is not possible to obtain two bodies from pepsin peptone, still it
is probable that this substance is a mixture of two bodies, antipeptone
and hemipeptone, as is also the case after the first stage of tryptic
digestion.

Unable to isolate two bodies from the end products of peptic
digestion, one of which should remain unchanged when subjected to
tryptic digestion, while the other broke up under like treatment into
leucine and tyrosine, Kiihne surmised that the cleavage might take
place earlier in the process of peptic digestion, and that more success
might attend an attempt to separate the precursors of anti- and hemi-
peptone, namely, the corresponding albumoses, by interrupting peptic
digestion at an early stage, and experimenting upon the products then
in solution. By interrupting peptic digestion at an early stage, two
substances were obtained : one was a neutralisation precipitate, which, on
tryptic digestion, afterwards yielded only antipeptone, and was hence
named antialhumose ; the other, obtained from the filtrate, was de-
composed by trypsin, with formation of leucine and tryosine, and was
hence named hemicdbumose.^ Kiihne ^ also reinvestigated the action of
acids, renaming Schtitzenberger's hemiprotein antiatbumicl, and a body

1 Brlicke, Sitxungsb. d. k. Akad. d. Wissenscli. , Wien, 1859, Bd. xxxvii. S. 182 ; Otto,



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