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work, metabolising at the same time a very considerable amount of
proteid, the oxidation of which could have been the only source of the
greater part of the energy. Whether, however, as Pfiiiger holds, the
living tissue i^refa^s to emiAoy proteid, when it has sufficient offered to it,
for the production of work, or whether, as is generally supposed, it
uses up first the available non-proteid material for the production of
energy, and only secondarily calls upon the proteid for the purpose of
oxidation and energy production, is a matter which it is not at all easy
to settle. That proteids enter largely into the diet of athletes is a
fact which is of some importance in connection with the question.
But although for short periods athletes are unquestionably capable of
doing a very large amount of work, it must be remembered that their
diet is by no means rigidly confined to proteid substances. It must
also be borne in mind that there is a large class of labourers both in
this, but more especially in other countries, who get through a much
larger average amount of work per diem than is performed by athletes,
and who, nevertheless, frequently have an amount of proteid in their diet
the oxidation of which is altogether insufficient to account for the work
done. Tlie fact that a proteid diet has been selected for training purposes
may be due, in the first place, to the more ready assimilation of proteid by
the body ; and, in the second place, to the fact that it is specially required
in these cases, because during training it is important to encourage the
building up of muscular tissue, and for this purpose proteid is necessary ;
not because the proteid of the diet is itself more readily oxidised and
converted into energy by oxidation than the non-proteid materials.

But whether there may be produced under some circumstances as
the result of muscular exercise an increase in the nitrogen of the egesta,
it is certain that the most prominent effect upon the egesta of activity
of the muscles is an increase in the amount of carbon dioxide,^ such
increase being either unaccompanied by, or altogether disproportionate
to, any rise in the nitrogen egested. It must therefore arise from the
oxidation of non-nitrogenous materials, i.e. fat and carbohydrates.

CI. Bernard was of opinion that the grape-sugar which he had dis-
covered in the liver and in the blood might by its oxidation in the
tissues take an important part in the production both of heat and of
mechanical energy. Seegen^ is disposed to go much further than
this, holding that muscular energy is obtained solely from the oxidation
of dextrose brought to the muscles by the blood. He finds, as others
have done, that sugar is never absent from the blood even after pro-
longed fasting, and that there is an excess of glucose in the hepatic
blood, independent of the presence or absence of glycogen in the liver.
He also finds in most cases a diminution in the percentage amount of
sugar in the venous blood leaving a muscle, as compared with that in
arterial blood. Some of Seegen's results are, however, paradoxical,
nor have they received adequate confirmation, although a similar

^ Cf. article " Chemistry of Respiration."

^ " Die Zuckerliilduiig im Thierkorper," Berlin, 1890 ; and Arcli.f. d. ges. Physiol. , Bonn,
189], Bd. 1., which volume also contains a criticism of Seegen's views by Pfiiiger. See also
on this subject I. Munk, Verliandl. d. jjhysiol. Gesdlsch. c?( Berlin, in the Arch. f. Physiol.,
Leipzig, 1896, S. 372 ; Zuntz, ibid., S. 538, and Centralhl. f. Physiol., Leipzig n. Wien, 1896,
S. .'jei ; and Mosse, Arch.f. d. ges. Physiol., Bonn, 1896, Bd. Ixiii. S. 613. Other papers by
Seegen relating to this subject will be i'ound in the Centralhl. f. Physiol., Leipzig u. Wien,
during the last few years, and in the Arch. f. Physiol., Leipzig, 1895 and 1896.


difference in the amount of sugar of the blood passing to and from an
active muscle has been obtained by Chauveau and Kauf mann ; ^ such
differences as are found generally fall within the limits of experimental
error. Chauveau ^ has further endeavoured to show that in dogs
muscular work is not effected at all at the expense either of the
proteids of the body or of the food ; but, as I. Munk has pointed
out, the results obtained cannot be accepted as conclusive.^ That
glycogen disappears both from the liver and from the muscles of
dogs, and from the " surviving " excised muscles of the frog, con-
comitantly with the production of muscular work,* is held to be an
argument in favour of this work being done at the expense of this
carbohydrate. Under certain circumstances, however, the glycogen of
the muscles may be caused to entirely disappear, although they are still
capable of performing a large amount of work, which must, under
these circumstances, be otherwise derived, however probable it may
be that under normal circumstances the oxidation of dextrose or
glycogen plays an important part in its production.

In support of the view that muscular energy may be largely derived
from the oxidation of carbohydrate materials, it has been observed by
Tiegel,^ that the Japanese rickshaw runners consume rice in large
quantities, and at frequent intervals, during their periods of work,
whereas on off-days they live mainly on a llesh diet.^

Pfliiger " kept a dog of 30 kilos, weight in equilibrium upon perfectly lean
meat, containing a very large preponderance of proteids over non-proteids.
When caused to pass from a condition of rest to hard work, it lost flesh if kept
on the same diet, imtil it assumed a lower position of N-equilibrium, but main-
tained or even added to its weight if the amount of flesh was increased 500
grms. per diem ; about 50 per cent, of the potential energy of the additional
proteid appearing as work. If now, whilst in N-equihbrium on lean flesh, fat
and carbohydrate were added to the diet, these were not utilised for the pro-
duction of energy, but were stored as fat ; hence, Pfliiger argues, the living
tissue prefers to use the proteid, and only takes non-proteid if insufficient proteid
is off"ered to it. It should, however, be pointed out that Pfliiger's dog was,
with its purely proteid diet, in a condition of extreme emaciation,^ and the cir-

^ Compt. rend. Acad. d. sc, Paris, 1887, tome civ. pp. 1126, 1352, and 1409. Similar
results (disappearance of sugar from blood passing through active muscles) have been
obtained by Morat and Dufourt {Arch, de physiol. norm, et 2Mth., Paris, 1892, p. 327), who
also found a certain disappearance after the work, which they suppose due to glycogen stored.

- With Contejean, Compt. rend. Acad. d. sc, Paris, tome cxxii. pp. 429, 504.

' Verhandl. d. physiol. Gesellsch. zu Berlin, 8 Mai, m Arch. f. Physiol., Leipzig, 1896.

■* 0. Nasse, Arch.f. d. ges. Physiol., Bonn, 1869, Bd. ii. S. 97 ; also Weiss, Sitzungsh. d. k.
ATcad. d. Wisscnsch., Wien, 1876, Bd. Ixiv. S. 288 ; Marcuse, Arch. f. d. ges. Physiol.,
Bonn, 1886, Bd. xxxix. S. 425; Manche, Ztschr. f. Biol., Miinchen, 1889, S. Bd. xxv.
164 ; and ibid., 1877, Bd. xiv. S. 473.

5 Ibid., 1883, Bd. xxxi. S. 607.

^ U. Mosso and Paoletti {Atti d. Accad. d. Lincei, Eoma, 1893) and V. Harley
[Proc. Boy. Sac. London, 1893, p. 480, and Journ. Physiol., Cambridge and London, 1894,
vol. XV. p. 97) using the ergograph of A. Mosso, found that they could perform a greater
amount of voluntary muscular work when a large amount of cane-sugar was added to the
diet. Experiments of this nature are, however, liable to a psychical error, and, as a
matter of fact, experiments by Langemeyer (with Stokvis) made upon different persons
failed to give similar results (see discussion in Brit. Med. Journ., London, 1895, vol. ii.
pp. 1280-1285).

' Arch.f. d. ges. Physiol., Bonn, 1891, Bd. 1. S. 98, and Bd. Ii. S. 317.

* It may be noted in this connection that the " Banting cure " for obesity depends upon
the principle of selecting a diet not necessarily insufficient, but consisting mainly of lean
meat. As in the case of Pfliiger's dog, the tissues under these conditions use up the body-
fat, which thus becomes gradually reduced in amount.


cumstance of the fat and liver cells seizing upon non-proteid materials and storing
them as fat and glycogen in an animal in this condition, is not surprising,
and is quite compatible with the view that in a normally nourished animal,
where they are in excess, the non-proteids are the main energy producers.

The most probable view appears to be that muscle, like other cells,
although it can only actually build up its bioplasm out of proteid, is
nevertheless able to produce muscular energy by oxidation — perhaps
occurring outside the actual molecules of the bioplasm, but under their
direct influence — of any or all the organic foodstuffs,^ and that this
process is attended only by such small disintegration and loss of the
proteid material of the bioplasm as is necessarily attendant upon its
functional activity — a loss which is comparable to the wear and tear of
the working parts of a machine as distinct from its consumption of fuel.

As a matter of fact, it has been shown by Zuntz,^ that in a dog,
abundantly fed on a mixed diet and caused to produce external work,
the amount of extra proteid used during the period of work was less
than one-twentieth part of the amount the oxidation of which would
have been necessary to account for the work done. Moreover, in in-
anition it is the glycogen and fat of the body which is first drawn upon,
and this both at rest and during work. When the same dog was made
to work during fasting, the JST-secretion rose only very slowly ; the
work was almost entirely done on the non-proteids of the body.

It may be remarked that muscular activity is always accompanied
bj a production of energy far in excess of that which is necessary for
the performance of the external work done. Thus it was found by
Hanriot and Eichet ^ that when work was done there was seven times
as much COg produced as would have been accounted for by the oxida-
tion necessary to perform the work. The additional energy appears of
course as heat. On the other hand, it has been doubted whether there
is any production of heat in the total absence of muscular activity.*

Hanriot and Richet found the CO., to increase in greater proportion than
the oxygen absorbed, so that the respiratory quotient became larger. Severe
muscular exercise is stated to increase both the phosphoric acid ^ and the
sulphur of the urine ; '° the former more in proportion than the increase of IS^
which may occur ; the latter about in proportion to the increased IS^, and in
the form of ordinary sulphates." Along Avith the increase of phosphoric acid,
there is also an increased excretion of lime, indicating, according to I. Munk,
destruction of bony tissue.

Metabolism of Carbohydeate.

The formation of glycogen. — The carbohydrates of the food are
mainly converted by digestion into maltose, which passes in the process
of absorption and assimilation into dextrose, tliis being the only sugar

^ Of. Noel Paton, Eclin. Med. Journ., June 1895. A\so Rep. Lab. Roy. Coll. Phys.,
Edin., 1891, vol. iii.

2 With Freiitzel and Loeb, Arch. f. Physiol., Leipzig, 1894, S. 541 {Vcrhandl. d.
lihysiol. Gesellsch. zu Berlin). See also Speck, ibid., 1895, S. 465.

^ "Tiavaux du laboratoive de Ch. Richet," 1893, tome i.

■* Cf. on this subject Speck, Ceniralbl. f. d. vied. Wissensch. , Berlin, 1889 ; also article
"Animal Heat," p. 840.

s King and Olsavsky, Arch. f. d. ges. Physiol., Bonn, 1893, Bd. liv. S. 21.

® Beck and Benedikt, ibid., S. 27.

' L Munk, VerhamU. d. 2^hysiol. Gesellsch. zu Berlin, 5th April 1895 (in Arch. f.
Physiol., Leipzig).


which is unmistakably found in the circulating fluids and in the tissues
of the body. The path of absorption of carbohydrates is the same as
that of proteids/ the absorbed dextrose being taken up by the blood,
conveyed by the portal vein to the liver, and there stored. The portal
blood taken during digestion is, in fact, the only blood in the body in
which it can be conclusively shown that normally there is an excess
of sugar. If taken in the intervals of digestion, it contains the same
amount of sugar (one to two parts per thousand) as any other sample
of blood.

The blood of the hepatic vein, on the other hand, although it is said
to contain an excess of sugar in the intervals of absorption of foods
containing carbohydrates (but mde infra, p. 923), does not, during the
actual process of such absorption, contain nearly as much sugar as the
blood of the portal vein ; we must therefore assume that the sugar
which is carried to the liver by the portal vein is arrested in that
organ. As a matter of fact, it is found that the immediate result of
the digestion and absorption of a meal containing much carbohydrate
food is to promote a considerable accumulation of glycogen in the liver,
and the same is found if in a fasting animal solution of dextrose is
slowly injected into a vein of the mesentery,^ or if dextrose is injected
subcutaneously (in rabbits).^ The same is even found if blood contain-
ing dextrose is perfused through the " surviving " liver of a dog."^ The
amount of glycogen in the liver (which would contain in man at most
150 grms. of this substance) ^ is not sufficient to account for the storage
of the whole of the carbohydrate which is absorbed from a meal con-
taining much starch or sugar. A part of the absorbed carbohydrate,
when it is in excess, must therefore pass through the liver into the
general circulation. Here it is apparently taken up by the muscles, for
in a well-nourished animal, especially one nourished upon mixed food,
the muscles may contain as much as 1 per cent, or even more of
glycogen. Although this is not by any means as large a proportion as
may be contained in the liver itself,^ the muscles may collectively hold
as much as is present in the liver.'^ Even, however, if we take into
consideration the whole of the glycogen in the liver, that in the muscles,
and that in other tissues in the body in which it might be stored, it will
still be found that the whole of the carbohydrates of a meal which
contains much of these substances is not represented in the body,
either by the glycogen of the organs or by the sugar present in the

1 See this Text-book, vol. i. pp. 432-436.

^Bernard, " Lecons de physiol. exper.," Paris, 1855.

3 G. Lusk (with'Voit), Ztschr.f. Biol., Miinchen, 1892, S. 288. The ingestion or sub-
cutaneous injection of Isevulose will also cause a production of glycogen ; galactose and
lactose do not (C. Voit, Ztschr.f. Biol. , Miinchen, 1 892, Bd. xxviii. S. 245). Kausch and Solin
{Arch. f. exper. Path. u. PharmakoL, Leipzig, 1893, Bd. xxxi. S. 398) obtained positive
results with lactose and galactose. Cf. also Crenier, ihid., 1893, Bd. xxix. S. 484 ; Haycraft,
Ztschr. f. physiol. Chem., Strassburg, 1894, Bd. xix. S. 141. Whether the leevulose is first
converted into dextrose, and this into glycogen, or whether the glycogen is formed directly
from Ifevulose, the ketone group of Ijevulose must in either case become converted into an
aldehyde group (Neumeister, "Lehrbuch," Aufl. 2, S. 3-26). On the subject of the forma-
tion of glycogen from carbohydrates, see further, E. Voit, Ztschr.f. Biol., Miinchen, 1889,
Bd. XXV. S. 551 ; C. Voit, ibid., 1892, Bd. xxviii.

■^ Luchsinger, Inaug. Diss., Zurich, 1875.

^ Bunge, "Lectures," p. 383.

^ Pavy found in rabbits and dogs fed with a large amount of carbohydrate-containing
food, that the amount of glycogen of the liver might rise as high as 17 per cent. (" Physio-
logy of Carbohydrates," p. 116).

■^ Bohm, Arch.f. d. ges. Physiol., Bonn, 1880, Bd. xxiii. S. 51,


circulating fluid. The amount wMch is not accounted for may possibly
pass into the constitution of the proteids and nucleo-proteids, and also
of those albuminoids from which a carbohydrate material has been
obtained on decomposition with acids, and it may be that the excess is
in this way stored until required. In the embryo, glycogen is much
more widely distributed and occurs in much larger proportion than
after birth, especially in the developing muscles ; at this time the liver
may contain very little. It occurs also in considerable amount in the

The glycogen, both of the liver and of the muscles, gradually dis-
appears in starvation, and first from the Hver.^ The disappearance is
accelerated by muscular work,^ and in warm-blooded animals by external
cold ; ^ it is probable, therefore, that the glycogen is used for the pro-
duction of both work and heat. The rate at which it disappears in
starvation varies greatly in different animals. Aldehoff found it in large
quantity in the muscles of a horse which had fasted for nine days ;
in dogs it may be found after three weeks, and has been detected
after thirty-five days' fasting ; * in rabbits it has disappeared usually
within a week. In frogs it accumulates in the liver tow^ards the
end of the summer, and gradually disappears during the winter;
but even if they take no food, there is still some present at the end
of the winter, but more in the muscles than in the liver. The same
is the case with hibernating animals (Voit). On the other hand, if
carbohydrates are given to animals deprived of their glycogen by
starvation, this substance very rapidly reappears in the muscles and

The diminution of the glycogen of the muscles, concomitantly with their
activity, has been already referred to in connection with muscular metabohsm
(p. 915). In the passage of excised muscles into the condition of rigor mortis
there is a certain amount of disappearance, amounting, according to Werther,^
to as much as 50 per cent, of the original amount, hut far less than as the
result of tetanising the muscles. In either case, what becomes of it is not
clear ; the sarcolactic acid which makes its appearance is not derived from it ;
the formation of the acid is not dependent upon the presence or absence of
glycogen. If rigor is allowed to come on in the cold, the acid still appears, hut
there is no appreciable disappearance of glycogen.'^ On cutting the nerve pro-
ceeding to a muscle, the glycogen becomes increased in quantity.^ The increase
proceeds up to the fourth day. Section of the tendon of a muscle has a
similar effect.^

According to the observations of Kiilz, glycogen begins to appear in the liver

1 Aldehoff, Ztsclir. f. Biol., Munclien, 1889, Bd. xxv. S. 137 ; Hergenhalin, ihid., 1890,
Bd. xxvi. S. 225.

2 Maiiche, Ztsclir. /. Biol., Munehen, 1889, Bd. xxv. S. 163. The glycogen of muscles
disappears after a period of tetanus, and also in frogs poisoned by strychnia, but not in
the muscles of a leg the sciatic nerve of which has previously been cut.

" Kulz, Arch. f. d. ges. Physiol., Bonn, 1881, Bd. xxiv. S. 46. In cold-blooded animals
external ivannth produces the disappearance of glycogen from the liver (Langley).

•* Quinquand, Go'iivpt. rend. Soc. de biol., Paris, 1886, p. 285.

^ For references, see Bun ge, "Lectures," pp. 383-385. See also Langley, Pj^oc. Roy.
Soc. Lo^ndon, 1882, vol. xxxiv. p. 22 (histological observations) ; Quinquand, Comi^t, rend.
Soc. de biol., Paris, 1889, p. 285 ; Dewey re, ibid., 1892, No. 19.

** Arch.f. d. ges. Physiol., Bonn, 1890, Bd. xlvi. S, 63.

■^ Bcihni, ibid., 1880, Bd. xxiii. S. 44.

* Bernard, Compt. rend. Acad. d. sc, Paris, 1859, tome xlviii. p. 683.

^ Boldt, Diss., Wiirzburg, 1893; Vay, Arch. f. expcr. Path. u. Pharmalcol., Leipzig,
1894, Bd. xxxiv. S. 45.


of starved rabbits two to four hours after a meal containing carbohydrates, and
disappears after five to eight hours' hard muscular work (dog). It is formed
in the muscles of a frog which has been deprived of its liver ;i and may be
increased in muscular tissue by perfusing blood, to which grape-sugar has been
added, through the vessels of the muscle.-

The formation of glycogen from other than carbohydrate material.

— That glycogen can be formed in the entire absence of carbohydrate
material from the food, is shown by the fact that animals which have
been for a long time fed on lean meat, deprived as much as possible of
carbohydrate, are found to have even considerable amounts of glycogen
in their liver and muscles. Indeed, if an animal be allowed to fast
for some days, and to perform also severe muscular work, — circum-
stances under wdiich practically the whole of the glycogen can be made
to disappear both from the liver and muscles, — on now administering
proteid^ or gelatin* food, altogether free from carbohydrates, glycogen
will reappear both in the liver and in the muscles. Even without the
administration of food, by the employment of narcotic drugs, such as
chloral, which tend to diminish or arrest muscular activity, glycogen
will reappear ; ^ in this case it must be formed from the proteids of the
body. The administration of fat without proteid does not cause such
reappearance, nor does the addition of fat to the food, even in consider-
able excess, increase the amount of glycogen in the liver.^ Arsenic
poisoning causes a diminution in the glycogen both of the liver and of
the muscles ; probably by impairing the vitality of their bioplasm. On the
other hand, the administration of glycerin promotes the storage of gly-
cogen in the liver \'^ it acts, however, apparently rather by preventing the
removal of the glycogen, than by becoming itself converted into that
substance, or than by its becoming itself oxidized and thus acting as a
glycogen sparer (Eansom). Thus it is found that with glycerin adminis-
tration the sugar puncture is not able to produce glycosuria.

The administration of ammonium carbonate was also found by Rohmann ^
to promote the accumulation of glycogen in the liver, and this property is
shared by many ammonium compounds,^ but how they may act has not as yet

^ Ktilz, Arch. f. d. ges. Physiol., Bonn, 1881, Bd. xxiv. S. 64. This volume contains
several other papers by Kltk on the conditions of formation of glycogen.

- Kiilz, Ztschr. f. Biol., Miinchen, 1891, Bd. xxvii. S. 237 : there was, however,
only an increase in three out of eleven experiments.

^ Naunyn, Arch. f. expcr. Path. u. Pharmakol., Leipzig, 187.5, Bd. iii. S. 94 ; v.
Mering, Arch. f. d. ges. Physiol., Bonn, 1876, Bd. xiv. S. 281 ; KUlz, Funfzigj. DocL-
Juhelf. d. . . . Carl Ludwig, Marburg, 1890.

* Salomon, Virchoiv's Archiv, 1874, Bd. Ixi. S. 352 ; Luchsinger, Inaug. Diss., Zurich,
1875 ; V. Mering, loc. cit.

^ Zuntz u. Vogelius {Arch. f. Physiol., Leipzig, 1893, S. 378, Verhandl. d. physiol.
Gesellsch. zv, Berlin) obtained a reappearance of glycogen on administering chloral to
starved and strychnised rabbits.

® Chauveau has come to the conclusion that carbohydrate may be formed from fat in
the animal body {Comi^t. rend. Acad. d. sc, Paris, 1887, tome exxii. p. 1098), and Seegen,
" Die Zuckerbildung," also holds this view, but the evidence in its favour appears to be very

'' Weiss, Sitzungsh. d. k. Ahad. d. Wissensch., Wien, 1873, Bd. Ixvii. S. 13 ; Eckhard,
loc. cit. ; Luchsinger, Inaug. Diss., Zurich, 1875 ; W. Ransom, Journ. Physiol., Cambridge
and London, 1887, vol. viii. p. 99 ; Schenck, Arch. f. d. ges. Physiol, Bonn, 1894, Bd.
Ivii. S. 569.

^ Arch. f. d. ges. Physiol., Bonn, 1886, Bd. xxxix. S. 21. Cf. also Kiilz {Funfzigj.
Doct.-Jubelf. d. . . . Carl Ludwig, Marburg, 1890), who found that urea as well as
ammonia salts increased the glycogen of the liver.

9 Nebelthau, Ztschr. f. Biol., Miinchen, 1892, Bd. xxviii. S. 138.



been determined. Bicarbonate of soda is stated by Dufonrt to bave tbe effect
of increasing tbe amount of glycogen in the liver. Duf ourt's experiments
were made upon dogs on a flesb diet after a period of fasting.^

Grlycogen becomes formed in the embryo chick in considerable
amount, although there is very little glycogen or carbohydrate at all
in the egg. Here also it must in all probability be formed from proteid.
Grlycogen can only be supposed to be produced from proteids in the
animal body by a process of synthesis, preceded by a breaking down of
the proteid molecule.^ It is highly probable that dextrose is a stage in
the com'se of such synthesis ; and since dextrose is constantly found in
the blood, even in prolonged inanition, it may well be inquired wdiether
the carbohydrate of the body is invariably converted into glycogen,
prior to being employed by the tissues for the ]3roduction of energy.

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 128 of 147)