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and all the phosphorus of the original colloid.

The suprarenal body. — In this gland, in addition to proteids and
the usual extractives and salts (among which potassium phosphate is
the most abundant), various other substances have been described, such
as hippuric and tam^ochohc acid,^ benzoic acid, tamine,* and inosite.^

The chemistry of the suprarenal is of especial interest because of the
work of Schafer and Ohver^ on the action of extracts obtained from
it. It is now generally beheved that the fmiction of the gland is
secretory, and that the fatal effects of its removal in animals, or
disease in man (Addison's disease), is due to the removal of an internal
secretion, and not to auto-intoxication from the non-removal of waste
products.'' The active principle is obtained from extracts of the
medulla of the healthy gland ; it is absent in advanced cases of Addi-
son's disease.

The earlier observers^ were inchned to attribute the toxic
results of suprarenal injections to neurine. This is not so. Nemine

^ Ztschr. f. Biol., Miinclien, 1896, Bd. xxxiii. S. S3 ; Centralhl. f. Physiol., Leipzig,
Bd. ix. S. 704.

'^ Brit. Med. Journ., London, 1896, vol. i. p. 722; 1897, vol. i. p. 4; Journ. Physiol.,
Cambridge and London, 1896, vol. xx. p. 474.

•* Cloez and Vulpian, Gompt. rend. Acad. d. sc, Paris, 18f)7, tome ii. p. 10 ; Gaz. mid.
de Paris, 1858, No. 24.

■* Seligsohn, Diss., Berlin, 1858; Holm, Journ. f. praM. Clicm., Leipzig, Bd. c. S. 150.
Stadelmann could not confirm these statements, Ztschr. f. physiol. Chem., Strassburg, Bd.
xviii. Possibly these substances are absorbed from the neighbouring gall bladder and

' Klilz, Sitzungsb. d. Gesellsch. z. Bef'ord. d. ges. Naturw. zn Marburg, 1876, No. 4.

® Journ. Physiol., Cambridge and London, 1895, vol. xviii. p. 230. Some speculations
as to the function of the cortex by Auld will be found, Brit. Med. Journ., London, July
4, 1896 ; Manasse, Virchow's Archiv, Bd. cxxxv. S. 263.

'' The discovery of hferaochromogen in the medulla of the organ by j\LacMunn {Proc. Boy.
Soc. London, Bd. xxxix. S. 248) appeared to favour the removal hypothesis.

* Pellacani, Arch, j'ler le sc. m-ed., Torino, 1874, vol. iii. ; Foa, ibi<l., 1884, vol. viii. ;
Marino-Zucco, Gliem. Centr.-BI., Leijjzig, 1888; Untersuch. .;-. Naturl. d. Mensch. u. d.
Thier, Bd. xiv. ; Arch. ital. de biol., Turin, vol. x.



can be obtained from the gland, it is true, but the symptoms
of neurihe poisoning are different. The active principle has not
yet been satisfactorily identified, although its soluljilities and many
of its reactions have been worked out by Moore,^ who at first thought
it identical with a powerfully reducing substance found only in the
medulla of the gland, and first described by Vulpian.^ The solubilities
of this reducing substance are nearly identical with those of the active
physiological principle. It gives a dark green or blue colour with
ferric chloride, passing through purple to a dark red on the addition of
ammonia or sodium carbonate. With chlorine, bromine, or iodine water,
peroxide of hydrogen, or alkalis in the presence of oxygen, it gives a
rose-red colour, discharged by sulphide of hydrogen or ammonium sul-
phide. It is insoluble in alcohol, ether, or benzene; it is soluble in
water, alcohol iMis water, and dilute acids. It dialyses freely through
vegetable parchment. It is not a proteid, nor a carbohydrate, nor a
fat, nor is it affected by gastric digestion.

Manasse,^ who investigated the composition of the organ without
any special reference to the question of its physiological action, or the
work of Schafer and his colleagues, states that a reducing substance
is present, similar in many of its properties to jecorin (see p. 86). It
is, however, not jecorin ; the two substances are alike in some of their
solubilities, but the material from the suprarenal does not reduce
FehUng's solution until after prolonged boiling with sulphuric acid;
the sugar formed appears to be dextrose. Moore has, however, been un-
able to obtain from the suprarenal any substance that reduces Fehling's
solution. If one, moreover, compares the percentage composition of
Manasse's material with jecorin, the difference is seen to be striking, as
in the following; table : —


Substance from




c .

51 •32-51 -64



H .

8-11- 8-25

7-81- 8-09


N .


4-36- 4-88


S . - .

1-42-1 -47

2-14- 2-70


P .

2-2 -3-7

2-29- 2-75







S. Frankel ^ has also made an attempt to identify the active substance,
but with no better success than Moore ; according to him, the material
obtained by Manasse is inactive. Nabarro ^ has investigated the pro-
teids of the organ and found them similar to those of other glandular
structures, namely, cell globulin and nucleo-proteid. They appear to be
physiologically inactive. In his later work Moore ^ criticises Frankel's

^ " Proc. Physiol. See," London, March 1894 {Journ. Physiol., Cambridge and London,
vol. xvi. p. i) ; ibid., March 1895 (Joiwii. Physiol., Cambridge and London, vol. xvii. p.
ix. ) ; Journ. Physiol., Cambridge and London, vol. xvii. p. 230.

^ Compt. rend. Acad. d. sc, Paris, tomes xliii. and xlv.

^ Ztschr. f. physiol. Chem., Strassburg, 1895, Rd. xx. S. 478.

■4 IFien. med. PL, 1896, Nos. 14, 15, and 16.

■^ " Proc. Physiol. Soc," London, 1895, Journ. Physiol., Cambridge and London, vol. xvii.

" Jorirn. Physiol., Cambridge and London, 1897, vol. xxi. p. 382.


methods and results. He fiuds that absohite alcohol, which Frankel
used for extracting the active substance from the gland, only , dissolves
it in traces ; and that the prolonged action of alcohol, especially
if heat is employed, renders the material physiologically inactive,
though it still continues to give the colour reactions enumerated
above. He is inclined to consider the substance to be a derivative
of piperidine, not of pyrocatechin, as Frankel supposes. Piperidine
certainly produces a marked rise of blood pressure, like suprarenal

Pancreas. — Tlris organ is alkahne during hie, and rapidly becomes
acid after death. The solids are Uke those usually obtained from cellular
organs, namely, proteids (for the phospho-gluco-proteid separated from
the gland by Hammarsten, see p. 64); extractives (guanine,^ xanthine,
hypoxanthine, leucine,^ tyrosine, uric acid, lactic acid, inosite), and a
small proportion of inorganic salts.

Salivary glands. — The submaxillary gland yields proteids, of which
the most abundant is a nucleo-proteid ; * the cells also contain mucinogen,
which passes as mucin into the saliva. The parotid cells contain no
mucin. A small amount of mucin is, with gelatin, obtainable from the
investing connective tissue.

The kidneys. — Dming life the reaction of renal tissue is alkaline;
after death it rapidly becomes acid, especially the medulla.^

Grottwalt^ gives the following table relating to the percentage
composition of kidney tissue freed from blood : —

Proteids 11-185 to 12-217 per cent.

Gelatin 0-996 „ 1-849

Mucin Traces.

The following extractives have been obtained by various observers : —
xanthine, hypoxanthine, creature, taurine, leucine, cystin, urea, uric acid,
glycogen, and inosite.

The kidney also contains a small proportion of inorganic salts (Ol
to 0-7, Oidtmann).

The 'proteids of kidney tissue? — These are very like the proteids of
other glands, and consist of cell globulin, coagulable by heat at 52° C,
and a nucleo-proteid. This is far the more abimdant ; it coagulates at
63° C. ; it may be prepared by either the acetic acid or sodium chloride
method. It contains 0-37 per cent, of phosphorus, and produces, like
other nucleo-proteids, intravascular coagulation.

The lungs. — The chemical constituents of these organs call for no
special notice.^

The testis. — Chemically, the testis is mainly composed of proteids,

1 Tliis was shown independently by Tunniclilfe, Cenlralhl. f. PJwsiol. , Leipzis, 1897,
Bd. X. S. 777. ./ J > i s. .

^ Scherer, Ann. d. Cham., Leipzig, Bd. cxii. S. 276.

^ Virchow, Frerichs, and Stadeler, see Hoppe-Seyler, "Physiol. Chem.," S. 260. These
substances are present in the fresh organ, and are not, as in the spleen, the result of putre-

^ Hammarsten, Ztschr.f. physiol. Chem., Strassburg, Bd. xii. S. 163.

5 Halliburton, Journ. Physiol., Cambridge and London, 1892, vol. xiii. p. 806.
Liebermann states that the normal reaction of kidney tissue is acid. Arch. f. d. qcs. Physiol.,
Bonn, Bd. 1. S. 55.

® Ztschr.f. xiliysiol. Chem., Strassburg, Bd. iv. S. 431.

"^ Halliburton, loc. cit.

** " On Lecithin in Lungs and Sputum," see Zoja, Gaz::. med. di Torino, 1894,
vol. xlv.



or substances allied to proteids ; of the latter, nuclein and nucleo-
proteids are the most abundant.

As in other cases, the fresh gland is alkaline ; ^ the acidity noted by
Treskin ^ was probably the result of post-mortem changes. The extract-
ives which have been found are leucine and tyrosine (these are probably
post-mortem ^jroducts); lecithin, cholesterin, and fat (Treskin); creatine ;^
inosite '; * adenine, xanthine, hypoxanthine, guanine, ^ and other derivat-
ives of nuclein.'^

The salts present are chiefly chlorides of sodium and potassium

Semen. — The chief chemical constituent of the spermatozoa is nuclein
(Miescher, see p. 66). Miescher also prepared a base which he called
protamine, and to which Piccard^ ascrijjed the formula 0^J;1,^MJ^^.
Another organic substance, akin to a proteid, and containing 4 per cent,
of sulphur, was also described by Miescher.

Kossel^ has exanimed the protamine from the testis of salmon and stur-
geons ; he calls it salmine or sturine, according to its origin. He prepared
from it various crystalline salts, and a new base, C^iHylSTgOg, he terms
histidine. ^

Among other substances he prepared from fishes' spermatozoa, was thymin,
the substance he had previously got from the nucleic acid of the thymus
(see p. 66).

Lecithin, next to nuclein and proteids, is the chief organic substance
in spermatozoa.^*^ Cholesterin and fat are also fairly abundant. Miescher
gives the following percentage for the salmon's spermatozoa : —

]N"uclein .

46*68 per cent.

Lecithin .

7-47 per cent


. 26-76 „


. 2-24 „

Proteids .

. 10-32 „

Fat .

. 4-53 „

Miescher continued to work at this subject (salmon's spermatozoa)
throughout his life. He, however, never published much beyond his
early papers. After his death, Schmiedeberg published an article ^^
compiled from his numerous notes. This paper relates to the quantitat-
ive composition of the spermatozoa, and gives analyses of the principal
substances obtained from them, especially nuclein and protamine. He
considers these are in chemical union, thus :


(nucleic acid) (protamine)

The heads of the spermatozoa contain 60-73 per cent, of nucleic acid
and 19-78 per cent, of protamine. The tails (which are soluble in

1 Sertoli, Gazz. med.-vet., Milano, 1872, Anno ii.

■^ Arch. f. d. ges. Physiol., Bonn, Bd. v. S. 122.

^ Schottin, see Hoppe-Seyler, "Physiol. Chem.," S. 773.

■^ Schottin, Ktilz, Sitzungsb. d. Gesellsch. z. Beford. d. ges. Haturiv. zu Marburg, 1876,
No. 4.

^ Schindler, Ztschr. f. physiol. Chem., Strassbiirg, Bd. xiii. S. 438.

« Kossel, ibid., 1896, Bd. xxii. S. 172, 188 ; Hedin, ibid., S. 191.

^ Ber. d. deutsch. chem. Gesellsch., Berlin, Bd. vii. S. 1714.

* Loc. cit.

^ Hedin {loc. cit.) believes histidine is identical with a base he had previously obtained
in his work on the decomposition products of proteids.

'" Diaconow ; see Hoppe-Seyler's "Med. Chem. Untersuch.," Bd. ii. S. 221 ; iii. S. 405.

^^ Arch. f. exrpr.T. Path. u. Pharmakol., Leip/iig, 1896, Bd. xxxvii. S. 100.


saline solutions) contain, proteid, 41 '9; lecithin, 31 'To; fat and choles-
terin, 2 6 '2 7 j)er cent. In young spermatozoa some^ interest attaches
to the presence of a proteose which is regarded as the mother
substance of protamine. Proteose and protamine both give the biuret

Charcot's crystals. — These can be obtained from semen on evaporation.^
They are frequently found in sputum, in the blood, and in other situa-
tions, in leucocythsemia. Schreiner ^ considered that they consist of the
phosphate of a base he called spermine, C.^HjISr. Ladenburg and Abel ^

Fig. 12. — Charcot's crystals.

thought they were identical with ethylenimine, which can be prepared

artificially from ethylenediamine-hydrochloride. This identity, however,

is denied by Majert and A. Schmidt "^ and by Poehl.^ Poehl gives the

formula C5H14N2 to the base. He states that it is a normal constituent of

the testis, ovary, and blood, and that, used as a drug, it has a tonic effect.

Ovary. — The connective tissue element is large, and yields chiefly

gelatin and mucin. Proteids and nuclein are derived from the ova and

^ Bottger, Vircliow's ArcMv, Bd. xxxii. S. 525.

- Ann. d. C'hem., Leipzig, Bd. cxciv. S. 68.

■^ Ser. d. deutsch. chem. Gesellsch., Berlin, Bd. xxi. S. 758.

■* Compt. rend. Acad. d. sc, Paris, tome cxv.

5 Berl. Iclin. Wchnschr., 1893, No. 36.



other cells present. The corpora lutea are coloured by lutein. This is a
lipochrome (see p. 20). Thudichum ^ was the first to point out that it
is distinct from haeniatoidin, which is also generally present.

The constituents of eggs are descriljed with the various proteids,
etc., of which they are made up.


Skeletal muscle. — A muscle contains, besides the muscular fibres,
supporting connective tissue with fat. Each fibre consists of two parts,
the sheath or sarcolemma, and the contractile sul:)stance which it
encloses. The sarcolemma resembles elastin very closely in its

The contractile substance is of soft consistency, and contains a large
percentage of proteids, and smaller quantities of various extractives and
salts. By the use of a press a juice can be squeezed out of perfectly
fresh muscles, which is called the muscle flasma. Like blood plasma,
this coagulates, and the proteid clot is called myosin ; this occurring
within the body after death is the cause of rigor mortis.

Living muscle is alkaline ; but after extreme activity, and after
death, the reaction becomes acid ; this is due in part to the development
of sarcolactic acid.

The percentage of water in muscle varies in different animals : ^ —


72 to 74 per cent.

Birds . 70 to 76 per cent

Ox .


Amphibians 76 ,, 80 ,,



Fishes . 79 „ 82 „



Crab .85



Pecten . 79 „ 80 „

In young animals, and during inanition, the percentage of water is

Human muscle has the following average percentage composition : —

Water ........


Proteids, including sarcolemma, proteids of con-
nective tissue, vessels, and pigments
Gelatin ........


Extractives (creatine, lactic acid, glycogen, etc.)
Inorganic salts ......

This may be compared with the muscle of a mollusc {Pecten) : ^ —

73-5 per cent.

26 -.5











79-60 to 80-25 per cent.

Water .....


Proteids .....
Glycogen. ....
Glycocine ....

Ethereal extractives .
Inorganic salts ....

^ Centralbl. f. d. med. Wissensch., Berlin, ]S69, Bd. vii. S. 1.
- Ewald, Ztschr.f. Biol., Miinchen, Bd. xxvi. S. 1.

^ Sehlossberger, " Chem. der Gewebe," Leipzig and Heidelberg, ]S56, S. 169
Besanez, "Lehrbueh," 1878, S. 676; Hoi:)pe-Seyler, "Pliysiol. Chem.," S. 636.
■* Chittenden, Ann. d, Chem., Leipzig, Bd. clxxviii. S. 266.

20-40 „


15-68 „


2-43 „


0-71 „


0-33 „


1-26 „




Muscle considered as raeat is the most concentrated and most easily
assiinila1)le of the animal nitrogenous foods. It forms our chief source
of nitrogen. In 100 parts of nitrogen from beef, 77'4 come from proteid
insoluble in water, 10-08 from soluble proteid, and 12-52 from extract-
ives.^ In addition to the proteids, extractives, and salts contained in
muscle, the flesh used as food contains a certain variable percentage of
fat, even though all visible adipose tissue is cleaned off. In estimating
the amount of fat, Dormeyer^ recommends that the meat should be
subjected to artificial digestion before extraction with ether ; flesh then
yields an additional 0'75 per cent, of fat.

The following table ^ gives the chief substances in some of the principal
meats used as food : —















Solids ......







Proteids and gelatin





22 7









Carbohydrate ....














The flesh of young animals is richer in gelatin than that of old ones;
thus 1000 parts of beef yield 6, of veal 50, parts of gelatin (Liehig).

Meat contains four times the amount of proteid present in an equal
weight of milk.

The process of cooking meat (after it has been kept to allow rigor
mortis to pass off) renders the investing connective tissues looser,
separates the muscidar fibres, and destroys parasitic growths. The
muscidar fibres themselves, especially if boiled, are rendered more
difficult of digestion.

The muscle 'plctsm.a and the muscle sgrwrn.— Kllhne * was the first to
obtain muscle plasma ; he used frogs' muscle. The fresh blood-free
muscle is frozen and subjected to strong pressure, the expressed fluid
(muscle plasma) is filtered ; it is found to be syrupy in consistence, and
faintly alkaline. As the temperatm^e of the plasma rises to that of the
air, it clots, and the myosin, so formed, contracts to a slight extent,
squeezing out muscle serum. Kiihne found this latter fluid to contain —

(1) A proteid coagulating at 45° C. ; (2) an alkah albumin ; ^ (3) a
small quantity of albumin ; (4) extractives and salts.

A good many years later, I was successful in repeating these ex-
periments with mammalian muscle,^ and showed, moreover, that not only

1, CentralU. f. dj. iiwd. Wisscnscli., Berlin, 1894.

" Arch. f. d. gcs. Physiol., Bonn. 189.5, Bd. Ixi. S. 341 ; 1896, Bd. Ixv. S. 90 ; Schulze,
iUd., S. 299; 1897, Bd. Lxxii. S. 145.

3 Munk's "Physiologie," Aiifl. 4, S. 280.

* "Lehrbuch d. phy.siol. Chem.," S. 272; "Untersncli. li. das Protoplasma," Leipzig,

■' The natural alkali albumins described by older workers are no doubt all globulins.

" Halliburton, Journ. Physiol., Cambridge and London, vol. viii. pp. 133-202.


does cold prevent the coagulation of muscle plasma, but, as in the case of
blood plasma, admixture with solutions of neutral salts has the same
effect. Addition of water to the salted muscle plasma brings about
coagulation (an acid reaction making its appearance simultaneously),
especially at 40° C, and still more rapidly if solution of "myosin
ferment" is added. The myosin ferment was prepared from muscle
in the same way as fibrin ferment from blood serum.

Saline extracts of muscle which has undergone rigor mortis, resemble
salted muscle plasma very closely ; after dilution they undergo coagula-
tion; this may be a re-coagulation of the redissolved myosin, for the
acidity of the saline extract is increased by re-coagulation. Some
observers, however, regard this phenomenon not as a true re-coagulation,
but as a simple precipitation of the myosin by dilution with water.

Myosin may be most readily extracted from muscle by means of
ammonium chloride solution, and may be precipitated in a gelatinous
form by dialysing away the salt.^ Elementary analysis^ gives the
following results r-C, 5279; H, 712; N, 16-86; S, 1-26; 0, 22-97.

Eecent research has shown that calcium salts are essential for the
effective coagulation of milk and blood. The facts are not so positive
in the case of muscle, but there is some evidence pointing to the
existence of an analogy in the three cases. ^

By fractional heat coagulation, and by their varying solubilities in
different salts, I was able to separate four different proteids in the
muscle plasma.

(1) A globulin precipitable by heat at 47° C. This is analogous to
the cell globulin found in most protoplasmic structures. It is termed
musGulin by Hammarsten. 1 gave it the name parmnyosinogen.

(2) A globulin precipitated by heat at 56° C. This is the proteid
which is especially acted on by the myosin ferment, and is converted
into myosin. I termed it myosinogen : both it and paramyosinogen
contribute to the muscle clot.

(3) A third globulin precipitated at 63° C. {myoglobulin) is con-
tained in the muscle serum.

(4) Small quantities of an albumin {myoalhumin), similar in its
properties to serum albumin, are also present.

In addition to this, in the case of red muscles, there is hemoglobin ;
and if the muscle has been kept warm, and acidity developed, small
quantities of proteoses and peptone, which are formed by a process of
self-digestion. Briicke showed, many years ago, that muscle contains
small quantities of pepsin, doubtless absorbed from the gastric mucous
membrane ; this becomes active on the onset of acidity. The action of
such a ferment within the body will perhaps explain the phenomenon
called the disappearance of rigor mortis; it is unnecessary to suppose
that this is always due to putrefactive organisms,'* since rigor often dis-
appears before putrefaction sets in. Perfectly fresh muscle contains no
proteose or peptone.^

Whitfield also investigated the question whether myosin or its precursors are

1 Kiihne and Chittenden, Ztschr. f. Biol., Mlinchen, Bd. xxv. S. 358.

2 Chittenden, ibid. See also Stud. Lab. Physiol. Chem., New Haven, 1889, vol. iii.
p. 116.

^ Locke, Journ. Physiol., Cambridge and London, vol. xvii. p. 293 ; other references will
be found in this paper.

* Cossar Ewart, Proc. Physiol. Soc, London, 1887, p. xxv.
^ Whitfield, Journ. Physiol., Cambridge and London, 1894, vol. xvi. p. 487.
VOL. I. — 7


of the nature of nucleo-proteids. He found that they are not. He was indeed
able to obtain no nucleo-proteid at all from muscle. Pekelharing^ has taken
up the latter question, and by an improved method discovered that muscular
tissue does contain a small amount of nucleo-proteid. He points out that on
gastric digestion small quantities of nuclein are soluble, if the amount of
hydrochloric acid present exceeds 0"1 per cent. Whitfield used water as an ex-
tracting agent for any possible nucleo-proteid. Pekelharing points out that the
water will soon become acid from sarcolactic acid, and uses dilute (0'15 per cent.)
sodium carbonate solution instead. From such an extract the nucleo-proteid
can be precipitated by acetic acid. From 543 grms. of flesh he obtained 2 grms.
of nucleo-proteid. This substance produces intravascular clotting, and contains
0"7 of phosphorus. The nuclein split off from it contains 3 "5 per cent, of
phosphorus, and on decomposition yields alloxuric bases, especially xanthine
and guanine. Hypoxauthine and adenine were not found. Kossel ^ also failed
to get adenine from muscle.

An important research on muscle plasma and its proteids has lately
been published by v. Flirth.^ He obtained the plasma from blood-free
muscles by extracting them with physiological saKne solution. This
extract coagulates spontaneously, and the clotted proteid formed he calls
myogen fihrin or myosin fibrin. The proteids in the muscle plasma he re-
duces to three, namely, paramyosinogen, 17 to 22 per cent, of the total pro-
teid ; myosinogen or myogen, 77 to 83 per cent., and traces of an albumin.*

My work is confirmed in its main point, namely, that there are two
proteids in the muscle plasma, paramyosinogen and myosinogen, which
enter into the formation of the muscle clot ; the action of a specific
ferment to bring about this change was not specially investigated. The
principal new fact made out is, that paramyosinogen passes into the

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 14 of 147)