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sulphuric acid, water, and certain not fully oxidised products (urea, uric
acid, etc.) which contain the nitrogen of the original proteid.

Composition of the proteids. — Various proteids differ a good deal
in elementary composition, as is seen by the following percentages : —





From


From




Hoppe-Seyler.2


Drechsel.^


c


. 51-5 to 54-5


50-0 to 55-0


H


. 6-9 „ 7-3


6-8 „ 7-3


N


. 15-2 „ 17-0


15-4 „ 18-2





. 20-9 „ 23-5


22-8 „ 24-1


s


. 0-3 „ 2-0


0-4 „ 5-0



In addition to the above constituents, many proteids or proteid-like
substances contain small quantities of phosphorus ; and practically all
proteids leave on ignition a variable amount of ash. In the case of egg-
albumin the chief substances in the ash are chlorides of potassium and
sodium, and smaller quantities of phosphoric, sulphuric, and carbonic
acids, in combination with sodium, potassium, calcium, magnesium, and
iron. There may also be a trace of silica.* The ash of serum pro-
teids contains an excess of sodium chloride, and that of muscle proteids
a preponderance of potassium and phosphoric acid.

Whether these mineral substances are integral constituents of the proteid
molecule, or closely adherent impurities, is a matter of doubt ; the latter
supposition is the more probable, as there are certain methods of obtaining
proteids practically free from ash. The best of these is Harnack's,-^ in which
he precipitates the proteid as a copper albuminate ; this is dissolved in sodium
hydrate, and the proteid is precipitated from this solution by hydrochloric acid.
The so-called ash-free albumin obtained earlier by Aronstein and Schmidt ^ by
means of dialysis, was shown by later observers (Heynsius, Winogradoff) to be
poor in ash, but not free from ash, and, moreover, that its incoagulability by
heat and other characteristic properties were due to the use of alkali in its
preparation. Nevertheless, Harnack's ash-free albumin is also not coagulable
by heat, and more closely resembles acid albumin in its properties than any
other known proteid.''

1 A very suggestive article by Pfliiger on this subject will be found in Arch. f. d. ges.
Physiol., Bonn, Bd. xlii. S. 144.

^ " Handbuch d. pliysiol. path. chem. Anal.," 1885, .5th edition, S. 258.

^ Loc. cit. Klihne and Chittenden's analyses of peptones, which they give with reserve,
lie considerably outside these limits, Ztsclir. f. Biol., Miinchen, 1886, Bd. xxii. S. 452.

■* Gmelin, " Handb. d. org. Chem.," Bd. viii. S. 285.

'' Ber. d. deutsch. chem. Geselhch., Berlin, Bd. xxii. >S. -3046; Bd. xxiii. S. 3745 ; Bd. xxv.
S. 204.

" Arch. f. d. ges. Physiol., Bonn, 1875, S. 1.

"^ Werigo, ibid., Bd. xlviii. S. 127. Harnack denies that his material is acid-albunnn,
in spite of the acid used in its precipitation.



2 6 CHEMICAL CONSTITUENTS OF BODY AND FOOD.

Globin prepared from haemoglobin is stated to be free from ash. It is
perhaps hardly correct to say that the ash is an impurity, because it is
extremely probable that in their native condition the actual proteid molecules
are combined more or less loosely with inorganic substances.

The process of incinerating has its drawbacks in determining the amount
of ash in a proteid ; for in the heating, some of the sulphur of the proteid, and
when phosphorus is present the phosphorus also, will be oxidised and form
sulphuric and phosphoric acids respectively. H. Schulz ^ has recently shown
that sulphates are formed in tissues as a result of drying them at 110° C. ; this
would occur to a greater extent still at the temperature necessary for ignition.

The sulphur in proteids is in the body normally burnt off as
sulphuric acid, which leaves the body in the urine as sulphates. The
ethereal hydrogen sulphates of the urine originate in the intestine, as a
result of putrefactive changes in proteids,'^ and when putrefaction is
hindered by the administration of large doses of iodoform in dogs, these
products do not appear in the urine.^ Kriiger * has shown that a part
of the sulphur in proteids is present in a condition of stable combination,
a part loosely combined ; the latter is removed by boiling with alkalis,
the former is not ; the proportions of the two differ in different proteids.
Among the primary decomposition products of proteid, thio-acids, of
which thioglycoUic acid is probal)ly the most abundant, are obtained.^

From the elementary analyses which have been made of proteids, various
observers have attempted to construct an empirical formula for certain typical
proteids, egg-albumin being the one usually selected. Thus Lieberkiihn
assigned to albumin the formula C-2Hjj.2Njg022S ; Loew ^ gives the same
formula ; Harnack ^ gives C204H322N'52O(i6^2 J Schiitzenberger,^ Cl24oH.:jy2Ng;^075
S, ; and there have been others. The great divergence between these numbers
requires no comment.

Equally conflicting results have been obtained in attempts to ascertain the
molecular weight of albumin. Lieberkiihn, in 1852, attempted to establish it
by analysing the copper compound of egg-albumin ; more recently, Harnack
has done similar work. But very little importance can be attached to
such work at present, for Chittenden and Whitehouse^ find there is no
definite copper albuminate, but that there are several in the mixture ; and
equally variable results are obtained with other metals both with egg albumin
and myosin.

Such researches lead to the same conclusion as dialysis, namely, that
the molecules of proteid are extremely large, but leave us quite in the
dark as to their exact magnitude. ^*^ It is possible that in the future the

^ Arcli.f. d. ges. Physiol., Bonn, 1894, Bd. Ivi. S. 20;J. See also Halliburton and Brodie,
Journ. Physiol., Cambridge and London, 1894-95, vol. xvii. p. 154.

'•^ Bauniann, Ztsclir. f. ])hysM. ('hem., Strassbnrg, Bd. x. S. 123.

•^ Morax, iftwi, S. 318. See also more recently Nvittall and Tliievf'elder on "Animal
Life without Bacteria in the Alimentary Canal," ibid., vol. xxi. p. 109 ; xxii. p. 62. In this
paper it is shown that healthy animal life is possible without micro-organisms in the
alimentary canal.

,■* Arch.f. d. c/es. Physiol., Bonn, 1888, Bd. xliii. S. 244.

^ F. Suter, Zlschr. f. 2)hysiol. Chevi., Strassburg, 1895, Bd. xx. S. 564 ; E. Baumann,
ibid., S. 583, and VirchowsArchiv, 1894, Bd. cxxxviii. S. 560 ; E. Salkowski, ibid., S. 562.

" Loew and Bokorny, "Die cheniisclie Kraftquelle im lebendcn Protoplasma," Munich,
1882.

'' Ztschr. /. 2)hyswl. Chem., Strassburg, Bd. v. S. 207.

^ Bull. Sac. chim., Paris, Scr. 5, tomes xxiii. and xxiv. See also Scliniiede1)erg, Arch. f.
exper. Path. u. Pharmaknl., Leipzig, 1897, Bd. xxxix. S. 1.

^ Stiui. Lab. Physiol. Chem., New Haven, vol. ii. p. 95.

1" The large size of the proteid molecule can be very strikingly demonstrated liy the fact



COMPOSITION OF THE P ROTE IDS. 27

result will Ije achieved, when proteids oljtainaljle in a crystalline form
have been thoroughly investigated.

Vegetable proteids have been prepared in a crystalline form^ in
combination with magnesia; Drechsel"^ found in one preparation 1-4 per
cent, of magnesia (MgO) ; in another, prepared by an improved method,
1-43 per cent. From this the molecular weight x may Ije calculated as
follows : —

a;_ 100 -1-43 . ^_97.7

.From the similar examination of the sodium compound the mole-
cular weight of albumin was found to be 1496. Other vegetable pro-
teids examined by Grilbler^ also gave high but varialjle molecular
weights.

Haemoglobin belongs to the proteid compounds capable of crystallisa-
tion; Zinoffsky* prepared haemoglobin crystals from the blood of the
horse in a very pure state, and the formula calculated for haemoglobin
from his elementary analyses would be —

C712Hn3oNi^0245FeS2

If a molecule of ha:;matin, C32H32N404Fe, is subtracted, the formula for
proteid left is —

Jaquet's^ formula for pure haemoglobin of dog's blood would give the
proteid molecule a formula —

So that here again there are great discrepancies.

Such a summary of the principal analyses made, is quite sufficient to
give point to Drechsel's conclusion, that while divergences of analysis
exist, even though they are due to extremely small errors, it is futile
to attempt to measure accurately the size of the proteid molecule.
Drechsel points out that in so large a molecule an analytical error of
O'Ol per cent, would have the same importance as one of O'l per cent, in
ordinary analyses.

It should be added, in conclusion, that some few investigators have
used the cryoscopic method in attempting the solution of this problem ;
the molecular weight of egg-albumin by this method is 14,000
(Sabanejeff),'^ of albumoses 1200-2100, and of antipepton much less
(Paal).7

Equally inconclusive, though much more interesting, have been the
attempts to discover the rational formula for the proteid molecule. The

that proteids in solution will not pass through a membrane of gelatin or silicic acid, when
filtered under pressure. The products of proteolysis (proteoses and peptones) will,
however, pass such a membrane ; the smaller size of their molecules has also been demon-
strated by the cryoscopic method. Crystalloids pass through such membranes at the same
rate as water, and can thus be easily separated from colloids in a solution containing both
(C. J. Martin, Journ. Physiol., Cambridge and London, 1896, vol. xx. p. 364).

1 The subject of vegetable and crystalline proteids will be treated at length in a later
section of this chapter.

' Jimrn. f. 'prctkt. CJiem., Leipzig, 1879, N.F., Bd. xix. S. 331.

^ Ibid., 1881, Bd. xxiii. S. 97.

^ ZUdir. f. 'pliysiol. Chem., Strassburg, 188.5, Bd. x. S. 16. « Inaug. Diss., Basel, 1889.

'^ Ber. d. deuUch. chcm. Ge^iellsch., Berlin, 1891, Bd. xxiv. Ref. 558.

"^ Ibid., 1894, Bd. xxvii. S. 1827. For Siegfried's work on the identity of antipeptone
with a simple compound, whicli he has called carnic acid, see under " Chemistry of Muscle,"
p. 103.



2 8 CHEMICAL CONSTITUENTS OF BODY AND FOOD.




usual method which a chemist follows in attempting to unravel the
constitution of any substance, is first to discover the way in which it decom-
poses (analysis), and then to build up the original material once more from
the simple compounds so obtained (synthesis). In the case of the proteids
there have been many observations on the analytical side, but synthesis
has not yet been successful. We will first consider the results of
analysis, next the attempts at synthesis, and finally state some of the
theories founded on these observations.

The decomposition prodticts of proteids. — The experiments which

have been performed fall into two
main groups : the first, designed with
a view to determine the series of
changes a proteid undergoes in its
passage through the body ; the second,
with the object of investigating the
chemical substances obtained as
cleavage products by artificial means
in the laboratory. In the first group
the progress which has been made
is slight, great and obvious difficulties
being encountered at nearly every
step ; the end products, carbonic
anhydride, water, urea, uric acid,
ammonia, etc., are known, but the
intermediate substances, resulting
from metabolic changes within the
cells and tissues, are still in the
region of conjecture.
In the alimentary canal itself there are, however, changes which are

within the grasp of the investi-
gator, and the proteoses, al-
buminates, and peptones there
formed will be treated under
the head of " Digestion." Here,
too, under the prolonged action
of the pancreatic juice, simpler
nitrogenous substances, such
as leucine, tyrosine, aspartic
acid, and ammonia, are formed
in small quantities. Leucine
(CeHi.N^O) is empirically
amido-caproic acid, but of the
numerous possible isoinerides
which could be included under
that name, leucine " has
been shown to be a-amido-
isobutylacetic acid, (CH3),CH.
CH, CK, (NHo) COOH. ' "The
leucine obtained on pancreatic
digestion is dextrorotatory.
Levorotatory and optically in-
active varieties of leucine exist,
and some of them have been



Fig. 7. — Leucine crystals. — After Klihne.




Fig, 8.— Tyrosine crystcals. — After Frey.



THE DECOMPOSITION PRODUCTS OF PROTEIDS. 29

prepared synthetically.^ Tyrosine (CjHuNOs) is oxyphenyl amidopropionic
acid, HO.CeH4.C2H3(NH2).COOH. This substance has also been made
synthetically.^ The crystalline forms of these two substances are seen in
the accompanying figures (Figs. 7 and 8). Aspartic or asparaginic acid ^
(C4H-NOJ is amido-succinic acid, C2H.(iSrH2)(COOH).^. That ammonia
is produced in prolonged panareatic digestion, under conditions preclud-
ing the possibihty of putrefaction, was shown by Stadelmann.^

To this Kst must be added lysine, lysatinine, arginine^ (see p.
33), glutaminic acid, and proteinchromogen,*^ a substance of un-
certain nature which gives a reddish-violet product with chlorine or
Ijromine water.

Within the intestine many changes occur which are due to Ijacterial
action. The products which have just been enumerated arise first,
and then by different changes other substances are formed ; of these
the following may be mentioned : — indol, skatol, skatol-carbonic acid,
oxyphenylpropionic acid, phenylpropionic, and phenylacetic acids,
parakresol, and phenol, and simpler bodies hke carbonic anhydride,
water, ammonia, hydrogen, and sulphm^etted hydrogen, amido-fatty acids,
and fatty acids themselves.'^ The most interesting point to note here
is the large number of derivatives containing the benzene nucleus. The
indol group has never been obtained from the proteid molecule by any
other method than that of bacterial decomposition.^

We can now pass to the second category of investigations, namely,
those carried out in vitro.

The first action produced by most reagents, especially if they bring
about hydrolysis, is the formation of proteoses and peptones ; these are
then broken up into more simple substances. The subject may be most
conveniently treated of under the heads of the different methods employed.

1. Treatment with alkalis. — IMulder ^ treated albmnm with caustic
potash, and obtained the substance which we now call alkah-albumin ;
this material is free from most of the sulphur present in the original
proteid, namely, that which is present in loose combination ; the firmly
combined sulphur, however, remains undistmbed.^*'

iMulder thought that by this method he had obtained the base of
all albuminous material, and called it " protein " ; he described many

^ For recent literature on lencine, see Schulze and Likiernik, Ztschr. f. physiol. Chcm.
Strassburg, Bd. xviii. ; Gmelin, ihid., Bd. xviii. ; Hiifner, "Synthesis of Leucine," Journ. f.
prakt. C'hem., Leipzig, N. F., Bd. i. ; E. Scliulze, Barbieri and Bosshard, Ztschr. f. 2?hi/siol.
Cliem., Strassburg, Bde. ix. and x. ; Cobn, ibid., Bd. xx.

- Erlenmeyer and Lipp, Her. d. deiotsch. diem. Gesellscli., Berlin, Bd. xv. S. 1544.

'"' For cliemistry and preparatioir, see Hlasiwetz and Habermann, Ann. d. C'hem.,
Leipzig, Bd. clxix. S. 160 ; E. Selrulze, Ztschr. f. physiol. Chevi., Strassburg, Bd. ix.

* Ztschr. f. Biol., Mlinclien, 1888, Bd. xxiv. S. 261. See also Hirscliler, Ztschr. f.
physiol. OJiem., Strassbui'g, Bd. x. S. 302.

5 Hedin, Arch./. Physiol., Leipzig, 1891, S. 273.

^ Stadelmann, Ztschr. f. Biol., Mttnclien, Bd. xxvi. S. 491. K'eumeister suggests the
name tryptophan for this substance, ibid,., S. 324 ; ISTencki, Ber. d. dcutsch. chem. Gcscllsch.,
Berlin, Bd. xxviii. S. 560.

■^ Salkowski, ibid., Bd. xii. S. 648; Tappeiner, Zt'<chr. f. Biol., Mlmchen, Bd. xxii.
S. 236.

* For recent ivork on the mycological processes in the intestines, see Y. D. Harris,
Journ. Path, o.nd Bactcriol., Edin. and London, 1895, vol. iii. p. 310. On the putrefaction
of pure proteids see 0. Emmerling (i?«'. d. dcutsch. chcm. Gesellsch., Berlin, 1896, Bd. xxix.
S. 2721) ; in addition to the substances enumerated above he finds betaine.

^ Journ. f. prakt. Chcm., Leipzig, Bd. xvi. S. 129; Bd. xvii. S. 312; Ann. d. Chem.,
Leipzig, Bd. xxxi. S. 129.

"• Kriiger, Arch. f. d. ges. Physiol., Bonn, Bd. xliii. S. 244.



30 CHEMICAL CONSTITUENTS OF BODY AND FOOD.

compounds of this substance, but, as Liebig^ was the first to show,
this work was full of fallacies, and the only remnant of it is the survival
of the word proteid.

Pavy"2 has used caustic potash in his researches on proteids, and
shown that the action of the alkali is to split oft' a substance of an amylose
nature which, on further treatment with mineral acids, yields a reducing
but non-fermentable sugar, Q^Jd^, which gives a crystalline osazone
with phenylhydrazine. Pavy, however, himself points out that he is
not the first to obtain this result. Schiitzenberger ^ many years ago
oljtained from proteid a dextrm-like substance by the prolonged use
of baryta water, which, after treatment with sulphmic acid, reduces
Fehling's solution, and " appears to be glucose, or an analogous suljstance."
From his own and Schiitzenberger's work, he draws the conclusion that
proteid matter has the constitution of a glucoside. These experiments
will 1)6 again referred to under the gluco-proteids.

0. Nasse ^ discovered that by boiling proteids with a strong solution
of barium hydrate some of thek nitrogen was disengaged as ammonia,
but this only accounted for a small percentage of the total nitrogen.
He concluded that the nitrogen which is readily liberated is in the form
of an amide, that some is combined similarly to that of creatine, but that
the major part which is unaffected by this treatment is in the form of
an amido-acid.

Schiitzenberger ^ has elaborated the baryta method. He obtained dif-
ferent residts by varymg the conditions of temperatm^e and pressure, of
the time of treatment, and of the amount of bariiun hydrate employed. In
his earher researches he employed coagulated egg-white, which had been
thoroughly washed with water, alcohol, and ether ; weighed amounts of
it were treated with from two to six times theu' weight of crystalhsed
barium hydrate and with water, the whole bemg heated in a closed iron
vessel to temperatures ranging from 100° to 250° C, and for periods of
time varying from 8 to 120 hom-s. He found that nitrogen to the extent
of about one per cent, of the total weight of albumm is given off as
ammonia at atmospheric pressm-e, by boiling for half an hour : a second
one per cent, comes off' slowly by continued boiling for 120 hours (this
result is, however, more easily obtained by treating with three parts of
barium hydrate at 120° C. for six to eight hours) ; a thu-d one per cent, is
given off" by treating with two parts of barium hydrate at 150° C, and a
fom'th one per cent, by heating with excess of barium hydrate at 260° C.

He next found that accompanying these four stages there were
different cleavage products obtained. Fh'st, some insoluble bariiun salts,
namely, oxalate, carljonate, phosphate, and sulphate. On calculating
the quantities of oxalate and carbonate formed, he arrived at the
interesting result that they were present in proportions to support the
hypothesis that, with the ammonia set free, they had existed in the pro-
teid molecule as a urea and oxamide radicle. The barium carbonate
and oxalate, moreover, were formed at different stages of ammonia

^ Ami. d. C'hevi., Leipzig, Bd. Ixii. S. 132.

-"Physiology of the Carbohydrate-s," London, 1894, p. 2S ; Froc. Ruy. Soc.
Loiuion, 1893, voL liv. p. 53 ; Ecj}. Brit. Ass. Adv. Sc, Loudon, 1896.

^ Bull. Soc. chim., Paris, 1875, Ser. 5, tome xxiii. p. 161.

4 Cheni. Centr.-Bl. Leipzig, 1873, S. 137; Arch. f. d. ges. Physiol., Bonn, Bde. vi. S.
589 ; vii. S. 139 ; viii. s. 381.

■' ^71)1. dechim., Paris, S^r. 5, tome xvi. p. 289 ; Comjot. rend. Acad. d. sc, Paris, tome ci.
p. 1267 ; cii. p. 289 ; cvi. p. 1407 ; cxii. p. 189 ; Bull. Soc. chim., Paris, Ser. 5, tome xxiv.



THE DE COMPOSITION PR OD UCTS OE PR O TEIDS. 3 1

elimination, in such a way that the first amount of ammonia might be
considered to come from one of the amide radicles of the oxamide, while
the second corresponded to the urea, and the third to the remaining
nitrogen of the oxamide, then present as oxamic acid.

After precipitating the barium with carbonic anhydride and sulphuric
acid, he obtained, by distillation in a partial vacuum, a small quantity of
acetic acid, traces of formic acid, and an essential volatile oil which he
indentified as pyrrol contaminated with smaller quantities of methyl-
pyrrol and ethyl-pyrrol. The remainder, which did not volatilise
nor sublime at a low temperature, he termed rSsidu fixe. By con-
trasting the composition of this with that of the original albumin,
and taking into account the substances already ermmerated, he found
that the essential action of the barium hydrate was that of
hydrolysis. By repeated crystallisations from water, alcohol, and
ether, he separated the constituents of his r^sidu fixe and found
they were amido-acids of two classes, which we may term A and B.

A. These comprised over 80 per cent, of the total weight ; in them
the proportion ]Sr:0 = 1:2. They consisted of —

1. Amido-acids of the series C^Hgn+iNOg.

These he called leucines. They included alanine (C = 3) in small
quantities, propalanine or amidobutyric acid (C = 4), butalanine or
amidovaleric acid (C = 5), both in considerable amount, and leucine or
amidocaproic acid (C = 6), in very large quantities. Glycocine or amido-
acetic acid (C = 2) was not found.

2. Amido-acids of the series CjjH2n_iN20.

These are amido-acids of the acrylic series, and were called leiie'eines.
Here, too, the term which was most abundant is that in which C = 6, but
bodies corresponding to = 4 or 5 were also found.

3. Amido-acids of the series 0^11211^204, or some multiple of this.
To these su.bstances he gave the name of glue -proteins, on account
of their sweet taste. The most abundant of these were those in which
= 9 or 7, or some multiple of these numbers ; but others in which
= 8, 10, and 11 were also isolated.

B. These comprised about 16 per cent, of the total weight ; in them
the proportion ]Sr:0 = 1:3, or 1:4, or 2:5. In this class were found —

1. Tyrosine ; the amount of this was about 3"5 per cent.

2. Tyroleucine, 07H^ISr02, in about the same quantity.

3. Very small quantities of glutaminic acid, O5H9NO4. This is an
optically inactive amido-derivative of one of the pyrotartaric acids
(glutaric).

Of these substances, Schiitzenberger found varying quantities,
according to the degree to which the hydrolytic decomposition had been
carried out. The more thorough the hydrolysation, the more leucines
and leuceines were found ; but in earlier stages gluco-proteins were
in excess.

With other proteids he obtained corresponding results. G-elatin
gave the same substances, with the addition of amido-acetic acid or
glycocine ; 20 to 25 per cent, of this substance was obtained.

He concluded that the albumin molecule, under the action of barium
hydrate, loses ammonia, carbonic anhydride, acetic and oxalic acid, and,
becoming hydrated, forms in the first instance gluco-proteins, mainly
those in which 0=9, or some multiple of this, and that on further action
these are changed into leucines and leuceines.



32 CHEMICAL CONSTITUENTS OE BODY AND EOOD.

2. Treatment vnth acids. — Prolonged heating of proteids with dilute
acids results in thek hydration and the formation of jjroteoses and
peptone.^ Strong acids produce the same effect at the ordinary tempera-
ture in the course of a few days.^ This method has the disadyantage
that strongly coloiu'ed materials make then- appearance, and to avoid
this Hlasiwetz and Habermann^ introduced the important modification
of heating with strong hydrochloric acid and stannous chloride, by which
pale yellow solutions were obtained without a trace of charring. A
certain amount of reduction occurred during the operations, leadmg to
the formation of stannic chloride. These methods pelded the following
substances : —

(1) Ammonia ; (2) an amido-acid of the acetic series, namely, leucine ;
(3) two amido-acids of the acrylic series, namely, asparaginic acid
(C4H-NO4, amido-succinic acid), and glutaminic acid (C5HgN04, amido-
pyrotartaric acid), both in considerable amount; (4) tyrosine or
oxyphenylalanine.

Eittliausen ^ was the first to separate glutaminic acid aud asparaginic acids
from proteids. He and Kreusler suggested that glutaminic acid was a tj^pical
product of vegetable proteid ; but Hlasiwetz and Habermann ^ obtained it from



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