CHAPTER X.

THE PROTEIDS

THE proteids are the most important substances that occur in animal and vegetable organisms; none of the phenomena characteristic of life occur without their presence. They are invariable and constant constituents of protoplasm.

The term proteids was originally given to these substances by Mulder (poretov, pre-eminence), and the name is a convenient one in which to include all the heterogeneous members of the group. It must not be supposed that in adopting Mulder's nomenclature we in any way accept Mulder's theory of the constitution of proteids, which will be referred to later.

The expressions 'proteid' and 'albuminous substance' are synonymous. The word 'albumin' is restricted now to a definite class of proteids. The word 'albuminoid' should be restricted to a class of compounds (gelatin, mucin, &c.), which, although having certain resemblances to the proteids, differ from them in many important points. The words albuminate, albumose, albumid, &c., are applied to certain derivatives of the proteids; these terms should always be most carefully used, as their similarity to one another is apt to give rise to confusion.

The following short description of the proteids must serve in lieu of a logical definition; for although the proteids are the most important of all organic substances, they are those about which we have the least information.

'Proteids are highly complex and (for the most part) uncrystallisable compounds of carbon, hydrogen, oxygen, nitrogen, and sulphur, occurring in a solid viscous condition, or in solution in nearly all the solids and liquids of the organism. The different members of the group present differences in physical and to a certain extent even in chemical properties. They all possess, however, certain common chemical reactions, and are united by a close genetic relationship (Gamgee).'

1 Physiol. Chem. p. 4.

The following table from Gorup-Besanez' exhibits the proportion of proteids contained in the liquids and solids of the body:

The proteid constituents of the animal body are derived from vegetables, either directly, or indirectly through the body of another animal. Synthetic processes do occur in the animal body, but to a much greater extent in vegetables. Here the proteids are built up from simpler compounds derived ultimately from the soil and the atmosphere. In animals the proteids are first converted into substances called peptones, in which form they are absorbed ; the peptones are reconverted into proteids similar to those originally ingested, and these proteids are assimilated, that is, become part of the living organism. During life, however, there is not only a process of building up going on, but also a process of breaking down, the two constituting what is known as metabolism. The result of the destructive metabolism of proteids is the formation of various oxides, carbonic acid and water, and certain not fully oxidised products (urea, uric acid, &c.) which contain the nitrogen of the original proteid.

COMPOSITION AND CONSTITUTION OF THE PROTEIDS

The various proteids differ a good deal in elementary composition. Hoppe-Seyler gives the following percentages :

From figures of this kind various observers have attempted to construct an empirical formula for certain typical proteids, egg-albumin being the one usually selected. Thus Lieberkühn assigned to albumin the formula C,,H112N18O22S; Loew2 gives the same formula; Harnack3 gives C204H322N52066S2; Schützenberger C240H392N63073S3, and there

1 Lehrbuch, p. 128.

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? Loew and Bokorny, Die chemische Kraftquelle im lebenden Protoplasma, Munich, 1882. 4 Bull. Soc. Chim. vols. xxiii. and xxiv.

3 Zeit. physiol. Chem. v. 207.

have been others. The great divergence between these numbers requires no comment.

Results which are equally conflicting have been obtained in attempts to ascertain the molecular weight of albumin. Lieberkühn, in 1852, attempted to establish it by analysing the copper compound resulting from the action of a soluble copper salt on a solution of egg albumin. This compound has since then been analysed by six different investigators and found to contain from 1.5 to 5.2 per cent. of CuO. The compound formed is thus one which contains no definite quantity of copper, or there may be several copper albuminates in the mixture. Chittenden and Whitehouse' have both with egg-albumin and myosin found equally variable results with other metals. Therefore, although the molecular weight of albumin is undoubtedly very high, no accurate measurements have as yet been made.

Still more contradictory and mutually destructive theories have been formed with regard to rational formulæ for the proteids. The usual method which a chemist follows in attempting to discover the constitution of any substance is first to observe the way in which it decomposes under certain circumstances (analysis), and then if possible to build up the original material from the simpler compounds so obtained (synthesis). In the case of the proteids there have been many observations of the nature of analysis, but synthesis has not yet been successful. The various theories that have been formed all depend on the results of the decomposition of proteids, and here we meet with many difficulties. First, because the products of decomposition are so numerous; secondly, because under differing circumstances they are so various; and, thirdly, because in all probability living proteid differs in its constitution from the non-living proteid, with which necessarily laboratory experiments have to be made. Metabolism is a very different process in its results from those of experimental chemistry. Before going into the theories themselves it will be necessary to give a list of the products of decomposition which result from different treatment of albumin.

(1) In the body. Carbonic acid, water, urea are the chief final products. Glycocine, leucine, uric acid, &c., are probably intermediate products. Carbohydrates (glycogen) and fats may also originate from proteids.

(2) Action of heat. The oily liquid (Dippel's oil) obtained by dry distillation contains ammoniacal salts of the fatty acids, amines, and aromatic compounds.

(3) Putrefaction.

Ammonia, ammonium sulphide, carbonic acid,

1 Studies from the Lab. Physiol. Chem. Yale Univ. ii. 95.

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volatile fatty acids, lactic acid, and amido-acids (leucine, tyrosine, &c.). Indole and skatole.

(4) Action of strong mineral acids and caustic alkalis. The chief products are leucine, tyrosine, aspartic acid, and glutamic acid. (5) Action of baryta water in sealed tubes. (See further Schützenberger's theory, next page.)

(6) Action of oxidising agents. With nitric acid a yellow substance called xanthoproteic acid is first formed. As the constitution of albumin itself is unknown, that of its compounds is much more involved in obscurity. In spite of this, various substances have been prepared as the result of the action of nitric acid on albumin, and names trinitroalbumin, hydroxytrinitro-albumin, hexnitro- and hexamido-albumin sulphonic acids,' &c., with formulæ have been given, to them. It need hardly be said how exceedingly uncertain all this is, and that different analysts give different results. By oxidation with potassium permanganate, Maly obtained a substance to which he gave the name oxyprotosulphonic acid. These substances on further oxidation break up into simpler compounds like those already enumerated (fatty acids, amido-acids, aromatic bodies).

From results such as these, in which we see that amides, aromatic substances, and fatty derivatives are the most abundant, Gautier3 concludes that the different proteids differ in the arrangement, relation, proportion, and in some cases even in the nature of their contained radicles.

We can now pass on to consider briefly the various theories that have been held with regard to the constitution of the proteid molecule.

a. Mulder's theory. -Mulder observed that by the action of caustic potash, sulphur was removed from a proteid, and he called the sulphur-free residue protein, and ascribed to it the formula C36H26N4O10He considered that the different proteids were combinations of protein with different amounts of sulphur. Liebig and others pointed out that the warming of a proteid with potash removes not only sulphur, but also ammonia; and even though the residue gives no further colour with lead salts, it still retains some sulphur. It is thus possible to speak of two forms of sulphur in proteid, that which is loosely and that which is firmly combined. Further investigation has clearly shown that

1 Loew, J. pr. Chem. (2) iii. 180.

* Centralbl. med. Wiss. 1885, 740. Maly's Jahresb. xviii. 10.

3 Chimie appliquée à la physiol. i. 253.

4 Ann. Chem. Pharm. lxi. 121.

5 Danilewsky, Zeit. physiol. Chem. vii. 440. A. Krüger, Pflüger's Archiv, xliii. 244. In the latter paper will be found an interesting series of suggestions as to the way in which these two forms of sulphur are combined.

'protein' is an artificial product, very much like what we now call alkali-albumin. The sole remnant of this theory now extant is the word 'Proteid.'

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b. Schützenberger's theory.-Nassel was the first who attempted to get an insight into the molecular constitution of the proteids by treating them in sealed tubes with baryta water at a high temperature for many hours. He found that the nitrogen was differently combined, part being easily displaceable and part held firmly. Schützenberger has carried on researches in the same direction. He found that the products of decomposition are ammonia and carbonic acid in the same ratio as would result if urea were treated in the same way; other volatile products (pyrrole, indole, acetic acid, &c.), and a fixed residue in which the substances most abundantly present were leucine and tyrosine the latter containing the aromatic radicle. Other substances also of the nature of amido-acids were found. These amido-acids he classifies into two groups-the leucines, or amido-acids of the acetic series (CH+NO2), and leuceines, or amido-acids of the acrylic series (CH2-1 NO2). Both leucines and leuceines are produced by the splitting up of bodies of the formula CH2NO, (m=10 or 12), which have a sweet taste and are therefore called gluco-proteins. Albumin is regarded as a ureide, or compound of urea; the urea is combined with gluco-proteins and the gluco-proteins split up on hydration into amidoacids. The nitrogen is thus after hydration combined as NH2 (amidogen); in the proteid itself the nitrogen is probably present as NH (imidogen).

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c. Pflüger's theory. Although the distinction between living and non-living proteids was emphasised by John Fletcher in 1837, it was not until 1875 that an intelligible theory to explain such difference was advanced by Pflüger. The non-living proteids, such as are contained in white of egg, are stable and indifferent to neutral oxygen; but when these proteids are assimilated, that is, become part of a living cell, the molecules of proteid live by breathing oxygen; not necessarily oxygen from without, as frogs kept in chambers free from oxygen will continue to live for many hours. The assimilation of a proteid is probably due to the formation of ether-like combinations between the molecules of living proteid and the isomeric molecules of the food

Pflüger's Archiv, vi. 589.

2 Bull. Soc. Chim. vols. xxiii. and xxiv.; Annales de Chim. et Phys. (5) xvi. 289; and a large number of papers in the Compt. rend. In a recent paper, Compt. rend. ci. 1267, the formula for albumin given is simpler than those adopted in his earlier work; it is CH4NO10. More recently still (C. R. cvi. 1407) he has succeeded in preparing lenceine synthetically.

3 Rudiments of Physiology, Edinburgh, 1837.

4 Pflüger's Archiv, x. 251.