Frank Pell Underhill.

The physiology of the amino acids online

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Courtesy of Prof . L. B. Mendel



mi <>y/J nsav/Jod tejntnoo srfj worfa H bfi A

>Bd ,e ( [ioiilw'1o sno.s^B

^rid ,ii '^ ^MtBtgB 3

i ,H ,JBI bsiajf.

A and B show the contrast between two rats of the same
age, one of which, B, has been stunted. The lower two pictures
afford a comparison between two rats of the same weight, but
widely differing in age. The older, stunted rat, B, has not lost
the characteristic proportions of the younger animal, C.




Professor of Pathological Chemistry, Tale University








=Fir&t printed, Npyenjbeiv 1915, 1000 copies


During the past few years the physiology of the
amino acids has been subjected to much experimenta-
tion with the result that these protein cleavage prod-
ucts have assumed an ever increasing importance in
the problems associated with nitrogenous metabolism.
Owing largely to our too recent appreciation of the
significance of these substances in metabolic processes
there exists at present no compilation which fur-
nishes an adequate conception of the roles which may
be played by the amino acids. It has been, therefore,
the aim of the writer to gather together in one place
the results which have thus far been obtained in the
field of the biochemistry of the amino acids, thus
affording the busy practitioner, and others whose
resources for consulting original communications are
limited, an opportunity of gaining a knowledge of the
present-day problems in this field of nutrition. In the
accomplishment of this purpose the writer has made
no effort to include all the details or all the literature
available upon a given topic, but has sought rather to
indicate leading lines of thought. At the end of each
chapter are given references in which all the impor-
tant literature upon the topic discussed is cited.

It is assumed that the reader is familiar with the
fundamental principles of metabolism, hence, in gen-
eral, these have been omitted.

The author is deeply indebted to Professor Lafay-
ette B. Mendel for suggestions, criticisms of the
manuscript and for some of the plates presented.



Chapter I. PAGE

The Proteins and their Derivatives, the Amino
Acids 1

Chapter II.

Digestion, and Bacterial Activity in Relation
to the Amino Acids ..... 28

Chapter III.

The Absorption of Proteins and Amino
Acids 46

Chapter IV.

In What Form Does Ingested Protein Enter
the Circulation? ..... 58

Chapter V.

Theories of Protein Metabolism ... 81
Chapter VI.

The Further Fate of Amino Acids . . 99
Chapter VII.

The Amino Acids in Relation to the Specific
Dynamic Action of Proteins . . .120

Chapter VIII.

The Amino Acids and Simpler Nitrogenous
Compounds as Foodstuffs . . . 126

Chapter IX.

The Specific Role of Amino Acids in Nutrition
and Growth 136

Index 159


Plate. Photograph of mice . . Frontispiece


Figure 1. Survival periods of mice on diet of
zein and tyrosine and zein and
tryptophane .... 140

Figure 2. Growth curve of normal white rats 144

Figure 3. Growth curve with casein and milk

diets 144

Figure 4. Growth curve with milk diet . . 145

Figure 5. Maintenance on casein and growth

after addition of protein-free milk 146

Figure 6. Resumption of growth after addi-
tion of protein-free milk to casein
diet 147

Figure 7. Failure of growth on gliadin plus

protein-free milk . . . 149

Figure 8. Recovery of the capacity to grow

after a period of stunting . . 150

Figure 9. Maintenance and fertility on a

gliadin diet . . . .151

Figure 10. Indispensability of lysine for

growth 153

Figure 11. Failure of zein to maintain or pro-
mote growth .... 154

Figure 12. Indispensability of tryptophane for

maintenance in nutrition . .156

Figure 13. Growth on diets containing zein +

tryptophane + lysine . .157





The presence of nitrogen as a fundamental con-
stituent of protoplasm attests the supreme importance
of this element for the construction of living matter
and the continued existence of organized life. It is
well recognized, however, that all forms of nitrogen
are not equally available for the maintenance of
physiological rhythm. In support of this may be cited
the fact that although the animal organism is con-
tinually surrounded by an atmosphere rich in nitrogen,
little or none of this nitrogen can be utilized by the
body for nutritional purposes. The organism pos-
sesses discriminating powers and demands nitrogen
in a specific form, namely, such as that peculiar to
protein and its derivatives. Protein material con-
stitutes therefore an essential foodstuff and without
it life would be impossible for any considerable period
of time. "It is the chemical nucleus or pivot around
which revolves a multitude of reactions characteristic
of biological phenomena."


Vi'eWed 'from the chemical standpoint protein is
seen ajs; a ihrige molecule, complex in structure, labile
in character and therefore prone to chemical change.
So large and intricate is the make-up of the molecule
that chemists for generations have been baffled in
their attempts to gain any adequate conception of its
nature. At the present stage of our knowledge it is
impossible to form any satisfactory definition of a
protein based either on its chemical or physiological
properties. In general, proteins contain about 15 to
19 per cent of nitrogen, 52 per cent of carbon, 7 per
cent of hydrogen, 23 per cent of oxygen and 0.5-2.0
per cent of sulphur. Some also contain phosphorus
or iron. They act like amphoteric electrolytes, that
is, they are capable of forming salts with both acids
and bases. Proteins belong to that class of substances
known as colloids and as such do not possess the
power to pass through animal or vegetable mem-
branes. In a manner similar to colloids they may be
separated from their solutions by suitable treatment
with salts, such as sodium chloride, ammonium sul-
phate, etc. By a process known as "coagulation,"
which may be induced by the action of heat or the
long continued influence of alcohol the proteins lose
their colloidal characteristics which cannot be restored.

Many proteins are capable of crystallization and
indeed may occur in nature in crystalline form. It
has been found possible also to cause some to crys-
tallize although their presence in nature as crystals
is unknown. Some doubt has been cast upon the


probability of proteins, as we differentiate them at
present, being chemical units, but since many of the
crystalline plant proteins show a constancy of proper-
ties and ultimate composition there is little reason
for the assumption that these at least are mixtures of
two or more individuals.

Concerning the size of the protein molecule some
idea may be gained when it is recalled that the molec-
ular weight has been calculated to be approximately

The proteins possess the property of turning the
plane of polarized light to the left, the degree of rota-
tion for an individual protein varying with the solvent


At present proteins are classified according to their
physical properties, as, for example, their solubility
in pure water, weak salt solutions and dilute acids and
alkalies. It is well recognized that such a classifi-
cation is far from ideal, but it is the most satisfactory
plan that has been offered. When more complete
knowledge is gained concerning the chemical make-up
of the protein molecule a classification will undoubt-
edly be framed which will be based upon the presence
or proportion of certain chemical groups in the differ-
ent proteins.

All albuminous substances may be divided into


three large groups, namely, the Simple Proteins, the
Conjugated Proteins and the Derived Proteins.
Simple Proteins may be defined as substances which
yield only a-amino acids or their derivatives on hydrol-
ysis. Conjugated Proteins are substances which con-
tain the protein molecule united to some other mole-
cule or molecules otherwise than as a salt. As their
name implies, the Derived Proteins are substances that
have been formed from naturally occurring proteins.
The various sub-divisions of these large groups, as
adopted by the American Physiological Society and
the American Society of Biological Chemists, follow:

Simple Proteins Conjugated Proteins

1. Albumins. 1. Nucleoproteins.

2. Globulins. 2. Glucoproteins.

3. Glutelins. 3. Phosphoproteins.

4. Alcohol-Soluble Proteins. 4. Hemoglobins.

5. Albuminoids. 5. Lecithoproteins.

6. Histones.

7. Protamines.

Derived Proteins

A. Primary B. Secondary

Protein Derivatives. Protein Derivatives.

1. Proteans. 1. Proteoses.

2. Metaproteins. 2. Peptones.

3. Coagulated Proteins. 3. Peptides.



A. Simple Proteins

Albumins are simple proteins that are soluble in
pure water and are coagulable by heat. Globulins,
on the other hand, are insoluble in pure water but
are readily soluble in dilute salt solutions. Albumins
and globulins are generally found together in nature
occurring, for example, in large quantity in the blood
serum, white of egg, in the substance of cells in gen-
eral, and in various seeds. Egg white may be divided
into two parts by dialysis against distilled water
the globulin being precipitated owing to the diffusion
of the salts from the solution which originally were
present in quantity sufficient to hold the globulin in

Glutelins are simple proteins insoluble in all neu-
tral solvents but easily soluble in very dilute acids and
alkalies. Alcohol-Soluble Proteins are simple proteins
readily soluble in relatively strong alcohol (70 to 80
per cent), but are insoluble in water, absolute alco-
hol and other neutral solvents. These two groups of
proteins occur together as constituents of the cereal
grains. Glutenin and Gliadin, respectively, from
wheat, are the best known examples of these two
groups. They constitute the gluten of flour. The
elasticity and strength of the gluten, and therefore the


baking qualities of a flour are influenced by the pro-
portions of glutenin and gliadin.

Albuminoids may be defined as simple proteins
which possess essentially the same chemical compo-
sition as the other proteins, but are characterized by
great insolubility in all neutral solvents. Examples
of this group may be found as the organic basis of
bone (ossein), of tendon (collagen and its hydration
product, gelatin), of ligament (elastin) and of nails,
hairs, horns, hoofs, and feathers (keratins).

Histones are basic proteins which may be looked
upon as standing between protamines and the more
complex proteins. They are precipitated by other
proteins and yield a coagulum on heating which is
readily soluble in very dilute acids. The histones are
soluble in water but insoluble in ammonia. They have
been isolated from varied sources, as globin from
hemoglobin, scombron from spermatozoa of the mack-
erel, gaduhiston from the codfish and arbacin from
the sea-urchin.

Protqnines are the simplest natural proteins. They
are soluble in water, are not coagulable by heat, have
the property of precipitating other proteins from their
solutions, are strongly basic and form stable salts with
strong mineral acids. Examples of protamines are
salmin (from the spermatozoa of the salmon), sturin
(from the sturgeon), clupein (from the herring), and
scombin (from the mackerel).


B. Conjugated Proteins

Nucleoproteins are compounds of one or more
protein molecules united with nucleic acid. The
nucleoproteins, as their name implies, are the proteins
of cell nuclei and give to the latter their character.
The nucleoproteins are therefore found in largest
quantity wherever cellular material is abundant, as
in glandular tissues and organs. By artificial hydroly-
sis or during treatment in the alimentary tract a nucleo-
protein is decomposed into protein and nucleic acid.
Nucleic acid, of which there are several types, may
be made to yield a series of well-defined compounds,
the purine bases (xanthine, hypoxanthine, adenine and
guanine), the pyrimidine bases (uracile, cytosine and
thymine), a carbohydrate group (pentose or hexose)
and phosphoric acid.

Gluco proteins are compounds of the protein mole-
cule with a substance or substances containing a car-
bohydrate group other than a nucleic acid, Particu-
larly rich in glucoproteins are the mucus-yielding
portions of tissues. They serve also as a cement sub-
stance in holding together the fibers in tendons and
ligaments. An ammo-sugar, glucosamine, has been
isolated from some of the glucoproteins and it is gen-
erally regarded as constituting the carbohydrate radicle
of these conjugated proteins.

Phosphoproteins are compounds of the protein
molecule with some, as yet undefined, phosphorus-
containing, group other than a nucleic acid or lecithin.


Conspicuous foods containing phosphoproteins are
milk with its caseinogen and egg yolk with its vitellin.
A trace of iron is also evident in these proteins and
although it is possibly present as an impurity there
is no evidence that it does not exist in combination
with the protein.

Hemoglobins are compounds of the protein mole-
cule with hematin or some similar substance. The
coloring matter of the blood is hemoglobin which
acts as oxygen carrier for the tissues and is charac-
terized by holding iron as a constituent part in organic
combination. Globin is the protein portion of hemo-
globin. In certain of the lower animal forms copper
enters into combination with protein forming haemo-
cyanin imparting a blue color to the blood.

Lecitho proteins are compounds of the protein mole-
cule with lecithins. Lecithins are complexes charac-
terized by yielding glycerol, phosphoric acid, fatty
acid radicles, and a nitrogenous base, choline. The
lecithins are present in all plant and animal cells but
are especially abundant in the nervous tissues. They
belong to the group of essential cell constituents.

C. Derived Proteins

Certain of the native soluble proteins upon con-
tinued contact with water, or the influence of enzymes
or acid change their character and become insoluble.
Such insoluble substances are called proteans. After
repeated reprecipitation globulins may become insolu-


ble, that is, they are changed to proteans, and it is
believed by some protein investigators that nearly
every protein may assume a protean state.

The metaproteins may be formed from simple
protein by the action of acids and alkalies. In this
instance, however, the change is undoubtedly more
profound than in the case of the proteans. Formerly,
metaproteins were termed albuminates, that formed
by acid being called acid albuminate, that from the
action of alkali being designated alkali albuminate.
These substances are insoluble in neutral fluids but
are readily soluble in an excess of acid or alkali. The
metaproteins are of interest when it is recalled that
the acid metaprotein arises as the first step in gastric
digestion of protein and that likewise alkali meta-
protein may be formed during pancreatic digestion.

The coagulated proteins can be produced from
simple proteins by the long continued action of alco-
hol, stirring or shaking of their solutions, or by the
influence of heat. In one instance, namely, the trans-
formation of fibrinogen into fibrin in shed blood, the
process has long been assumed to be induced by an
enzyme. More recent work, however, tends to show
that enzyme action is not concerned in the reaction.

The class of derived proteins called Secondary
Protein Derivatives represent a more profound change
from simple proteins than is true for the proteans,
metaproteins and coagulated proteins which are
grouped together as Primary Protein Derivatives.
Of the secondary protein derivatives the proteases


and peptones are characterized chiefly by their greater
solubility and by the fact that, unlike most other pro-
teins, they are diffusible through suitable membranes.
They represent stages in gastric, pancreatic and bac-
terial digestions of protein and the peptones are
regarded as products of greater cleavage than the
proteoses. There are several proteoses, as protopro-
teose, heteroproteose and deuteroproteose and prob-
ably there may be several types of peptones. The
proteoses are distinguished from the peptones prin-
cipally in being precipitated from solutions by satura-
tion with ammonium or zinc sulphate.

The peptides are "definitely characterized combina-
tions of two or more amino acids, the carboxyl
(COOH) group of one being united with the amino
(NH 2 ) group of the other with the elimination of a
molecule of water." For example, if two molecules
of glycocoll (glycine) amino-acetic acid are con-
densed, a peptide, glycyl-glycine, will result. Thus







CH 9 . COOH glycyl-glycine .

The peptides are designated di-tri-tetra-peptides, etc.,
according to the number of amino acids in combina-
tion. The name polypeptides is also applied to these


substances. It is usually accepted at the present time
that the peptones are relatively simple polypeptides,
the line of demarcation between a simple peptone and
a complex peptide not being well defined.


For nearly a century chemists have been seeking
to establish the composition and structure of the pro-
tein molecule. Progress, which was slow and irregular
in the earlier decades of this period, has taken rapid
strides in the last twenty years, more intimate knowl-
edge of the problem being gained during this inter-
val than in all previous time. The investigation has
been pursued in three directions first the demolition
of the molecule and the subsequent identification of
the resulting fragments; second, the determination of
the quantitative relationships of these fragments ; and
finally, attempts to unite the disintegration products
in such a manner as to reproduce the original molecule.

After a considerable period of investigation it was
established that, although the protein molecule may
yield different types of substances according to the
character of the means employed for disrupting it
thus indicating a variety of possible lines of cleavage,
hydrolysis furnishes the most promising types of
units. Latterly, this type of chemical reaction has
been employed exclusively and it has yielded the
important information now available concerning the
nature of the protein decomposition products. Each


protein investigated by this method was found to
yield relatively large molecules, such as proteoses and
peptones, and on further disintegration a series of
comparatively simple nitrogenous substances of low
molecular weight which belong to a definite group of
chemical compounds namely, the amino acids. An
amino acid may be regarded as an organic acid in
which one hydrogen is replaced by the amino group
(NH 2 ), or viewed from another standpoint, an
amino acid may be considered as a substituted am-
monia, one hydrogen of ammonia, NH 3 , being
replaced by an organic acid. A description of the
amino acids yielded by proteins follows.

Glycocoll or glycine, amino-acetic acid. CH2. < rnnw
is the simplest of the products obtained from pro-
tein by hydrolytic cleavage and it was also the first to be
discovered. Its separation dates back to 1820 in which
year Braconnot obtained the substance by boiling gelatin with
sulphuric acid, and because of its sweet taste called it sugar
of gelatin. About twenty-five years later Dessaignes isolated
it after a hydrolysis of hippuric acid. It was shown by
Strecher in 1848 that glycocholic acid, then called cholic acid,
consists of a combination of cholalic acid and glycocoll, and
in consequence of its being a constituent of a bile acid, glyco-
coll assumed a position of some physiological importance. Its
presence in various types of albuminoids, such as elastin, etc.,
was later demonstrated and finally it was shown to be a
decomposition product of globulin. Glycocoll is not present
in all proteins for albumin, casein, and hemoglobin fail to
yield it, and from the vegetable proteins it is obtained in
small quantities only. On the other hand, albuminoids are
particularly rich in glycocoll. In an extract of the mollusc


Pecten irradians Chittenden found glycocoll in a free state;
and it has been reported as occurring in the urine under vari-
ous pathological conditions. After administration of benzoic
acid to man and animals hippuric acid (benzoyl-glycocoll) is
found in the urine thus demonstrating a synthesis of hip-
puric acid from benzoic acid and glycocoll. J>

Alanine a-amino-propionic acid. CHa.CH <
was prepared synthetically previous to its isolation
from among the protein decomposition products and was
named by its discoverer, Strecher. Alanine has been shown
to be a constant decomposition product of proteins.

Valine a.-amino-isovalerianic acid. >CH.CH<

In 1856 v. Gorup-Besanez isolated a substance having the
formula CsHnNC^ from pancreas and because it possessed
properties similar to leucine he looked upon it as a homologue
of leucine and called it butalanine. Although a similar sub-
stance was isolated from certain seedlings by Schulze and
Barbieri, and from the protamine, clupeine, by Kossel, it was
not until 1906 that its identity was established by Fischer
who gave it the name of valine. Valine is obtained from most

Leucine. a-amino-isobutylacetic acid.


Leucine was described by Proust in 1818 and was called
oxide-caseux. Braconnot in 1820 obtained a substance from a
hydrolysis of meat which on account of its glistening white
appearance he called leucine. Liebig regarded it as one of the
constituents of the protein molecule and this was later proved
to be correct. Leucine is also a constituent of many organs
and tissues occurring in the free state. It is yielded by both


animal and vegetable proteins and with the possible exception
of arginine is the most widely distributed amino acid found as
a protein cleavage product. Leucine has been found also in
the urine under pathological conditions.
Isoleucine. a-amino-/3-ethyl-propionic acid.

NH 2

This amino acid was not described as a protein constituent
until 1903 when it was isolated as a decomposition product of
fibrin and other proteins by F. Ehrlich.

Norleucine. a-amino-normal-caproic acid. CHs.CEb.
CH2.CH2.CH.NH2.COOH. From the leucine fraction of
the decomposition of the proteins of nervous tissue this amino
acid has recently been isolated by Abderhalden and Weil. It
is probable that other proteins may yield it also.

Phenylalanine -. /3-phenyl-a-amino-propionic acid.


Although it had been recognized for many years that a
substance having the composition of CgHnNC^ could be ob-
tained by cleavage of both animal and vegetable proteins, -it
was Fischer who first proved the presence of phenylalanine as
a protein derivative. In those proteins lacking tyrosine, as
gelatin, for example, the aromatic ring is supplied by phenyla-

Tyrosine. /3-para-oxyphenyl-a-amino-propionic acid.


In 1846 Liebig isolated from a decomposition of cheese a
substance possessing the property of crystallizing in silky
needles. He named it tyrosine. Since then tyrosine has been
regarded as a protein cleavage product. It was not until 1882,


however, that the structure of tyrosine was positively deter-
mined. Tyrosine is absent from the gelatine molecule. In
acute yellow atrophy of the liver and in phosphorus poisoning
it is claimed that tyrosine may be present as a urinary con-
Serine /3-hydroxy-a-amino-propionic acid.

Cramer found serine among the decomposition products of
sericin (silk gelatin), and it was not obtained again until 1902

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Online LibraryFrank Pell UnderhillThe physiology of the amino acids → online text (page 1 of 10)