ABSORPTION, ASSIMILATION, AND THE PROCESSES OF METABOLISM
TOPICS: Physiological peculiarities in absorption. Chemical changes
in epithelial walls of intestine. Two pathways for absorbed
material. Function of the liver as a regulator of carbohydrate.
Absorption of proteid products. Assimilation of food products.
Anabolism. Katabolism. Metabolism. Processes of metabolism. Older
views regarding oxidation. Discoveries of Lavoisier. The views of
Liebig. Theory of luxus consumption. Oxidation in the body not simple
combustion. Oxygen not the _cause_ of the decompositions. Oxidation
not confined to any one place. Intracellular enzymes. Living cells
the guiding power in katabolism. Some intermediary products of tissue
metabolism. Chemical structure of different proteids. Decomposition
products of nucleoproteids. Relation to uric acid. Action of specific
intracellular enzymes. Creatin and creatinin. Relation to urea.
Proteid katabolism a series of progressive chemical decompositions.
Intracellular enzymes as the active agents.
Digestion being completed, and the available portion of the foodstuffs
thereby converted into forms suitable for absorption, the question
naturally arises, In what manner are these products transported
from the alimentary tract to the tissues and organs of the body? In
attempting to answer this question, we shall find many illustrations
of the precise and undeviating methods which prevail in the processes
of nutrition. For example, it would seem plausible to assume that the
different forms of sugar entering into man’s ordinary diet, all of
them being soluble, would be directly absorbed and at once utilized,
but such is far from being the case. Milk-sugar and cane-sugar, both
appearing in greater or less degree in our daily dietaries, if
introduced directly into the blood, are at once excreted through the
kidneys unchanged. The body cannot use them, and they are gotten rid
of as speedily as possible, much as if they were poisons. When taken
by way of the mouth, however, they are utilized, simply because in
the intestine two enzymes are present there, known as lactase and
invertase, which break each of the sugars apart into two smaller
molecules. In other words, milk-sugar and cane-sugar are disaccharides,
and if they are to be absorbed in forms capable of being made use
of by the body they must be split apart into simpler sugars, viz.,
monosaccharides, such as dextrose, levulose, etc. The great bulk of the
carbohydrate food consumed by man is in the form of starch, and this,
as we have seen, is converted into maltose by the action of saliva and
pancreatic juice. Maltose, however, like cane-sugar, is a disaccharide,
and the body has no power to burn it or utilize it directly; but in the
intestine and elsewhere is an enzyme termed maltase, which breaks up
maltose into two molecules of the monosaccharide dextrose, and this the
body can use. Man frequently consumes starch to the extent of a pound a
day, and if utilized it must all undergo transformation into maltose,
and then into dextrose. There is no apparent reason why maltose should
not be absorbed and assimilated as readily as dextrose, but so urgent
is the necessity for this conversion into dextrose that in the blood
itself there is present maltase, to effect the transformation of any
maltose that may gain entrance there. We are here face to face with
a simple fact in nutrition. The body cannot utilize disaccharides
directly. Why it is so we cannot say, but the fact is a good
illustration of the principle that nothing can be taken for granted in
our study of nutrition.
For years, physiologists assumed that the ordinary physical laws of
osmosis, imbibition, and diffusion were quite adequate to explain
the passage of digested food materials into the blood and lymph.
If a substance was soluble and diffusible, that was sufficient; it
would quite naturally be absorbed in harmony with its diffusion
velocity. This, however, is not wholly true, since experiment shows
that the rapidity of absorption of diffusible substances through
the wall of the intestine is by no means always proportional to the
diffusion velocity of the substance. The lining membrane of the
small intestine, where absorption mainly takes place, is not to be
compared to a dead parchment membrane. On the contrary, it is made
up of living protoplasmic cells; absorption is not a physical, but a
physiological, process, in which the living epithelium cells stand as
guardians of the portals, ready to challenge and, if need be, modify
the rate of passage. Osmosis and diffusion undoubtedly play some part
in absorption, but they alone are not sufficient to account for what
actually takes place in the absorption of digestion products, and other
substances from the living intestine.
The primary products formed in the digestion of proteid foods--the
proteoses and peptones--afford another illustration of physiological
peculiarity in absorption. These bodies are readily soluble and
quite diffusible, yet they are never found to any extent in the
circulating blood and lymph during health. It is of course possible,
as has been previously suggested, that as soon as formed they undergo
transformation into simpler decomposition products in the small
intestine; but this is by no means certain. If proteoses and peptones
are injected directly into the blood, they cause a marked disturbance,
influencing at once blood-pressure, affecting the coagulability of
the blood, and in many other ways exhibiting a pronounced deleterious
action which at once indicates they are out of their normal
environment. They are not at home in the circulating blood, and the
latter medium gets rid of them as speedily as possible; they behave
like veritable poisons, and yet they are the primary products formed
in the digestion of all proteid foodstuffs. On the basis of all
physical laws governing diffusion they should be absorbed, and help to
renew the proteids of the blood and later the proteids of the tissues.
Yet, as we have said, they are not normally present in the blood or
lymph. Apparently, in the very act of absorption, as they pass through
the epithelial cells of the intestinal wall, before they gain entrance
to the blood stream, they undergo transformation into serum-albumin
and globulin, the characteristic blood proteids. The other alternative
is that, as previously mentioned, they are completely broken down
in the intestine into amino-acids, etc., and these simpler products
synthesized, as they pass through the intestinal wall toward the blood,
into serum-albumin and globulin. Certainly as yet, there is no evidence
that the amino-acids, as such, go through the epithelial cells of the
intestine; they are not found in the blood or lymph to any appreciable
extent, yet the proteids of the blood are reinforced in some manner by
the products of proteid digestion. Whichever view is correct, one thing
is perfectly obvious, viz., that in the act of absorption the products
resulting from the gastric and pancreatic digestion of proteid foods
are exposed to some influence, presumably in the epithelial cells of
the intestinal wall, by which there is a reconstruction of proteid.
Further, the proteid substances so formed are of the type peculiar to
the blood of that particular species of animal. The proteids of beef,
mutton, chicken, oatmeal, or bread go to make the proteids of human
blood.
From these statements, it is obvious that what we term absorption is
something more than a simple diffusion of soluble substances from
the alimentary tract into the blood current. The process is much
more complex than appears on the surface, and our lack of definite
knowledge, in spite of numerous efforts to unravel the mystery,
merely strengthens the view that we are dealing here with an obscure
physiological problem, and not a simple physical one. Digestion induces
a splitting up of the food proteid into fragments, large or small,
while incidental to absorption there is apparently a reconstruction,
or synthesis, of proteid from the fragments so formed. The process
seems somewhat costly, physiologically speaking, yet when one considers
the variety of proteids consumed as food, it is easy to comprehend
how essential it is that in some manner, as in absorption, there be
opportunity for construction of the specific proteids of the blood and
lymph.
We find an analogous process in the absorption of fats. As we have
seen, the fats of the food are broken apart in the small intestine into
glycerin and free fatty acid, a portion of the latter, and perhaps all,
combining with the alkali of the intestinal juices to form soluble
soaps, or sodium salts of the respective fatty acids. The neutral fats
present in animal and vegetable foods are all alike in containing
the glyceryl radicle, but they differ in the character of the fatty
acids present. Further, one form of animal fat, like that from beef,
may contain quite a different proportion of stearin, palmitin, and
olein than is present in the fat of another animal, like mutton. By
digestion, however, they are all broken apart into fatty acid and
glycerin. These acids and their salts can be readily detected in the
intestine, but they are not found in the blood or lymph, yet shortly
after fatty food is taken the lymph is seen to be milky from fat.
Obviously, the fatty acids liberated in the intestine are absorbed,
either as soluble soaps or as free fatty acids dissolved in bile, but
as they pass through the epithelial cells of the intestine into the
lacteal radicles, there is a synthesis or reconstruction of fat; and
as a result, neutral fats and not soaps are found in the lymph. Here,
then, we have a process quite analogous to what apparently occurs in
the absorption of proteid, though less complex; and it is possible that
this is one of the factors which aids in the formation of a specific
fat mixture corresponding, in a measure, to the type of fat present
in the particular species. It is well understood that the fat of an
animal’s tissues may be modified somewhat by the character of the
fat fed, yet in spite of this there is a certain degree of constancy
in composition which calls for explanation. Sheep and oxen feeding
in the same pasture have fat widely different in the proportion of
stearin, palmitin, etc. The fat of man’s tissues is fairly definite
in composition, yet he eats a great variety of fatty foods. One man
may consume large amounts of hard mutton fat with its relatively large
content of stearin, while another individual may take his fat mainly in
the form of the soft butter fats, with their relatively large content
of olein and palmitin. In both cases, the fat of the man’s tissues will
be essentially the same. To be sure, the changes that take place in the
tissue cells, reinforced by the construction of fat from other sources,
may be partly responsible for this constancy of composition, but the
transformations incidental to absorption are quite possibly, in some
measure, helpful thereto.
The great bulk of the digested food material is absorbed from the small
intestine, and there are two pathways open through which the absorbed
material can gain access to the blood. The one path leads directly to
the liver, and substances taking this course are exposed to the action
of this organ, before they enter into the general circulation. The
other path is through the lacteal or lymphatic system, and constitutes
a roundabout way for substances to enter the blood stream, since
they must first pass through the thoracic duct before entering the
main circulation. As a general truth, it may be stated that fats are
absorbed through the latter channel, while carbohydrates and proteids
follow the first path. The innumerable blood capillaries in the villi
of the intestine take up the products resulting from the digestion
of proteids and carbohydrates, through which they are passed into
the portal vein, and thereby distributed throughout the liver. This
means that both carbohydrates and proteids--or their decomposition
products--are exposed to a variety of possible changes in this large
glandular organ, before they can enter into the tissues of the body.
As we have seen, practically all carbohydrate food is converted into
a monosaccharide, principally dextrose, in the alimentary tract; and
it is in this form of a simple sugar that the carbohydrate passes into
the blood. This might easily mean a pound of sugar absorbed during
the twenty-four hours, and would obviously give to the blood a high
degree of concentration, unless the excess was quickly disposed of.
Sugar is very diffusible, and if it accumulates to any extent in the
blood it is quickly gotten rid of by excretion through the kidneys.
This, however, is wasteful, physiologically and otherwise, and does not
ordinarily occur except in diseased conditions. Further, physiologists
have learned that a certain small, but definite, amount of sugar in the
blood is a necessary requirement in nutrition, and it is the function
of the liver to maintain the proper carbohydrate level.
We must again emphasize the great importance of carbohydrate food;
there is a far larger amount of starchy food consumed than of any
other foodstuff, and it is more readily available as a source of
energy. Its presence in the blood, in the form of sugar, is constantly
demanded, but it must be kept within the proper limits for the uses
of the different tissues and organs of the body. The liver serves as
an effective regulator, maintaining, in spite of all fluctuations
in the supply and demand, a definite percentage of sugar such as is
best adapted to keep the tissues of the body in a normal and healthy
condition. This regulation by the liver is rendered possible through
the ability of the hepatic cells to transform the sugar brought to
the gland into glycogen, so-called animal starch, which is stored
up in the liver until such time as it is needed by the body. The
process is one of dehydration, the reverse of what takes place in the
intestine when ordinary starch is converted into maltose and dextrose.
The efficiency of this regulating mechanism depends also upon the
ability of the liver to transform glycogen into sugar, presumably
through the agency of an enzyme in the hepatic cells. Hence, glycogen
may be looked upon as a temporary reserve supply of carbohydrate,
manufactured and stored in the liver during digestion, when naturally
large amounts of sugar are passing into the portal blood, and to be
drawn upon whenever from any cause the content of sugar in the blood
threatens to fall below normal. Obviously, there must be some delicate
machinery for the adjustment of these opposite changes in the liver,
and we may well believe that it is associated with the composition
of the blood itself, which in some fashion stimulates and inhibits,
as may be required, the functional activity of the liver, or its
component cells. In any event, we have in this so-called glycogenic
function of the liver a most effective means for accomplishing the
complete and judicious utilization of all the sugar formed from the
carbohydrates of the food, after it has once passed beyond the confines
of the alimentary tract into the blood; preventing all loss, and at
the same time guarding against all danger, from undue accumulation
of sugar in the circulation. We see, too, how wise the provision
that all sugar should pass from the alimentary canal into the portal
circulation and not by way of the lymphatics, since by the latter
channel the regulating action of the liver would be mainly lost.
Further, recalling how soluble and diffusible sugar is, we may well
marvel that it practically all passes from the intestine by way of
the blood, and escapes entry into the lymphatics. Surely, this marked
shunning of the other equally accessible pathway affords a striking
illustration of selective action such as might be expected in a
physiological process, but not in harmony with the ordinary physical
laws of osmosis or diffusion. In conformity with this statement, it may
be mentioned that appropriate experiments have clearly demonstrated
that the different sugars available as food are not absorbed from the
intestine in harmony with their diffusion velocity, but show deviations
therefrom which can be explained only on the ground that the intestinal
wall exercises some selective action, due to the living cells composing
it. Likewise interesting in their bearing on nutrition are the
observations of Hofmeister,[13] who finds by experiments on dogs that
the assimilation limit of the different sugars shows marked variation.
Thus, dextrose, levulose, and cane-sugar have the highest assimilation,
while milk-sugar is far less easily and completely assimilated. If this
is equally true of man, it indicates that starchy foods, with their
ultimate conversion into dextrose, are to be ranked as having a high
assimilation limit, thus affording additional evidence of their high
nutritive value.
[13] Franz Hofmeister: Ueber Resorption und Assimilation der
Nährstoffe. Archiv f. d. exper. Pathol. u. Pharm., Band 25, p. 240.
In the absorption of proteid products, their passage from the intestine
by way of the portal circulation insures exposure to the action of the
hepatic cells, before they are distributed by the general circulation
throughout the body. It is only under conditions of an excessive
intake of proteid foods that their products are absorbed by way of the
lymphatics. These points are clearly established, and there is every
ground for believing that substantial reasons exist to account for
this single line of departure. Just what the liver does, however, is
uncertain. In fact, as already indicated, there is lack of definite
knowledge as to how far the proteid foods are broken down in digestion,
prior to absorption. The combined action of pepsin, trypsin, and
erepsin, if sufficiently long continued, can accomplish a complete
disruption of the proteid molecule. We are inclined to assume in a
general way that the “proteids taken as food cannot find a place in
the economy of the animal body till they have been, as it were, melted
down and recast.”[14] How far this melting down or disruption extends
in normal digestion, we do not at present know. As already stated,
neither proteoses and peptones, nor the amino-acids, are found in
the blood stream in sufficient amounts, or with that frequency, to
suggest absorption in these forms. Possibly, as some physiologists have
suggested, the amount of any of these products to be found at any one
time in a given quantity of blood is too small for certain recognition,
yet in the twenty-four hours the amount passing from intestine to
liver might be sufficiently large to equal the total proteid absorbed.
We can, however, at present only conjecture, and must rest content
with the simple statement that in the digestion of the proteid
foodstuffs, proteoses, peptones, and amino-acids are formed, and that
by transformation or total reconstruction of these products, special
types of proteid are manufactured either in the epithelial cells of
the intestinal walls during absorption, or elsewhere in the body after
absorption. If this latter is the case, the liver might readily be
regarded as a likely spot for the synthesis to occur.
[14] J. B. Leathes: Problems in Animal Metabolism. Blakiston’s Son
and Co., 1906, p. 123.
Bearing in mind what has been said regarding the production of specific
types of proteid by every species of animal, we can the more readily
conceive of a synthesis “out of fragments of the original molecules
rearranged and put together in new combinations, by processes in
which the intestine can hardly be supposed to play a part.” This,
the liver might well be assumed as capable of accomplishing, and if
we were disposed to accept this view we might use as an argument the
fact that the products of proteid digestion are taken directly to
this organ, before being cast loose in the tissues and organs of the
body. There is perhaps as good ground for assuming that a synthesis
or reconstruction of proteid takes place all over the body; that, as
suggested by Leathes, “the synthesis of proteids is a function of every
cell in the body, each one for itself, and that the material out of
which all proteids in the body are made is not proteid in any form,
but the fragments derived from proteids by hydrolysis, probably the
amido-acids, which in different combinations and different proportions
are found in all proteids, and into which they are all resolved by the
processes, autolytic or digestive, which can be carried out in every
cell in the body.” It is certainly a reasonable hypothesis, and since
we lack positive knowledge it cannot at present be disproved. All that
we can affirm in the light of established fact is that the products of
proteid digestion are absorbed from the intestine by way of the portal
circulation, and that either in their passage through the intestinal
wall, or later on in the liver or elsewhere, there is a construction of
new proteid to meet the wants of the body. The liver, indeed, may be
effective in both construction and destruction of proteid, but there is
no way of telling at present just how far it acts in either direction.
Regarding the absorption of fats, a single statement will suffice, in
addition to what has already been said. Fats gain access to the general
circulation by passing from the intestine into the lacteal radicles,
thence into the lymphatics, whence they move onward into the thoracic
duct, and from there are emptied into the great veins at the neck. A
small amount is apparently absorbed in the form of soap by the portal
circulation, but by far the larger amount of fat gains access to the
blood stream without going through the liver.
* * * * *
In these ways, the blood and lymph are continually supplied with
proteid, fat, and carbohydrate from the ingested food, and as these
fluids surround and permeate the organized elements of the tissues, the
latter are enabled to gain what they need to maintain their nutritive
balance. Living matter is essentially unstable; it is the seat of
chemical changes of various kinds, anabolic or constructive, and
katabolic or destructive. The more comprehensive term “metabolic” is
applied to all of these changes that take place in living matter. In
anabolism, the dead, inert proteids, fats, and carbohydrates are more
or less assimilated and made a part of the living matter of the tissue
cells, while at the same time a certain amount of the food material,
probably the larger amount, is simply stored as such, or left to
circulate in the blood and lymph, without being raised to the higher
level of living protoplasm. In katabolism, this accumulated material,
and in some degree the living substance itself, is broken down or
disintegrated with liberation of the stored-up energy, which manifests
itself in the form of heat and mechanical work. At times, the anabolic
processes predominate and there is a relatively large accumulation
of stored-up materials; while at other times, katabolism, with its
attendant chemical decompositions, predominates, and the body loses
correspondingly. The point to be emphasized here is that the living
body, with its multitude of living cells, is the seat of incessant
change. Construction and destruction are continually going forward
side by side; sometimes the one and sometimes the other predominating,
according to existing conditions. The living protoplasm with its
attendant storage material is, under ordinary conditions, constantly
being made good from the assimilated food, a part of which is raised to
the dignity of living matter and becomes an integral part of the living
cells, while the larger portion is simply stored for future uses, or
circulates in the blood and lymph which bathe them. Doubtless, this
storage or circulating material is the main source of the energy which
constantly flows from the cells in the form of heat and of work, as a
result of the disruptive changes that constitute katabolism.
Worthy of special notice is the fact that cell protoplasm is
essentially proteid in nature; water and proteid make up the larger
part of its substance, to which are added small proportions of
carbohydrate, fat, and mineral matter. Proteid is the basis of cell
protoplasm; it is the chemical nucleus of living matter, and owing to
the large size of its molecule, with its large number of contained
atoms, is capable of many combinations and many alterations. Most of
the reactions characteristic of katabolism centre around this proteid,
but the disruptive changes that occur undoubtedly involve more largely
the circulating materials present in the blood and lymph, and which
bathe the cells, rather than the so-called fixed, or organ proteid, of
the cell substance itself. Still, while the circulating blood and lymph
furnish largely the substances which are made to undergo disintegration
in katabolism, the living protoplasmic cell is the controlling power
which regulates the extent and character of the decompositions,
and proteid matter is the chemical basis of protoplasm. From these
statements, we again have suggested the significant importance of the
proteid foods in nutrition, since they alone can furnish the material
which constitutes the chemical basis of living cells. The human body,
which represents the highest form of animal life, is merely, as stated
by another, “literally a nation of cells derived from a single cell
called the ovum, living together, but dividing the work, transformed
variously into tissues and organs, and variously surrounded by
protoplasm products” (Waller).
The processes involved in metabolism are not easily unravelled. The
word itself is simple, but it is employed to designate that complex of
“chemical changes in living organisms which constitute their life, the
changes by which their food is assimilated and becomes part of them,
the changes which it undergoes while it shares their life, and finally
those by which it is returned to the condition of inanimate matter.
Gathered together under this one phrase are some of the most intricate
and inaccessible of natural phenomena. It implies also, and gently
insists on the idea, that all the phenomena of life are at bottom
chemical reactions” (Leathes). Regarding the processes of anabolism, as
in the construction of living protoplasm out of inert food materials,
we can say nothing. This is altogether beyond our ken at present, and
doubtless will remain so, since it involves a chemical alteration, or
change, akin to that of bringing the dead to life. With the processes
of katabolism, however, we may hope for more satisfactory results; and,
indeed, to-day we have considerable information of value as to some of
the methods, at least, which are the cause of this phase of nutrition.
This knowledge, however, has been slow of attainment.
In the earlier years of the sixteenth century, when anatomy and
physiology were beginning to make progress, the savants of that day,
hampered as they were by grave misconceptions and by the lack of
any understanding of chemical phenomena, could not take advantage,
naturally, of the suggestion that as wood burns or oxidizes in the air
with liberation of heat, so might the food substances, absorbed by the
body, undergo oxidation in the tissues and thus give rise to animal
heat. Such suggestions were at that time as a closed book, and so we
find Vesalius, in 1543, teaching the Galenic doctrines in physiology
then prevalent. The conception of heat production, as it existed at
that time, may be inferred from the following quotation:[15] “The parts
of the food absorbed from the alimentary canal are carried by the
portal blood to the liver, and by the influence of that great organ
are converted into blood. The blood thus enriched by the food is by
the same great organ endued with the nutritive properties summed up
in the phrase ‘natural spirits.’ But blood thus endowed with natural
spirits is still crude blood, unfitted for the higher purposes of the
blood in the body. Carried from the liver by the vena cava to the right
side of the heart, some of it passes from the right ventricle through
innumerable invisible pores in the septum to the left ventricle. As the
heart expands it draws from the lungs through the vein-like artery air
into the left ventricle. And in that left cavity, the blood which has
come through the septum is mixed with the air thus drawn in, and by the
help of that heat, which is innate in the heart, which was placed there
as the source of the heat of the body by God in the beginning of life,
and which remains there until death, is imbued with further qualities,
is laden with ‘vital spirits,’ and so fitted for its higher duties. The
air thus drawn into the left heart by the pulmonary vein, at the same
time tempers the innate heat of the heart and prevents it from becoming
excessive.” In other words, heat was considered as a divine gift, and
as can readily be seen, there was an utter lack of appreciation of the
use of air in breathing. Even van Helmont, who lived in 1577–1644, and
was in a sense an alchemist, still gave credence to the spirits, viz.,
that the food absorbed from the stomach and intestine is in the liver
endued with natural spirits, while in the heart the natural spirits
are converted into vital spirits, and in the brain the vital spirits
are transformed into animal spirits.[16] Later, Malpighi discovered
the true structure of the lungs, and Borelli, in 1680, exposed the
erroneous views then prevalent regarding the purpose of breathing.
It is not true, says Borelli, that the use of breathing is to cool
the excessive heat of the heart or to ventilate the vital flame, but
we must believe that this great machinery of the lungs, with their
accompanying blood vessels, is for some grand purpose. In a long and
vigorous argument, he contends that the “air taken in by breathing is
the chief cause of the life of animals, far more essential than the
working of the heart and the circulation of the blood.” He quotes the
experiments of Boyle, who showed in 1660 “that even in a partial vacuum
brought about by his air pump, flame was extinguished and life soon
came to an end; the candle went out and the mouse or the sparrow died.”
[15] Taken from Sir Michael Foster’s “Lectures on the History
of Physiology during the Sixteenth, Seventeenth, and Eighteenth
Centuries.” Cambridge, 1901, p. 12.
[16] See Foster’s Lectures, p. 136.
At this time, and for long afterwards, the belief was prevalent
that the air taken up by the blood in the lungs was the air of the
atmosphere in its entirety. No one appears to have thought of the
possibility of only a part of the air being used, for at that time
there was no suspicion that air was a mixture of substances. Mayow,
however, in 1668, showed that it was not the whole air which was
employed for respiration, but a particular part only. At this time,
great attention was being given to a study of nitre or saltpetre; its
wonderful properties in combustion were being recognized, and Mayow,
who was a chemist of repute, claimed that it had its origin partly
in the air and partly in the earth. The air “which surrounds us, and
which, since by its tenuity escapes the sharpness of our eyes, seems
to those who think about it to be an empty space, is impregnated
with a certain universal salt, of a nitro-saline nature, that is to
say, with a vital, fiery, and in the highest degree fermentative
spirit,” to which the name of “igneo-aereus” was applied. Nitre was
shown to be composed of a _sal fixum_ or sal alkali,--potash as it
is now called,--and was obviously derived from the earth, while the
other part of nitre was made up of the _spiritus acidus_, or nitric
acid. For a time it was supposed that the whole of this _spiritus
acidus_ was contained in the atmosphere, but it was soon recognized
that this could not be the case, since nitric acid was found to be a
corrosive liquid, destructive to life and quite incapable of supporting
combustion. Hence, Mayow concluded that only a part of the acid
exists in the atmosphere, viz., that part which he termed _spiritus
nitro-aereus_. In combustion, there is something in the air which is
necessary for the burning of every flame, unless perchance igneo-aereal
particles should pre-exist in the thing to be burnt. These igneo-aereal
particles form “the more active and subtle part of air which is thus
necessary for combustion, exist in nitre and indeed constitute its
‘more active and fiery part.’” Mayow fully recognized that burning
and breathing involved in a measure the same process; both consisted
in the consumption of the igneo-aereal particles present in the air.
“If a small animal and a lighted candle be shut up in the same vessel,
the entrance into which of air from without be prevented, you will see
in a short time the candle go out, nor will the animal long survive
its funeral torch. Indeed, [says Mayow] I have found by observation
that an animal shut up in a flask together with a candle will continue
to breathe for not much more than half the time than it otherwise
would, that is, without the candle.” Something contained in the air,
necessary alike for supporting combustion and for sustaining life,
passes from the air into the blood. Mayow expressed his thoughts in
these words: “And indeed it is very probable that certain particles
of a nitro-saline nature, and those very subtle, nimble, and of very
great fermentative power, are separated from the air by the aid of the
lungs and introduced into the mass of the blood. And so necessary for
life of every kind is that aereal salt (constituent) that not even
plants can grow in earth the access of air to which is shut off. But
if that same earth be exposed to air and so forthwith impregnated with
that fecundating salt, it at once becomes fit again for growing.”[17]
Mayow fully appreciated the importance of his nitro-aereal particles in
the processes of life; he had indeed a fairly accurate conception of a
sound theory of animal heat; he saw that they were equally necessary
for burning, or combustion, and for respiration, and so was enabled to
draw a parallelism between the two processes; he pointed out that they
were essential for the ordinary activity of the muscles of the body,
that as muscle work was increased more particles from the air were
required; indeed, he clearly foresaw the need which the body had for
these igneo-aereal particles in all the chemical processes of life. And
thus was foreshadowed a conception of oxidation, a hundred years before
Priestley evolved his phlogiston theories and Lavoisier discovered
oxygen.
[17] Quoted from Foster’s Lectures, p. 195.
The discoveries of Lavoisier, published in 1789, led to a clear
understanding of combustion as a process of oxidation, and paved the
way for a fuller knowledge of the part played by the oxygen of the
air in the chemical reactions going on in the animal body. Lavoisier
showed that the oxygen drawn into the lungs with the air breathed was
used in the body for the oxidation of certain substances, carbon being
transformed thereby into carbon dioxide, and hydrogen into water.
Further, he noted that these oxidations were carried forward on a
large scale, and he emphasized the importance of oxygen as being the
true cause of the varied decompositions taking place in the living
body. The larger the amount of oxygen inspired, the more extensive
the oxidation, and consequently the rate of respiration as modifying
the intake of oxygen served in his opinion as a regulator to control
the extent of the oxidative processes. He pointed out that a definite
relationship existed between the amount of work done by the body and
the oxygen consumed; greater muscular activity, lower temperature of
the surrounding air, the activities attending the digestive functions,
all seemed to be associated with a greater utilization of oxygen.
Oxidation was the pivot around which all the chemical reactions of the
body seemed to centre. Lavoisier, however, was not a physiologist, and
he was, quite naturally perhaps, led into some errors. For example,
he considered that the process of combustion or oxidation took place
in the lungs, certain fluids rich in carbon and hydrogen formed in
the different organs of the body being brought there for exposure to
the inspired oxygen. Further, his views implied a simple and complete
combustion, in which complex substances rich in carbon were directly
and completely oxidized to carbon dioxide and water, in much the same
manner as combustion occurs outside the body. Again, he assumed that
the amount of oxygen taken into the lungs determined the extent of
oxidation, just as the use of the bellows, by increasing the draft of
air, causes the fire to burn more brightly.
To Liebig (1842) the next great advance was due. This phenomenally
clear-minded man, while recognizing at their full value the fundamental
theories advanced by Lavoisier, saw and fully appreciated their
incompleteness, and he likewise understood their failure to explain
many of the phenomena of life more familiar to the physiological mind
than to that of a simple chemist like Lavoisier. Liebig had made a
special study of the chemical composition of foodstuffs, and likewise
of the tissues and organs of the body. He had, moreover, given great
attention to the decomposition products formed in the body, especially
the nitrogenous substances excreted through the kidneys, as well as the
carbon dioxide and water passed out through the lungs and skin. It was
not strange, therefore, that he should take exception to Lavoisier’s
view that oxidation in the body consisted in the combustion of a
fluid, rich in carbon and hydrogen, which was brought to the lungs.
On the contrary, Liebig contended that it was the organic compounds,
proteids, fats, and carbohydrates, that underwent oxidation, and not
necessarily in the lungs, but all over the body, wherever organs and
tissues were active. Especially noteworthy was the view advanced by
Liebig, and upheld for many years, that of these three classes of
compounds the proteids alone served for the construction of organized
tissues, like muscle, and that in the activity of this tissue, as
in muscle contraction or muscle work, the energy for the work was
derived solely from the breaking down or oxidation of this organized
proteid. On this ground he termed the proteid foodstuffs “plastic,” or
tissue-building foods. Liebig further pointed out that the substances
of the body have the power of combining with and holding on to the
inspired oxygen, and that fats and carbohydrates, _i. e._, the
non-nitrogenous compounds, easily undergo oxidation or combustion, and
thereby furnish the heat of the body. For this reason he termed the
corresponding foodstuffs “respiratory” foods. Proteids, on the other
hand, according to Liebig’s view, are capable of combustion only in
slight degree. The cause of the decomposition of proteid substances in
the body was to be traced solely to muscle work, _i. e._, the energy
of muscle contraction, or muscle work, was derived from the breaking
down of the proteids of the muscle tissue, and work was the stimulus
which brought about proteid decomposition. Non-nitrogenous substances
played no part in these reactions; muscle work was without influence
on these compounds, oxygen being the sole stimulus which led to their
combustion, and heat was the sole product of the combustion.
If Liebig’s theory is correct, that the proteids of the body are
decomposed only as the result or the accompaniment of muscle work, and
the proteids of the food are used up only as they take the place of the
organized proteid so metabolized, it follows that with a like degree of
muscular activity a given body will always decompose the same amount
of proteid. If excess of proteid food is taken, the surplus will be
stored in the tissues, or, in other words, the excretion of nitrogen
will not be influenced by the amount of proteid consumed in the food.
This was the line of argument made use of by various physiologists[18]
who were disposed to criticise Liebig’s view, and quite naturally the
question was soon made the subject of many experiments. It will suffice
here merely to say that many concordant results were obtained, showing
that an abundance of proteid food leads to an increase in the excretion
of nitrogen, muscle activity remaining at a constant level. Hence, as
Voit states, some other ground than muscle work must be sought as the
true cause of proteid katabolism. Consequently, we find this hypothesis
of Liebig replaced by the theory of “luxus consumption,” in which it
is maintained that while whatever proteid is used up by the work of
the muscle must be made good from the proteid of the food, any excess
of proteid absorbed from the intestinal canal is to be considered as
“luxus,” and like the non-nitrogenous foods may be burned up in the
blood, by the oxygen therein, without being previously organized.
Hence, we see suggested two causes for the decomposition of proteid in
the body, viz., the work of the muscle and the oxygen of the blood.
Further, as stated by C. Voit,[19] the nitrogen excretion of the hungry
or fasting animal affords, according to these views, a measure of the
extent to which tissue proteid must be broken down in the maintenance
of life, and of the amount of proteid food necessary to be consumed in
order to make good the loss; viz., the minimum proteid requirement.
Again, since any excess of proteid food beyond this minimal
requirement, according to the theory, is destined to be burned up in
the blood, or elsewhere, to furnish heat the same as non-nitrogenous
foods, it follows that the excess of proteid food can be replaced by
non-nitrogenous aliment.
[18] See C. Voit: Hermann’s Handbuch der physiologie des
Gesammt-Stoffwechsels. Band 6, Theil 1, p. 269, 1881.
[19] Loc. cit., p. 270.
Oxidation, however, is the keynote in any explanation of the processes
of metabolism, whether nitrogenous or non-nitrogenous matter is
involved. Both alike undergo oxidation, but it is not simple oxidation
or combustion that we have to deal with. In the time of Lavoisier, as
already stated, it was thought that oxygen alone was the cause of the
decomposition going on in the body, but simply increasing the intake
of air or oxygen, as in quickened breathing or deeper inspiration,
does not increase correspondingly the rate of oxidation. In other
words, it is not a direct combination of oxygen with the carbon and
hydrogen of the foodstuffs, or tissue elements, that takes place in
the body, but rather a gradual, progressive decomposition of complex
organic compounds into simpler products; made possible, however, by the
agency of the oxygen carried from the lungs by the circulating blood.
It was demonstrated years ago that animals breathing pure oxygen do
not consume any more of the gas than when breathing ordinary air, and
likewise no more carbon dioxide is produced in the one case than in
the other. Fifty years ago, Liebig and other physiologists showed that
frogs’ muscle placed in an atmosphere free of oxygen could be made to
contract or do work for some considerable time, and with liberation
of heat. This fact implies a breaking down of muscle substance into
simpler bodies, but there is here no free oxygen to act as the inciting
cause; indeed, what actually occurs is a cleavage or splitting up
of substances in the muscle tissue, but at the expense of oxygen in
some form of combination in the muscle. This oxygen must have been
taken from the blood at some previous time and stored in the tissue
for future use. Again, as C. Voit has expressed it, if oxygen were
really the immediate cause of the decompositions taking place in the
organism, we should expect combustion to occur in harmony with the
well-known relationship of the three classes of organic foodstuffs to
oxygen. In other words, fats would undergo combustion most readily,
carbohydrates next, and lastly the nitrogenous or albuminous compounds.
In reality, however, proteid matter is decomposed in largest quantity;
a generous addition of proteid food is always accompanied by an
increased consumption of oxygen. Yet oxygen is not the inciting cause
of the proteid decomposition, as is seen from the fact that in muscle
work, where the intake of oxygen is greatly increased, there is no
noticeable change in the amount of proteid material broken down.
Plainly, in the body we have to deal not with a direct oxidation of
the complex compounds of the tissues or of the food, but rather with
a gradual cleavage of these higher compounds into simpler substances,
these latter undergoing progressively a still further breaking down
with intake of oxygen. To repeat, oxygen is not the _cause_ of the
decompositions within the body, but the extent of the breaking down of
the tissue or food material is the determining factor in the amount
of oxygen taken on and used up. The products of decomposition contain
more oxygen than the original substances undergoing the breaking down
process, which means that oxygen is taken from the blood and used in
the physiological combustion that is going on. It is not, however,
strictly a combustion process; it is more complicated and more gradual
than ordinary combustion, involving first of all a series of what may
be termed oxidative cleavages, in which large molecules are gradually,
step by step, broken down into simpler molecules, and these latter then
oxidized to still simpler forms. Hence, we find the oxidative changes
preceded by a variety of alterations in which oxygen may take no part
whatever; such as hydrolytic cleavage, where the elements of water are
taken on as a necessary step in the cleavage process; dissociation of
a simple sort, as when a large molecule breaks up directly into smaller
molecules, etc.
These statements by no means detract from the importance of oxygen in
the katabolic processes of the body, but it is physiological oxidation
that we have to do with, and not simple combustion. Oxygen is not the
direct cause of the transformations taking place in the body. As one
looks over the history of progress in our knowledge of nutrition from
the time of Lavoisier to the present, it is easy to note the gradual
change of view regarding oxidation in the living organism. Step by
step, it has been demonstrated that there are many factors involved in
this breaking down of complex substances; that while oxygen is an ever
present requirement, there are other equally important factors to be
taken into account. The contrast between the older views and those now
current is clearly shown by the difference in attitude regarding the
_place_ in the body where oxidation occurs. Thus, in the earlier days,
when the view was gradually gaining ground that nutritional changes
were mainly the result of oxidation, and that the oxygen drawn into the
lungs in inspiration was a primary factor, then, as we have seen, the
lungs were considered as the laboratory where the transformation takes
place. This view, however, was soon exploded, and next we find the
blood, the lymph, and other fluids, but especially the blood, looked on
as the locality where oxidation occurs. This was indeed quite a natural
view to hold, since the blood is the carrier of oxygen, but we now
know, in harmony with the fact that the breaking down of complex food
material is a complicated process, involving various kinds of chemical
change, that these katabolic processes are not located in any one
place, but occur all over the body wherever there are active tissues.
As has been previously stated, the human body is a “nation” of cells,
all of which are more or less active, and it is in these miniature
laboratories mainly that oxidation and all the other nutritional
changes coincident to life take place. Muscle tissue and nerve tissue,
the large secreting glands, such as the liver, stomach, and pancreas,
all are the seat of oxidative and other changes which we class under
the broad term of nutritional. To these cells, therefore, we must
look for an explanation of the causes of oxidation, and the other
transformations of a kindred nature that take place in the body.
In our brief survey of digestion, and of the methods there followed
for the proper utilization of the organic foodstuffs, it was seen
that the unorganized ferments or enzymes are the active agents in
accomplishing the breaking down of proteids, and the less profound
alteration of fats and carbohydrates. Is it not possible that the
tissues of the body are likewise supplied with enzymes of various
types, and that upon these powerful agents rests the responsibility
for the different kinds of decomposition, oxidation and other changes,
that take place in the body? Some years ago much interest was aroused
by the observation that certain glands in the body, if simply warmed
at body temperature with water, in the presence of some germicidal
agent sufficient to prevent putrefactive changes, underwent what is
now termed autodigestion, _i. e._, a process of self-digestion, with
formation of various products, notably such as would naturally result
from the breaking down of proteid material by ordinary proteolytic
enzymes. This would seem to imply the presence in the glands of
a proteid-splitting enzyme, the products formed being proteoses,
peptones, amino-acids, etc., just such products as result from the
action of trypsin. To-day, we know that practically all tissues and
organs can, under suitable conditions, undergo autolysis, and in many
instances the enzymes themselves can be separated from the tissues by
appropriate treatment. Liver, muscle, lymph glands, spleen, kidneys,
lungs, thymus, etc., all contain what are very appropriately called
intracellular enzymes. These enzymes are of various kinds. Especially
conspicuous are the hydrolytic, proteid-splitting enzymes, which
behave in a manner quite similar to, if not identical with, that of
the digestive enzymes of the gastro-intestinal tract, _i. e._, pepsin,
trypsin, and erepsin. Further, there are other hydrolytic cleavages
taking place in tissue cells, such as the cleavage of fats, due as we
now know to intracellular enzymes of the lipase type, and by which
neutral fats are split apart into glycerin and fatty acid. Again, there
are in many organs intracellular enzymes which act upon the complex
nucleoproteids of the tissue, causing them to break apart into proteid
and nucleic acid, the latter being further broken down by other enzymes
with liberation of the contained nuclein or purin bases. Many other
chemical reactions are brought about by specific enzymes of various
kinds, present in the cells of particular glandular organs. Thus,
intracellular enzymes have been found, as in the liver, which are able
to transform amino-acids into amides, and still others capable of
splitting up amides.
Equally important, and even more suggestive, are the data which have
been collected recently regarding oxidative processes in the tissues
of the body. Specific ferments, known as oxidases, are found widely
distributed in many organs and tissues, and it is difficult to escape
the conclusion that as intracellular enzymes they have an important
part to play in some, at least, of the transformations characteristic
of tissue katabolism.[20] As a single example, mention may be made of
aldehydase, which accomplishes the oxidation of substances having the
structure of aldehydes into corresponding acids. Ferments or enzymes
of this class are found in the liver, spleen, salivary glands, lungs,
brain, kidneys, etc., and they may well be considered as important
agents in the chemical transformations going on in the tissues of
the body. It would take us too far afield to enter into a detailed
consideration of these intracellular enzymes; it must suffice to
emphasize the general fact that in all the tissues and organs of the
body there are present a large number of enzymes of different types,
endowed with different lines of activity, and consequently capable
of accomplishing a great variety of results in metabolism. Oxidation
may still be a dominant feature in nutrition, oxidative changes may
characterize more or less every tissue and organ in the body, but the
processes are subtle and are not to be defined in harmony with simple
chemical or physical laws. The living cell, with its intracellular
enzymes, is the guiding and controlling power by which the processes of
katabolism are regulated in harmony with the needs of the body. Complex
organic matter is broken down step by step in the various tissues, with
gradual liberation of the contained energy; processes of hydrolytic
cleavage alternate with processes of oxidation, the molecules acted
upon growing smaller with each downward step, until at last the final
end-products are reached, viz., carbon dioxide, water, and urea, which
the body eliminates through various channels as true physiological
waste-products.
[20] See M. Jacoby: Ueber die Bedeutung der intracellulären Fermente
für die Physiologie und Pathologie. Ergebnisse der Physiologie,
Erster Jahrgang, 1. Abtheilung, p. 230.
It will be advisable for us to consider briefly some of these
intermediary products of tissue metabolism, since in any discussion
of nutritive changes it is quite essential to have some understanding
of the chemical relationship existing between the various products
which result from the breaking down of proteid and other materials in
tissue katabolism. This is especially true of proteid material, since
in the gradual disintegration of this substance in tissue metabolism
many intermediary bodies are formed, which undoubtedly exercise some
physiological influence prior to their transformation into simpler
bodies, with ultimate formation of the final product, urea. As has
been pointed out so many times, the proteid foods are peculiar in that
they alone contain the necessary nitrogen, and in the peculiar form
able to meet the physiological requirements of the body. Variations in
the proteid intake are of necessity accompanied by variations in the
formation of nitrogenous intermediary products, and both quality and
quantity of these substances must be given due attention in any study
of nutrition. Further, it is only by an understanding of the general
or ground structure of proteids that we can hope to attain knowledge
of the processes going on in the different tissues and organs in
connection with metabolism, while a true appreciation of the chemical
peculiarities of the individual proteids will help to explain the
different nutritional value of vegetable as contrasted with animal
proteids.
Our understanding of the chemical structure of any organic substance
is based primarily upon a study of the decomposition products which
result from its breaking down, under the influence of various chemical
agencies. Simple proteid substances when acted upon by pancreatic
juice reinforced by the enzyme erepsin, or when boiled with dilute
acids, undergo hydrolytic cleavage with ultimate formation of a large
number of relatively simple bodies, mostly amino-acids, the chemical
structure of which throws some light upon the nature of the proteid.
Thus, in the pancreatic digestion of proteid in the intestine we may
adopt the following scheme as showing in a general way the progressive
transformation that occurs, understanding at the same time that like
transformations may be accomplished by corresponding intracellular
enzymes in the tissues and organs of the body; and further, that by the
long-continued action of hydrolytic agents there is a complete breaking
down into amino-acids and other simple products.
Native Proteid
/\
/ \
/ \
Protoproteose Heteroproteose : Primary proteoses
| |
Deuteroproteose Deuteroproteose : Secondary proteoses
| |
Peptone Peptone
| |
Amino-acids Amino-acids
Among these end-products, or amino-acids, are leucin, tyrosin, aspartic
acid, glutaminic acid, glycocoll, arginin, lysin, histidin, and
likewise the peculiar aromatic body tryptophan. The chemical make-up
of these substances may be indicated by the following structural
formulæ, which, if even only partially understood, will suggest to the
non-chemical mind some idea of close chemical relationship:
CH(NH_{2})COOH
/ CH(NH_{2})COOH
CH_{2} |
\ CH_{2}-COOH
CH_{2}-COOH
Glutaminic acid Aspartic acid
CH_{3}
CH_{2}-NH_{2} \
| CH-CH_{2}-CH(NH_{2})-COOH
COOH /
CH_{3}
Glycocoll Leucin
OH
/
C_{6}H_{4}
\
CH_{2}-CH(NH_{2})COOH
Tyrosin
C·CH_{2}·CH·(NH_{2})·COOH
/ \\
C_{6}H_{4} CH
\ /
NH
Tryptophan
CH_{2}-NH CH_{2}-NH_{2} CH--N
| \ | || \\
CH_{2} C--NH_{2} CH_{2} || CHµ
| // | || /
CH_{2} NH CH_{2} C--NH
| | |
CH·NH_{2} CH_{2} CH_{2}
| | |
COOH CH-NH_{2} CH-NH_{2}
| |
COOH COOH
Arginin Lysin Histidin
In these various decomposition products there is apparent certain
definite lines of resemblance, on which is based one or more
suggestions regarding possible ways in which these chemical groups are
linked, or bound together, in the proteid molecule. Thus, there is
apparently present a complex or nucleus which may be indicated as
| |
HC-NH-CO- also HC-NH-C(NH)-
| |
The proteid molecule is presumably built up of amino-acids variously
joined together, this synthesis being accomplished, doubtless, by the
condensation of different types of amino-acids, in which the first
of the above groups represents the more common method of union. We
may indeed conjecture that such methods of condensation take place in
the human body, in the epithelial cells of the intestine, and in the
tissues in general; and that by such methods, construction of proteid
is accomplished out of the various fragments split off by digestion,
etc. In a tentative way, the principle may be illustrated by the fusion
of leucin and glutaminic acid,--following Hofmeister’s suggestion,--in
which a still larger complex is formed:
: :
--CO-:-NH--CH--CO--NH--CH--CO-:-NH--
: | | :
C_{4}H_{9} (CH_{2})_{2}
|
CO·OH
Leucin Glutaminic acid
In this way, step by step, the proteid molecule is built up, and
naturally in katabolism the proteid breaks down along certain definite
lines of cleavage, with formation of katabolic products containing
those groups, or chemical nuclei, which characterize the different
proteid molecules. For it is to be clearly understood that there are
many different forms of proteid, perhaps superficially alike, but
possessed of physiological individuality. This is well illustrated
by the two primary proteoses formed in digestion. As will be
recalled, there are at first two proteoses produced, protoproteose
and heteroproteose. These are, superficially at least, not radically
unlike; they possess essentially the same percentage composition, but
when broken down by vigorous chemical methods they show a totally
different make-up. In other words, at the very beginning of digestion
there is a splitting up of the proteid into two parts, which have
quite a different chemical structure, as is clearly indicated by the
difference in the character and amount of the decomposition products
yielded by hydrolytic cleavage. Thus, heteroalbumose as derived from
blood-fibrin contains 39 per cent of its total nitrogen in basic form,
_i. e._, in a form which goes over into the basic bodies, arginin,
lysin, and histidin, etc. On the other hand, protoalbumose from the
same source yields hardly 25 per cent of basic nitrogen. Further,
heteroalbumose yields only a very small amount of tyrosin, while
protoalbumose gives on decomposition a large amount of this substance.
Again, heteroalbumose furnishes a large yield of leucin and glycocoll,
while protoalbumose gives no glycocoll and only a little leucin.
Obviously, these two proteoses have an inner structure quite divergent
one from the other, and owing to this fact they must play a quite
different rôle in metabolism.
Even greater differences in inner chemical structure are found among
native proteids. By way of illustration, we may take egg-albumin,
the casein of cow’s milk, gliadin of wheat, and the edestin of hemp
seed. These are all typical proteids; they are all useful as food, but
they are radically different in their inner chemical structure, as is
clearly indicated by the following data,[21] which show the percentage
yield of the different amino-acids and ammonia:
[21] These data were furnished the writer by Dr. Thomas B. Osborne,
and represent in large measure the results of his own chemical work.
+--------+-------+--------+----------+--------+------+---------+--------+
| | | |Glutaminic| | | | |
| |Leucin.|Tyrosin.| Acid. |Arginin.|Lysin.|Histidin.|Ammonia.|
+--------+-------+--------+----------+--------+------+---------+--------+
|Egg- | | | | | | | |
| albumin| 6.1 | 1.1 | 9.0 | ... | ... | ... | 1.6 |
|Casein | 10.5 | 4.5 | 10.7 | 4.8 | 5.8 | 2.6 | 1.9 |
|Gliadin | 5.7 | 1.2 | 37.3 | 3.2 | 0 | 0.6 | 5.1 |
|Edestin | 19.9 | 2.7 | 14.0 | 14.2 | 1.6 | 2.2 | 2.3 |
+--------+-------+--------+----------+--------+------+---------+--------+
These are not mere technical differences, but they represent
divergences of structure which cannot help counting as material factors
in nutritional processes. Especially noticeable is the large yield of
glutaminic acid from wheat proteid, as contrasted with the proteid
(casein) of animal origin. As a rule, glutaminic acid forms a larger
proportion of the decomposition products of vegetable than of animal
proteids. Similarly, arginin is present in much larger proportion
in most vegetable proteids than in most animal proteids. While many
other data more or less trustworthy might be added, these figures
will suffice to emphasize the main point under discussion, viz., that
individual proteids show marked variation in the amount of the several
amino-acids which serve as corner-stones or nuclei in the building
up of the molecule, and consequently they must yield correspondingly
different katabolic products when serving the body as food.
Turning now to another phase of tissue metabolism, we may consider
briefly the nucleoproteids and their characteristic decomposition
products; bodies which are widely distributed as cleavage products
formed in the disintegration of most cell protoplasm, and having
special interest in nutrition because of their chemical relationship
to that well-known substance, uric acid. Nucleoproteids of some type
are found in all cells; consequently they are present in all tissues,
in all glandular organs, and their widespread distribution constitutes
evidence of their great physiological importance. Nucleoproteids are
compound substances made up of some form of proteid and nucleic acid.
By simple hydrolysis with dilute mineral acids they are broken down
into proteid, phosphoric acid, and one or more bodies known as nuclein
bases. Of these latter substances, there are four well-defined bodies,
viz., adenin, hypoxanthin, guanin, and xanthin, which from their
peculiar chemical constitution are known as “purin bases.” In the
body, there is present in many cells a peculiar intracellular enzyme
termed _nuclease_, which has the power of liberating these purin bases
from their combination as a component part of tissue nucleoproteids,
or of the contained nucleic acid. In autolysis or self-digestion of
many glands, such as the spleen, thymus, etc., this chemical reaction
is easily induced by action of the contained nuclease. Further, the
liberated purin bases then undergo change because of the presence of
certain deamidizing enzymes, and as a result guanin is transformed into
xanthin, and adenin is converted into hypoxanthin. These ferments are
true intracellular enzymes, and are termed respectively _guanase_ and
_adenase_. The real essence of the reaction they accomplish is clearly
indicated by the following formulæ, which likewise show the chemical
nature and relationship of the four substances:
HN--CO HN--CO
| | | |
H_{2}N·C C--NH + H_{2}O = CO C--NH + NH_{3}
|| || \ || || \
|| || CH || || CH
|| || // || || //
N--C--N HN--C--N
Guanin Xanthin
N==C·NH_{2} HN--CO
| | | |
HC C--NH + H_{2}O = HC C--NH + NH_{3}
|| || \ || || \
|| || CH || || CH
|| || // || || //
N--C--N N--C--N
Adenin Hypoxanthin
These two enzymes are typical hydrolyzing enzymes, but it is to be
noted that there is not only a taking on of water with a retention of
the oxygen, but there is also a giving off of ammonia, by which the
transformation is made possible. Adenin is known as an amino-purin
and guanin as an amino-oxypurin, while hypoxanthin is an oxypurin and
xanthin a dioxypurin. In other words, the two intracellular enzymes
are able to transform the two amino-purins into the corresponding
oxypurins; _i. e._, the enzymes are deamidizing ferments, liberating
the NH_{2} group of the adenin and guanin and thus forming two new
compounds. These reactions, though more or less technical, are
emphasized in this way not merely because they illustrate the action
of intracellular enzymes in intermediary metabolism, thus affording a
striking example of the gradual changes that take place in ordinary
katabolic processes, but especially because they throw light upon the
production of another substance common in body metabolism, viz., uric
acid. It has long been known that nucleoproteids, nucleins, and other
compounds containing these purin radicles, when taken as food, cause
at once an increased output of uric acid, and it has been clearly
recognized that in some way this latter substance, as a product of
metabolism, must come from the transformation of nuclein bases. To-day,
we understand that in many tissues, as in the liver, spleen, lungs,
and muscle, there is present a peculiar oxidizing ferment, an oxidase,
by the action of which hypoxanthin can be converted into xanthin, and
the latter directly oxidized to uric acid. This conversion into uric
acid is purely a process of oxidation, brought about by a typical
intracellular oxidase, known specifically as “xanthin oxidase,” the
reaction involved being as follows:
HN--CO HN--CO
| | | |
CO C--NH + O = CO C--NH
| || \ | || \
| || CH | || CO
| || // | || /
HN--C--N HN--C--NH
Xanthin Uric acid
From these several reactions, it is clear how various intracellular
enzymes working one after the other are able gradually to evolve uric
acid from tissue nucleoproteids. Further, it is to be noted that there
is another tissue oxidase--contained principally in the kidneys,
muscle, and liver--which has the power of oxidizing and thus destroying
uric acid, with formation, among other substances, of urea. Remembering
that urea has the following chemical constitution
NH_{2}
/
C==O
\
NH_{2}
it is easy to see, by comparison of the formulæ, how uric acid might
easily yield two molecules of urea through simple oxidation. In this
way, excess of uric acid produced in the body can be converted into
urea, and in this harmless form be excreted from the system.
Finally, reference should be made here to several other products of
tissue metabolism, products of the breaking down of proteid matter in
the body, since they are liable to prove of interest to us in other
connections. Thus creatin, abundant in the muscle and other places; the
related substance creatinin, present in the urine; methyl guanidin,
a decomposition product of creatin; and urea, all call for a word of
description. The chemical relationship of these bodies is clearly
indicated by the following formulæ:
NH_{2} NH-------
/ / \
C==NH C==NH CO
\ \ /
N(CH_{3})CH_{2}COOH N(CH_{3})CH_{2}
Creatin Creatinin
NH_{2} NH_{2}
/ /
C==NH C==O
\ \
NH(CH_{3}) NH_{2}
Methyl guanidin Urea
Creatinin is chemically the anhydride of creatin, _i. e._, it can be
formed from creatin by the simple extraction of one molecule of water,
H_{2}O. Creatin, by hydrolytic cleavage, will break down into one
molecule of urea and one molecule of sarcosin or methyl glycocoll, as
shown in the following equation:
NH_{2} NH_{2}
/ CH_{2}·NH·(CH_{3}) /
C==NH + H_{2}O = | + C==O
\ COOH \
N (CH_{3}) CH_{2}COOH NH_{2}
Creatin Sarcosin Urea
Methyl guanidin is a decomposition product of creatin, while guanidin,
as can be seen from the formula, is like urea, excepting that the
group NH replaces the oxygen of urea. These simple statements will
suffice for our present purpose, viz., to indicate the more or less
close chemical relationships existing between many of these nitrogenous
decomposition products resulting from proteid katabolism; also to
suggest how by slight chemical alteration one decomposition product
may be resolved into another related substance in the processes of
katabolism. Our conception of the processes involved in proteid
katabolism is that of a series of progressive chemical decompositions,
in which intracellular enzymes play the all-important part. The
intermediary products formed are definite bodies because of the
specific nature of the active enzymes, and, secondly, because of the
chemical nature of the substances acted upon. In other words, oxidation
in the animal body takes the shape of a series of well-defined chemical
reactions, in which chemical constitution and specific enzyme action
are the predetermining cause. In the absence of the particular chemical
groups, the oxidase is unable to bring about oxidation, or, given the
proper compound or mother substance in the absence of the specific
oxidase, there is no oxidation. Hence, oxidation in the animal body
is not the result of simple combustion, but, on the contrary, it
consists of a series of orderly chemical processes, each one of which
is presided over by an intracellular enzyme, specific in its nature,
in that it is capable of acting only upon substances having a certain
definite constitution, and leading invariably to a certain definite
result. The processes which years ago were considered as due to the
peculiar vital properties of the tissue cells, and which were supposed
to be entirely dependent upon their morphological and functional
integrity, are now seen to be due primarily to a great variety of
enzymes, manufactured indeed by the living cells, but capable of
manifesting their activity even when free from the influence of the
living protoplasm. The varied processes of tissue katabolism are the
result of orderly and progressive chemical changes, in which cleavage,
hydrolysis, reduction, oxidation, deamidization, etc., alternate with
each other under the influence of specific enzymes, where chemical
constitution and the structural make-up of the various molecules are
determining factors in the changes produced.