SOURCE OF THE ENERGY OF MUSCLE WORK, WITH SOME THEORIES OF PROTEID
METABOLISM
TOPICS: Relation of muscle work to energy exchange. Views of Liebig.
Experimental evidence. Relation of nitrogen excretion to muscle
work. Significance of the respiratory quotient in determining
nature of the material oxidized. Fats and carbohydrates as source
of energy by muscles. Utilization of proteid as a source of energy.
Formation of carbohydrate from proteid. Significance of proteid
metabolism. Theories of Carl Voit. Morphotic proteid. Circulating
proteid. General conception of proteid metabolism on the basis of
Voit’s theories. Pflüger’s views of proteid metabolism. Rapidity of
elimination of food nitrogen. Methods by which nitrogen is split off
from proteid. Theories of Folin. Significance of creatinin and of the
percentage distribution of excreted nitrogen. Endogenous or tissue
metabolism. Exogenous or intermediate metabolism. Needs of the body
for proteid food possibly satisfied by quantity sufficient to meet
the demands of tissue or endogenous metabolism. Bearings of Folin’s
views on current theories and general facts of proteid metabolism.
Large proteid reserve and voluminous exogenous metabolism probably
not needed. Importance of feeding experiments in determining the true
value of different views.
As we have already seen, every form of muscular activity begets an
increase in the energy exchange of the body. Between the two extremes
of absolute rest and excessive muscular exertion, we find differences
of 2000 calories or more per day as representing the degree of chemical
decomposition corresponding to the particular state of muscular
activity. The work of the involuntary muscles, such as have to do with
peristalsis, respiration, rhythmical beat of the heart, etc., is a
relatively constant factor, though naturally subject to some variation,
as has been pointed out in other connections. External muscular
activity, however, is the one factor above all others that modifies the
rate of energy exchange. A little longer walk, a heavier load to carry,
a steeper hill to climb, any increase great or small in the activity
of the muscles of the body, means a corresponding increase in chemical
decomposition, with increased output of the ordinary products of tissue
oxidation. The material so consumed, or oxidized, must be made good
to hold the body in equilibrium; the supplies drawn upon are to be
replaced, if the tissues of the body are to be kept in a proper state
of efficiency.
What is the nature of the material used up in connection with muscle
work? As can readily be seen, this is an important question, for on its
answer depends, in some measure at least, the character of the proper
intake, or food, to be supplied in order to make good the loss. If the
energy of mechanical work, the energy of muscle contraction, comes from
the breaking down of proteid matter alone, then obviously excessive
muscular work would need to be accompanied, or followed, by a generous
supply of proteid food. If, on the other hand, external work means
liberation of energy solely from non-nitrogenous materials, then it
is equally clear that fats and carbohydrates are the proper foods to
offset the drain incidental to vigorous muscular action.
The views of Liebig, briefly referred to in a previous chapter, held
sway over physiologists for many years. His dictum that proteid foods
were true plastic foods, entering into the structure of the tissues
of the body, and that they alone were the real sources of muscular
energy, met for a time with no opposition. It was not until the advent
of a more critical spirit, accompanied by a fuller appreciation of
the necessity of experimental evidence, that physiologists began to
test with scientific accuracy the validity of the current views. It
is worthy of note that long prior to this time, even before oxygen
was discovered, the far-sighted and resourceful John Mayow, in his
work with the various “spirits” of the body and their relation to
respiration, etc., evolved the view that muscular power has its origin
in the combustion of fat brought to the muscles by the blood and burned
there by aid of a gas or “spirit” taken from the air by the lungs, and
likewise carried to the muscles by the circulating blood. Considering
the time when Mayow lived and the dearth of true scientific knowledge
as we measure it to-day, his hypothesis was a wonderful forestalling of
present views.
It is quite obvious that the views of Liebig, if true, admit of easy
proof; since, if the energy of muscular power comes from the breaking
down of proteid, there should be a certain parallelism between the
output of nitrogen from the body and the amount of muscular work
accomplished, everything else being equal. As stated in a previous
chapter, such study of this question as was made soon disclosed the
fact that the one element above all others that seemed to influence the
output of nitrogen was the intake of proteid food. Thus, the English
investigators, Lawes and Gilbert, found by experimenting with animals
that when the latter were kept under uniform conditions of muscular
work, the amount of nitrogen excreted ran parallel with the intake
of nitrogen. Further, in the early experiments of Voit, the results
obtained clearly showed that variations in the amount of work performed
were practically without influence on the excretion of nitrogenous
waste products.
The experiment, however, that came as a death blow to the theories of
Liebig was that of Fick and Wislicenus,[43] who in 1865 made an ascent
of the Faulhorn, 6500 feet high, using a diet wholly non-nitrogenous.
From the nitrogen excreted they were able, of course, to calculate the
amount of proteid oxidized in the body during the period of work, and
found that the proteid consumed could not have furnished, at the most,
more than one-half the energy required to lift the weights of their
bodies to the top of the high peak. Further, they observed that neither
during the work period, nor immediately after, was there any noticeable
increase in the excretion of nitrogen. Obviously, as they state, the
oxidation of proteid matter in the body cannot be the exclusive source
of the energy of muscular contraction, since the measurable amount
of external work performed in the ascent of the mountain was far
greater than the equivalent of the energy capable of being furnished
by the proteid actually burned. To which may be added the fact that
considerable energy, not measurable in their experiment, must have
been employed in the work of the involuntary muscles of the body; thus
increasing by so much the difference between the muscular work actually
accomplished and the available energy from proteid consumed. It is true
that minor criticisms regarding certain details of the experiment can
be offered to-day, such as the fact that the men were, in a measure,
in a state of “nitrogen starvation,” etc., but these criticisms do
not in any degree militate against the main thesis that the energy of
muscular contraction does not come exclusively from the consumption or
breaking down of proteid, either of food or tissue. Vigorous and even
severe muscular work does not necessarily increase the decomposition
of proteid material. Dogs made to run in large treadmills, with the
same diet as on resting days, were found to excrete practically no
more nitrogen than during the days of rest. Occasionally, however,
in some one experiment the output of nitrogen would show an increase
over the output on resting days. Further, experiments made with horses
led to essentially the same result, except that greater increase in
the excretion of nitrogen was observed than with dogs. This increase
in nitrogen output, however, as a concomitant of increased muscular
activity, could be prevented by adding to the amount of carbohydrate
food.
[43] See Gesammelte Schriften von Adolf Fick. Ueber die Entstehung
der Muskelkraft. Band 2, p. 85. Würzburg, 1903.
While experiments of this nature, on man and animals, all tended to
show little or no increase in the excretion of nitrogen, as a result
of muscle work; and likewise no increase in the output of sulphur and
phosphorus, thus strengthening the view that muscular energy is not the
result of proteid disintegration, there was observed marked increase
in the consumption of oxygen, and in the excretion of carbon dioxide.
Non-nitrogenous matter was thus at once suggested as the material
with which muscle chiefly does its work. There is to-day no question
of the general truth of this statement, yet there are other aspects
of the problem to be considered before we can lay it aside. Pflüger,
working with dogs, and Argutinsky, experimenting on himself by arduous
mountain climbing, reached conclusions seemingly quite opposed to what
has just been said. Their results, however, admit of quite a different
interpretation from what they were disposed to attach to them. Thus,
Pflüger[44] would go back to the old view that all muscle work is at
the expense of proteid material, because lean dogs fed mainly, or
entirely, on meat and made to do an excessive amount of work were found
by him to excrete nitrogen somewhat in proportion to the amount of work
done. Argutinsky,[45] likewise, in his mountain climbing carried to the
point of fatigue, and with a high proteid intake likewise, saw in the
increased output of nitrogen a suggestion of the same idea. In reality,
however, their results merely prove that, under some circumstances,
proteid may serve as the chief source of muscular energy; as when the
body is poor in fat and carbohydrate, or when the intake consists
solely of proteid matter. In other words, muscular work may result in
an increased excretion of nitrogen when the work is very severe, and
there is not a corresponding increase in the fats or carbohydrates
(fuel ingredients) of the food. In the words of Bunge,[46] “we might
assume _à priori_, on teleological grounds, that in the performance
of its most important functions the organism is to a certain extent
independent of the quality of its food. As long as non-nitrogenous
food is supplied in adequate quantity or is stored up in the tissues,
muscular work is chiefly maintained from this store. When it is gone
the proteids are attacked.”
[44] Pflüger: Die Quelle der Muskelkraft. Pflüger’s Archiv für die
gesammte Physiologie, Band 50, p. 98.
[45] Argutinsky: Muskelarbeit und Stickstoffumsatz. Ibid., Band 46,
p. 552.
[46] Bunge: Textbook of Physiological and Pathological Chemistry.
Second English Edition, 1902, p. 352.
There is no question that the energy of muscular contraction can come
from all three classes of organic foodstuffs. Voluntary muscular
movement is under the control of the nervous system, and when the
stimulus is applied the muscle is bound to contract, provided of
course there is sufficient energy-containing material present to
furnish the means. Muscle tissue, like other tissues and organs, has
a certain power of adaptability, by which it is able to do its work,
even though it is not adequately supplied with its preferred nutrient.
While proteid is plainly not the material from which the energy of
muscular contraction is ordinarily derived, it is equally evident
that in emergency, as when the usual store of carbohydrate and fat is
wanting, proteid can be drawn upon, and in such cases vigorous work
may be attended with increased nitrogen output. In harmony with this
statement, we find on record in recent years many experiments, both
with man and animals, where severe muscular labor is accompanied by an
excretion of nitrogen beyond what occurs on days of rest; but by simply
adding to the intake of non-nitrogenous food this increased outgo of
nitrogen is at once checked. With moderate work, the nitrogen outgo
is rarely influenced; it is only when the work becomes excessive, or
the store of non-nitrogenous reserve is small and the intake of the
latter food is limited, that proteid matter is drawn upon to supply the
required energy.
Recalling what has been said regarding the significance of the
respiratory quotient, it is obvious that we have here a means of
acquiring information as to the character of the material that is
burned up in the body during muscular work. Increased metabolism
of carbohydrate will necessarily result in raising the respiratory
quotient, and if the latter food material alone is involved the
respiratory quotient must naturally approach 1.0. Zuntz, however, has
clearly shown that vigorous muscular activity does not materially
change the respiratory quotient; except in cases of very severe work,
where the oxygen-supply of the muscles is interfered with. Indeed, the
muscles may be made to do work sufficient to increase the consumption
of oxygen threefold or more, without any change in the respiratory
quotient being observed. And as there is frequently no change whatever
in the output of nitrogen under these conditions, it follows that the
energy of the muscle work must have come from the decomposition of
non-nitrogenous material. If carbohydrates alone were involved, the
respiratory quotient would obviously undergo change. Since, however,
this remains practically stationary, we are led to the conclusion that
fat must be involved in large degree, in addition to carbohydrate.
In this connection, it is a significant fact that with _fasting_
animals, where the store of carbohydrate material is more or less used
up, severe muscle work may be accomplished without any appreciable
increase in nitrogen output, thus showing that proteid material is not
involved and clearly pointing to fat as the source of the muscular
energy. Thus, in an experiment referred to by Leathes, a dog on the
sixth and seventh day of starvation was made to do work in a treadmill
equivalent to climbing to a height of 1400 meters, yet the output
of nitrogen was increased from six to only six and a half grams.
Obviously, not much of the energy of this muscle work could have come
from the breaking down of proteid, but it must have been derived mainly
from the oxidation of fat. There is abundant evidence that fat can be
used as a source of energy by muscles, as well as carbohydrates and
proteids, and there is every reason for believing that the yield of
work for a given amount of chemical energy in the form of fat is as
good as in the case of either of the other two substances. In fact, the
observations of Zuntz show that fat can be used just as economically
by the body for muscle work as either carbohydrates or proteid. Thus,
in one experiment,[47] he determined the oxygen-consumption and
respiratory quotient in a man resting and working on three different
diets--one principally fat, one principally carbohydrate, and the other
principally proteid--and found that slightly less oxygen and energy
were required to do work on the fat diet than on the others. This is
clearly shown in the following table:
[47] Quoted from Leathes: Problems in Animal Metabolism, p. 100.
+------------+------------------+------------------+------+----------------+
| | | | | Per |
| | Resting. | Working. |Kilo- | Kilogram-meter |
| | | |gram- | of Work. |
| Diet +--------+---------+--------+---------+meters+------+---------+
|Principally.| Oxygen |Respira- | Oxygen |Respira- | of |Oxygen|Calories.|
| |Used per| tory |Used per| tory | Work | Used.| |
| | Minute.|Quotient.| Minute.|Quotient.| Done.| | |
+------------+--------+---------+--------+---------+------+------+---------+
| | c.c. | | c.c. | | | c.c. | |
|Fat | 319 | 0.72 | 1029 | 0.72 | 354 | 2.01 | 9.39 |
|Carbohydrate| 277 | 0.90 | 1029 | 0.90 | 346 | 2.17 | 10.41 |
|Proteid | 306 | 0.80 | 1127 | 0.80 | 345 | 2.38 | 11.35 |
+------------+--------+---------+--------+---------+------+------+---------+
From these data, we see that per kilogram-meter of work less energy
was required and less oxygen consumed with fat than with either of the
other two foodstuffs; but practically, fat and carbohydrate as sources
of muscle energy have about the same value.
Much stress is ordinarily laid upon the importance of a large intake
of proteid food whenever the body is called upon to perform severe, or
long-continued, muscular work; but in view of what has been stated it
may be questioned whether there is any real physiological justification
for such custom. The pedestrian Weston,[48] who in 1884 walked 50 miles
a day for 100 consecutive days, was found by Blyth during a period of
five days to consume in his food 37.2 grams of nitrogen a day, while he
excreted only 35.3 grams, leaving a balance of 1.9 grams of nitrogen
per day apparently stored in the body. His daily food during this
period was composed of 262 grams of proteid, 64.6 grams of fat, and 799
grams of carbohydrate, with an estimated fuel value of 4850 calories.
Yet he performed this large amount of work daily, and still laid by a
certain amount of proteid on a ration, the energy value of which would
not ordinarily be considered high for the muscular work to be done.
Fourteen years prior to this, Weston, while in New York, was carefully
studied by Dr. Flint during a period of 15 days, on 5 of which he
walked a total of 317 miles. His diet was essentially a proteid diet,
consisting principally of beef extract, oatmeal gruel, and raw eggs.
Nitrogen intake and output were carefully compared during the days of
rest and during the days of work, with the results tabulated.
[48] This and the following account of Weston are taken from Bulletin
No. 98, U. S. Department of Agriculture, Office of Experiment
Stations. The effect of severe and prolonged muscular work on food
consumption, digestion, and metabolism. By W. O. Atwater and H. C.
Sherman, p. 13.
+--------------+----------------+--------+--------------------------+
| | | | Nitrogen. |
| | | +-----+------+------+------+
| | |Duration| In | In | In |Gain +|
| Period. | Occupation. |of Test.|Food.|Urine.|Excre-| or |
| | | | | |ment. |Loss -|
+--------------+----------------+--------+-----+------+------+------+
| | | days |grams|grams |grams |grams |
|Fore period |Comparative rest| 5 | 22.0| 18.7 | 1.4 | +1.9 |
| | | | | | | |
|Working period|Walking 62 miles|{ | | | | |
| | per day |{ 5 | 13.2| 21.6 | 1.6 |-10.0 |
| | | | | | | |
|After period |Rest | 5 | 28.6| 22.0 | 2.2 | +4.4 |
+--------------+----------------+--------+-----+------+------+------+
In this case it will be noted that the daily ration was comparatively
small, and, further, that during the working period the subject
consumed much less proteid than on the resting days. Moreover, when
we remember that the total energy value of his diet must have been
quite small, it is not at all strange that in the laborious task of
walking 62 miles a day he should have temporarily drawn upon his store
of body proteid to the extent of 62.5 grams, or 10 grams of nitrogen a
day. Such experiences, however, do not by any means constitute proof
that in excessive muscular work there is need for the consumption of
correspondingly increased quantities of proteid food, or that the
energy of muscular work comes preferably from the breaking down of
proteid material. Carbohydrate and fat unquestionably take precedence
over proteid in this respect, and we may accept as settled the view
that in all practical ways carbohydrate and fat stand on an equal
footing as sources of muscular energy. Less clear, perhaps, is the
question as to how these two radically different types of organic
material are utilized by the muscle. It has been a favorite belief
among some physiologists that the contracting muscle makes use of
only one substance as the direct source of its energy, and that this
substance is the sugar dextrose. This view would seemingly imply that
fat and proteid must undergo alteration prior to their utilization
by the muscle; that, possibly, the carbon of the fat and proteid
is transformed into sugar before the muscle can make use of it. So
far as fat is concerned, this view is not supported by the facts
available, since experiments show that the heat and energy liberated
in the utilization of a given amount of fat in muscle work are in
harmony with the energy value of the fat; in other words, the fat is
apparently burned, or oxidized, directly, without undergoing previous
transformation into any form of carbohydrate; or, if transformation
does occur, under some conditions, it must take place within the muscle
and without loss of energy. The practical significance of these facts
is at once apparent, for if fat, in order to be available as a source
of muscle energy, must first undergo conversion into sugar, it would
be far more economical from a physiological standpoint to replace the
fat of the diet with carbohydrate in any attempt to provide suitable
nourishment for the working muscle. We may safely conclude, however,
that fat and carbohydrate, as previously suggested, are in reality both
capable of direct metabolism by the muscular tissue, and that each is
of value as a source of muscular energy in proportion to its heat of
combustion, yielding substantially the same proportion of its potential
energy in the form of mechanical work.
Regarding the utilization of proteid as a source of energy by the
muscle, there are many grounds for believing that here the body
has to deal with certain alterations, before the proteid can be
made available. We may indeed conjecture the transformation of a
non-nitrogenous portion of the proteid molecule into carbohydrate, as
a necessary step in its utilization for muscle work. It is certainly
true that in the ordinary katabolic processes, through which proteid
passes, there is a tendency for the nitrogen-containing portion to
be quickly split off and eliminated, leaving a carbonaceous residue
which may represent as much as 80 per cent of the total energy of the
original proteid. This so-called carbon moiety of the proteid molecule
is apparently much less rapidly oxidized than the nitrogenous portion,
and may indeed be temporarily stored in the body, in the form of fat or
carbohydrate.[49] We have very convincing proof that the carbohydrate
glycogen can be formed from proteid. Thus, the feeding of proteid to
warm-blooded animals may be accompanied by an accumulation of glycogen
in the liver. This is interpreted as meaning that in the cleavage
of proteid by digestion the various nitrogenous products formed are
somewhere, probably in the liver, still further acted upon; the
contained nitrogen with some of the carbon being converted into urea,
while the non-nitrogenous residue is transformed into glycogen, or
sugar. That some such change takes place, or, more specifically, that
carbohydrate does result from proteid is more strikingly shown in human
beings suffering with diabetes. In severe forms of this disease, all
carbohydrate food consumed is rapidly eliminated through the kidneys in
the form of sugar, the body having lost the power of burning sugar. If
such a person is placed upon a diet composed exclusively of proteid,
sugar still continues to be excreted, and there is observed a certain
definite relationship between the nitrogen output and the excretion of
sugar, thus implying that they have a common origin.
[49] See Leo Langstein: Die Kohlehydratbildung aus Eiweiss.
Ergebnisse der Physiologie, Band 3, Erster Theil, p. 456.
See also, Lüthje: Zur Frage der Zuckerbildung aus Eiweiss. Archiv für
d. gesammte Physiologie, Band 106, p. 160.
Further, there are certain drugs, such as phloridzin, which, when
introduced into the circulation, set up a severe diabetes and
glycosuria. Dogs treated in this way, fed solely on proteid or even
starved for some time, will continue to excrete sugar, and as in the
previous instance, there is observed a certain definite ratio between
the nitrogen output and the elimination of sugar; thus leading to
the conclusion that both arise from the destruction of the proteid
molecule. Careful study of this ratio of dextrose to nitrogen has led
Lusk to the conclusion that full 58 per cent of the proteid may undergo
conversion into sugar in the body. Hence, it is easy to see how in
muscle work, when proteid is the sole source of the energy of muscular
contraction, the work accomplished may still result from the direct
oxidation of carbohydrate material, indirectly derived from the proteid
molecule. It requires no argument, however, to convince one that such a
procedure for the normal individual is less economical physiologically
than a direct utilization of carbohydrate and fat, introduced as such
and duly incorporated with the muscle substance. Consequently, in the
nourishment of the body for vigorous muscular work, there is reason
in a diet which shall provide an abundance of carbohydrate and fat;
proteid being added thereto only in amounts sufficient to meet the
ordinary requirements of the body for nitrogen and to furnish, it may
be, proper pabulum for the development of fresh muscle fibres, where,
as in training, effort is being made to strengthen the muscle tissue
and so enable it to do more work. Increase in proteid food may help to
make new tissue, but the source of the energy of muscle work is to be
found mainly in the breaking down of the non-nitrogenous materials,
carbohydrate and fat.
In view of these facts, we may advantageously consider next the real
significance of the proteid metabolism of the body. As we have seen, a
meal rich in proteid leads at once--within a few hours--to an excretion
of urea equivalent to full 50 per cent of the nitrogen of the ingested
proteid, while a few hours later finds practically all of the nitrogen
of the intake eliminated from the body. Further, it is to be remembered
that in a general way this occurs no matter what the condition of the
body may be at the time and no matter how large or small the amount of
proteid consumed. In other words, there is practically no appreciable
storing of nitrogen or proteid for future needs,--at least none that is
proportional to the increase in nitrogen intake, even though the body
be in a condition approximating to nitrogen starvation. Moreover, it
is to be recalled that the increased proteid metabolism attendant on
increased intake of proteid food is accompanied by an acceleration of
the metabolism of non-nitrogenous matter; thus resulting in a stirring
up of tissue change, with consequent oxidation and loss of a certain
proportion of accumulated fat and carbohydrate. Coincident with this
increased excretion of nitrogen, the output of carbon dioxide is
likewise increased somewhat, due as is believed mainly to increased
metabolism of the involuntary muscle fibres of the gastro-intestinal
tract, by action of which the accelerated peristalsis so characteristic
of food intake is accomplished. Further, the increased output of
carbon dioxide, under these conditions, is to be attributed also to
the greater activity of the digestive and excretory organs, naturally
stimulated to greater functional power by the presence of proteid
foods and their decomposition products. Still, as stated by Leathes,
“the two main end-products of proteid metabolism, urea and carbonic
acid, are, to a great extent, produced independently of each other,
and the reactions which result in the discharge of the nitrogen are
not those in which energy is set free, work done, and carbonic acid
produced.” In other words, there is suggested what we have already
referred to, viz., that in proteid metabolism a nitrogenous portion of
the proteid molecule is quickly split off and gotten rid of, while the
non-nitrogenous part may be reserved for future oxidation, serving as
a source of muscle energy or for other purposes. This being so, it is
plain that “proteid metabolism in so far as it is concerned with the
evolution of energy, proteid metabolism in its exothermic stages, may
be almost entirely non-nitrogenous metabolism” (Leathes).
Is there any advantage to the body, however, in this carbonaceous
residue of the proteid molecule over simple carbohydrate and fat?
Can the processes of the body be accomplished more economically,
or more advantageously, with a daily diet so constructed that the
tissues and organs must depend mainly upon this carbon moiety of
the proteid molecule for their energy-yielding material? It has been
one of the physiological dogmas of the past, that the tissues and
organs of the body, or rather their constituent cells, preferred to
use proteid for all their needs whenever it was available. If proteid
were wanting, either because of insufficient intake, or because of
excessive activity, then the tissue cells would draw upon their store
of non-nitrogenous material. Food proteid and tissue proteid, however,
were the materials preferred by the organism, so ran the argument, and
the large and incessant output of nitrogen which accompanied the intake
of proteid was accepted as proof of the general truth of this idea.
We might well question wherein lies the great advantage to the body
in this continual excretion of nitrogen; whether the loss of energy
in handling and removing the nitrogenous portion of the necessarily
large proteid intake, in order to render available the non-nitrogenous
part of the molecule, might not more than compensate for the supposed
gain? But the truly astonishing fact that the output of nitrogen runs
parallel with the intake of proteid, that the body cannot store up
nitrogen to any large extent, has been taken as conclusive evidence
that the organism prefers to use proteid for all of its requirements.
Truly, we might just as well argue that this significant rise in
the excretion of nitrogen after partaking of a proteid meal is an
indication that the body has no need of this excess of nitrogen; that
it is indeed a possible source of danger, since the system strives
vigorously to rid itself of the surplus, and that the energy-needs of
the body can be much more advantageously and economically met from fat
and carbohydrate than from the carbonaceous residue resulting from the
disruption of the proteid molecule.
In discussing these questions, we shall need to refer to several of
the current theories concerning proteid metabolism, notably, the
theories of Voit, Pflüger, and Folin. In 1867 Carl Voit,[50] of
Munich, advanced the view that the proteid material of the body exists
in two distinct forms, viz., as “morphotic” or “organized” proteid,
representing proteid which has actually become a part of the living
units of the body, _i. e._, an integral part of the living tissues;
and “circulating” proteid, or that which exists in the internal meshes
of the tissue, or in the surrounding lymph and circulating blood.
The real point of distinction here is that while one portion of the
body proteid is raised to the higher plane of living matter, _i. e._,
becomes a component part of the living protoplasm, another and perhaps
larger portion is outside of the morphological framework of the tissue,
constituting a sort of internal medium which bathes the living cells,
and acts as middleman between the blood and lymph on the one side and
the living cells on the other. According to Voit’s view, it is this
circulating proteid that undergoes metabolism; the proteid of the food
after digestion and absorption being carried to the different tissues
and organs, and then, without becoming an integral part of the living
protoplasm of the cells, it is broken down under the influence of
the latter. Obviously, small numbers of tissue cells are constantly
dying, their proteid matter passing into solution, where it likewise
undergoes metabolism. In other words, according to Voit, the great
bulk of the proteid undergoing katabolism is the circulating proteid,
derived more or less directly from the food, and which at no time has
been a part of the tissue framework; while a smaller, but more constant
amount, represents the breaking down of tissue cells. This conception
of proteid metabolism is akin to our conception of morphological and
physiological destruction. In the words of Foster: “We know that an
epithelial cell, as notably in the case of the skin, may be bodily
cast off and its place filled by a new cell; and probably a similar
disappearance of and renewal of histological units takes place in all
the tissues of the body to a variable extent. But in the adult body
these histological transformations are, in the cases of most of the
tissues, slow and infrequent. A muscle, for instance, may suffer very
considerable wasting and recover from that wasting without any loss or
renewal of its elementary fibres. And it is obvious that the metabolism
of which we are now speaking does not involve any such shifting of
histological units. On the other hand, we find these histological
units, the muscle fibre or the gland cell, for instance, living on
their internal medium, the blood, or rather on the lymph, which is
the middleman between themselves and the actual blood flowing in the
vascular channels.”
[50] See Voit: Hermann’s Handbuch der Physiologie, Band 6, p. 301.
Voit claims that the proteid dissolved in the fluids of the body
is more easily decomposable than that which exists combined in
organized form, or as more or less insoluble tissue proteid; and it
is this soluble and circulating form which, under the influence of
the living cells, undergoes destruction or metabolism. We know, as
has been previously stated, that oxidation does not take place to
any extent in the circulating blood, and similarly there is every
reason for believing that proteid metabolism does not occur in this
menstrum. Metabolism is limited mainly to the active tissues of the
body, but according to the present conception of the matter it does
not occur at the expense of the proteid of the living cells, but
involves material contained in the fluids bathing the cells; _i. e._,
it is not the organized proteid that undergoes metabolism, but the
proteid circulating in and about the internal meshes of the cells and
tissues, the living cell being the active agent in controlling the
process. Further, this view lessens the difficulty of understanding
the elimination of nitrogen after a meal rich in proteid. If it was
necessary to assume that all the proteid of our daily food is built
up into living protoplasm before katabolism occurs, it would be
exceedingly difficult to explain the sudden and rapid elimination of
nitrogen which follows the ingestion of proteid. For example, we can
hardly imagine that merely eating an excess of proteid food will lead
to an actual breaking down of the living framework of the tissues,
equivalent to the amount of nitrogen which the body at once eliminates.
Voit’s theory, on the other hand, supposes a twofold origin of the
nitrogen excreted; one part, the larger and variable portion, comes
from the direct metabolism of the circulating proteid, being the
immediate result of the ingested food and varying in amount with the
quantity of proteid food consumed; the other, smaller and less variable
in amount, has its origin in the metabolism of the true tissue proteid,
or the actual living framework of the body.
In a fasting animal, the tissues and organs of the body still contain
a large proportion of proteid matter, yet only a small fraction of
this proteid is eliminated each day, hardly 1 per cent. If, however,
proteid is absorbed from the intestine, proteid metabolism is at once
increased, and the excretion of nitrogen may be fifteen times greater
than during hunger. In other words, the extent of proteid metabolism
is not at all proportional to the total amount of proteid contained
in the body as a whole, but runs parallel in a general way with the
quantity of proteid absorbed from the intestine. Obviously, the newly
absorbed proteid is quite different in nature from the proteid which
in much larger amounts is deposited throughout the body, since it is
not organized and is so much more easily decomposable (Voit). This is
the circulating proteid of the body; it exists in solution, and it is a
significant fact that, according to Voit, the chemical transformations
that characterize proteid katabolism occur only in solution. The
organized proteid, on the other hand, is in a state of suspension,
and its katabolism, which is relatively very small, is preceded by
solution of the proteid in the fluids of the tissue, after which
its further breaking down is assumed to be the same as that of the
circulating proteid. This latter view is a fundamental part of the Voit
theory; in long-continued fasting, for example, the living protoplasm
of the various tissues and organs is of necessity drawn upon for the
nourishment of the more vital parts of the body, such as the brain,
spinal cord, etc., consequently the organized proteid is gradually
dissolved and then decomposed, after it has become liquefied and has
thus lost its organized structure.
In this conception of proteid metabolism, we picture the different
organs and tissues of the body as being permeated by a fluid which
carries variable amounts of nutritive material, the quantity of the
latter determining in a way the extent of the proteid katabolism which
shall take place. As the proteid of the food passes into the blood and
lymph, the fluids bathing the cells are correspondingly enriched, and
as a result, proteid katabolism is accelerated in parallel degree.
During hunger, on the other hand, the organized proteid of the tissue
cells is gradually liquefied and passes out into the current of the
circulating fluids. As before stated, the organized proteid as such is
never decomposed; it must first enter into solution, and then under
the influence of the living cells it undergoes disruption in the same
manner as the circulating proteid. It is thus evident that the tissue
cells and the circulating fluids permeating them bear an ever changing
relationship to each other. Excess of circulating proteid will be
attended by increased katabolism, while at the same time there may be
some accumulation of proteid in the cells, and indeed some conversion
into organized proteid. During fasting, hunger, or with an insufficient
intake of proteid food, the current will naturally be in the opposite
direction, and organized proteid will slowly, but surely, be drawn
upon.
Again, we may ask in view of these facts, of what real use to the
body is this large katabolism of circulating proteid? We can easily
understand the need of proteid to supply the loss incidental to the
breaking down of organized or true tissue proteid, but this we are led
to believe is very small in amount. Is there any real need for proteid
beyond this requirement? The physiological fuel value of proteid is
no greater than that of carbohydrate and considerably less than half
that of fat, consequently there is on the surface no apparent reason
why proteid should be used for its energy value in preference to the
non-nitrogenous foodstuffs. Further, as we have seen, the energy of
muscle work comes mainly, at least, from the breaking down of fat and
carbohydrate; proteid, in the case of the well-nourished individual,
ordinarily playing no part in this important line of energy exchange.
Lastly, in the katabolism of proteid there is the large proportion
of nitrogenous matter to be split off and disposed of before the
carbon moiety of the molecule can be rendered available. Here, we have
involved not only a loss of energy, but in addition a certain amount of
what appears to be useless labor thrown upon the liver, kidneys, and
other organs. Is there any wonder that the thoughtful physiologist,
looking at the facts and theories presented by the Voit conception
of proteid katabolism, should ask wherein lies the value to the body
of this high rate of metabolism of circulating proteid, a rate of
metabolism which is seemingly governed primarily by the amount of
proteid food ingested?
Turning next to Pflüger’s[51] views regarding proteid katabolism, we
find a totally different outlook. Here, the supposition prevails that
the plasma of the blood and lymph, with its contained proteid, is the
food of the organs or their cells, but that before this food material
can undergo katabolism it must first be absorbed by the cell and built
up into the living protoplasm of the tissue. In other words, according
to the views expressed by Pflüger, katabolism must be preceded by
organization of the proteid. Expressed in still different language,
the proteid material circulating in blood and lymph must be eaten up
by the hungry cells and, by appropriate anabolic processes, made an
integral part of the living protoplasm before disassimilation can
occur. Further, according to Pflüger’s conception of these processes,
there is a radical difference in the chemical nature of living
protoplasm as compared with that of the so-called circulating proteid.
The latter is looked upon as being comparatively stable, resisting
oxidation in high degree, and hence not prone to undergo metabolism.
Living protoplasm, on the other hand, is characterized by instability,
suffering oxidation with the greatest ease, and hence readily broken
down in the ordinary processes of katabolism. Assuming for the moment
the correctness of this theory, we see at a glance that all disruption
of proteid matter in the body must be preceded by the upbuilding of the
proteid into living protoplasm. There can be no destruction of proteid
until the latter has been raised to the high plane of living matter.
The dead, inert circulating proteid can serve simply as food for the
living cells, and cannot undergo katabolism until it has been built up
into the organized structure of the tissue or organ. Even though we
grant that a small proportion of proteid may suffer katabolism without
previous organization, it does not materially modify the general trend
of the argument that, according to Pflüger’s hypothesis, proteid
katabolism is essentially a process involving the disruption of living
protoplasm.
[51] Eduard Pflüger: Ueber einige Gesetze des Eiweissstoffwechsels
(mit besonderer Berücksichtigung der Lehre vom sogenannten
“circulirenden Eiweiss”). Archiv f. d. gesammte Physiologie, Band 54,
p. 333.
Consider what this means in the light of facts already presented.
Remembering that the one factor above all others influencing the rate
of proteid katabolism is the amount of proteid food taken in, and that
the output of nitrogen, no matter what the previous condition of the
body or the amount of proteid food ingested, runs more or less parallel
with the consumption of proteid, we are forced to the conclusion, in
accepting this hypothesis, that there must be superhuman activity in
the building up of living protoplasm, only to be followed, however, by
its immediate and more or less complete breaking down. Further, think
of the daily or periodical fluctuation in the construction of bioplasm,
coincident with variations in the amount of proteid food consumed, and
the corresponding destruction of bioplasm as indicated by the daily
output of nitrogen. Imagine, if you will, the concrete case of a man
of 70 kilos body-weight eating a daily ration containing 125 grams
of proteid, the nitrogen equivalent of which is practically excreted
within twenty-four hours, and are we not wise in hesitating to believe
that all of that proteid has been so quickly built up into living or
organized tissue only to be immediately broken down and thrown out of
the body? Think of the enormous activity implied in the manufacture
of this bioplasm in the time allotted, and for what? Apparently, so
that it can be broken down again. But such energy as is liberated in
the breaking-down process might be derived far more economically by
simple destruction of the proteid, as contained in the meshes of the
tissue elements, without assuming a preliminary conversion into living
protoplasm. Obviously, we have here a theory which does not help us in
arriving at any very satisfactory conception of proteid metabolism.
The facts which Pflüger and his followers bring forward in support of
the theory are not very convincing, or at least not sufficiently so to
carry conviction in the face of a natural disinclination to believe in
the necessity of such a profound anabolic process, merely as a prelude
to the speedy destruction of the finished product. Finally, we may add
that if all proteid katabolized in the body must first be raised to the
high level of living protoplasm before the final disruption can occur,
it may be prudent to keep the daily intake of this foodstuff down to a
level somewhat commensurate with the real needs of the body.
As has been stated many times in the course of this presentation,
the most striking feature of proteid metabolism is the rapidity with
which large quantities of proteid consumed as food are broken down,
and the contained nitrogen eliminated from the body as urea. A few
hours will suffice to accomplish the more or less complete destruction
of food proteid; and any theory of proteid metabolism, to be at all
satisfactory, must explain this peculiar phenomenon. According to
recent investigations, it seems probable that some, at least, of the
cleavage products of proteid formed during intestinal digestion are
not built up into new proteid, but are at once eliminated mainly in
the form of urea, without becoming a part of either the so-called
circulating proteid, or the living protoplasm of the body. It will be
recalled that under the influence of the digestive enzymes, trypsin
and erepsin, proteid foodstuffs may be broken down while undergoing
intestinal digestion into monamino- and diamino-acids, such as
leucin, tyrosin, arginin, lysin, etc. A certain proportion of these
comparatively simple substances may be directly absorbed by the
portal circulation and carried to the liver, where they may undergo
conversion into urea. In this way, some portion of the nitrogen of
the ingested food may be quickly eliminated from the system. As has
been stated in another connection, we are not sure at present how
far proteid decomposition of the kind indicated takes place normally
in the body. We merely know that there are present in the intestine,
enzymes capable of splitting up proteid into these small fragments, and
that substances of this type when made to circulate through the liver
are transformed into urea. These facts, coupled with the well-known
tendency of the nitrogen of proteid food to appear in the excretions
a few hours after the food in question has been consumed, naturally
suggests a direct breaking down of proteid along the lines indicated,
with a possible retention of a carbonaceous residue (nitrogen-free)
for subsequent oxidation, as a source of energy for heat or work.
Obviously, all of the proteid food cannot behave in this manner, for
if such were the case there would be no proteid available for making
good the normal waste incidental to tissue changes. Either a certain
amount of proteid escapes this profound alteration produced by the
proteolytic enzymes in question, or else a certain proportion of these
simple decomposition products is synthesized in the intestine, or in
the tissues of the body, to form new proteid for the regeneration of
cell protoplasm. However this may be, we have presented in this view
a plausible explanation of the prompt appearance of food nitrogen in
the excretions, and without compelling belief in a theory, such as
Pflüger’s, which taxes one’s credulity to the utmost. To be sure,
as a prominent writer on physiology has recently said, such a view
stands opposed to our conceptions of the importance of proteid food;
but it seems possible, in the light of accumulating knowledge, that
our conceptions of the part played by proteid foods in the nutrition
of man have not been strictly logical, or quite in accord with true
physiological reasoning.
Again, in this connection, we may ask the question, why is it that the
body provides such an effective method for the speedy breaking down
of proteid food and the prompt elimination of the contained nitrogen?
Whatever the means made use of by the organism in accomplishing this,
the result is the same; the nitrogen of the ingested food is, in large
measure, quickly gotten rid of. We clearly recognize the all-important
position of proteid foods in the nutrition of the body, but there
appears a certain inconsistency in this prompt removal of the
nitrogen-containing portion of the proteid molecule. The nitrogenous
part of the proteid food is, physiologically considered, the
all-important part. It is the only source of nitrogen available to the
system, and yet apparently the larger proportion of this nitrogenous
material is not utilized in any recognizable way, but is eliminated as
quickly as possible. Is it not within the limits of possibility that
these methods, whatever may be the exact mechanism involved, are merely
a means of getting rid of a surplus of proteid for which the body has
no real need? This question I shall try to answer later on in another
connection, but we may advantageously keep this possibility in mind
while we are discussing these theories of proteid metabolism.
It is obvious, in the light of present knowledge, that there must
be a certain amount of true tissue proteid broken down each day,
independent of that larger metabolism coincident with the intake of
proteid food. However much this more voluminous proteid katabolism may
fluctuate, owing to variations in the intake of proteid, and whatever
the significance of this latter phase of metabolism, it is self-evident
that there must be a steady, constant metabolism, upon which the life
of the various tissues and organs of the body depends, and by which
the proteid integrity of the tissue cells is maintained. This implies
a certain degree of true tissue change, in which definite amounts of
proteid material are broken down and the resultant loss made good from
the proteid intake. No matter what specific name be applied to this
form of proteid katabolism, its existence is clearly recognized. It is
obviously a form of metabolism distinct, and probably quite different,
from that form, more variable in extent, which is associated with the
intake of proteid food. Plainly, if there is truth in these statements,
there should be some data available by means of which these two lines
of proteid katabolism can be more or less sharply differentiated.
Thanks especially to the work of Folin,[52] these data are now
apparently at hand, and the facts which he has accumulated with
painstaking care seem destined to throw additional light upon our
conception of proteid metabolism. It will be remembered that in the
breaking down of proteid, the great bulk of its contained nitrogen is
eliminated in the form of urea. In addition, a certain smaller amount
of nitrogen is excreted in the forms of creatinin and uric acid. As
we have seen, the total output of nitrogen, which measures the extent
to which proteid is decomposed in the body, varies with the intake of
proteid food; but it is found that the proportion of nitrogen excreted
in the forms of urea and uric acid varies with the extent of the
metabolism. In other words, quantitative changes in the daily proteid
katabolism are accompanied by pronounced changes in the distribution of
the excreted nitrogen. Let us take a single illustration from Folin’s
results; the case of a healthy man who on one day--July 13--consumed
a proteid-rich diet, and on the other day--July 20--was living on a
diet containing only about 1 gram of nitrogen. The composition of
the excretion through the kidneys on these two days is shown in the
following table:
[52] Otto Folin: Laws Governing the Chemical Composition of Urine.
American Journal of Physiology, vol. 13, p. 66. A theory of Protein
Metabolism. Ibid., vol. 13, p. 117.
+--------------------+-----------------------+---------------------+
| | July 13. | July 20. |
+--------------------+-----------------------+---------------------+
| Volume of urine | 1170 c.c. | 385 c.c. |
| Total nitrogen | 16.80 grams | 3.60 grams |
| Urea-nitrogen | 14.70 " = 87.5% | 2.20 " = 61.7% |
| Uric acid-nitrogen | 0.18 " = 1.1% | 0.09 " = 2.5% |
| Creatinin-nitrogen | 0.58 " = 3.6% | 0.60 " = 17.2% |
+--------------------+-----------------------+---------------------+
Here we see, as would be expected, that on the high proteid diet, there
was a large excretion of total nitrogen and of urea; while on the low
proteid diet, nitrogen and urea were correspondingly diminished. The
point to attract our attention, however, is the marked difference in
the percentage of urea-nitrogen in the two cases; a difference which
amounts to about 26 per cent. A similar difference is to be noted in
the percentage of uric acid-nitrogen. Lastly, it is to be observed that
in spite of the great difference in the extent of metabolism on the
two days--an excretion of 16.8 grams of nitrogen, as contrasted with
3.6 grams--the _amount_ of creatinin-nitrogen is essentially the same.
Folin finds that these peculiarities in the percentage distribution
of excreted nitrogen hold good in all cases where there is this wide
divergence in the amount of proteid katabolized, and, further, that
there is a gradual and regular transition from the one extreme to the
other. He sees in these results evidence that there are in the body
two forms of proteid katabolism, essentially independent and quite
different. One kind is extremely variable in quantity, while the other
tends to remain constant. The variable form has its own particular
kind of waste products, of which urea is the chief. The constant
katabolism, on the other hand, is largely represented by creatinin
and to a lesser degree by uric acid. The more the total katabolism is
reduced, the more prominent become creatinin and uric acid, products
of the constant katabolism; while urea, as chief representative of the
variable katabolism, becomes less conspicuous. Folin suggests the term
_endogenous_ or _tissue_ metabolism for the constant variety, while the
variable form he would name _exogenous_ or _intermediate_ metabolism.
In these suggestions we have not theory only, but a number of very
important facts which plainly must have some significance. Take,
for example, the excretion of creatinin. It is a characteristic
nitrogenous waste product, but its elimination from the body is wholly
independent of quantitative changes in the total amount of nitrogen
excreted. In other words, the amount of creatinin eliminated is a
constant quantity for a given individual under ordinary conditions,
no matter how great the variation in the amount of proteid food,
provided no meat is eaten. Meat must be avoided in testing this point,
since meat contains a certain amount of creatin, or other components,
which would be excreted as creatinin. Further, it is found that every
individual has his own specific creatinin excretion, which fact again
emphasizes the idea that this substance is a product of true tissue
katabolism, having no connection with that variable metabolism, of
which urea is the striking representative. These are facts which cannot
be ignored. They are well established by the careful observations of
Folin, and they are confirmed by a large number of observations made in
our own laboratory. Turn now to that other, more conspicuous, product
of proteid katabolism, urea. With a so-called average proteid intake,
about 88–90 per cent of the excreted nitrogen will be in the form of
urea, but, as Folin states, “with every decided diminution in the
quantity of total nitrogen eliminated, there is a pronounced reduction
in the per cent of that nitrogen represented by urea. When the daily
total nitrogen elimination has been reduced to 3 grams or 4 grams,
about 60 per cent of it only is in the form of urea.” Here, we have the
chief product of exogenous metabolism, a substance quite distinct from
creatinin, just as the process by which it originates is likewise quite
distinct.
Exogenous metabolism is plainly a process of quite a different order
from that of endogenous, or tissue metabolism. The latter involves
oxidation, while the former consists essentially of a series of
hydrolytic cleavages which result in a rapid elimination of the
proteid-nitrogen as urea. In this conception of exogenous katabolism,
we have essentially the same viewpoint as was previously taken in
attempting to explain how excess of proteid food can be so quickly
decomposed, and its nitrogen removed from the body. Whether the
hydrolytic cleavage is accomplished solely by trypsin and erepsin,
whether it takes place only in the intestine and in the liver,
or whether other glands and tissues are involved, is at present
immaterial; the essential point is that we have in the body a variety
of proteid katabolism, quite different from true tissue katabolism, the
extent of which is dependent primarily upon the amount of proteid food
consumed. The process involved is one which aims at the rapid removal
of the proteid-nitrogen as urea; without incorporation of the absorbed
proteid, or its decomposition products, either as an integral or
adherent part of the tissue proteid. Hydrolytic cleavage is eminently
fitted to accomplish this with the least expenditure of energy, while
the carbonaceous residue of the proteid thus freed from nitrogen can be
transformed into carbohydrate, or directly oxidized as the needs of the
body demand.
As one considers these views so admirably worked out by Folin, the
question naturally arises, if the real demands of the body for proteid
food will not be adequately met by the quantity necessary to satisfy
the true tissue metabolism? We may well believe, with Folin, that “only
a small amount of proteid, namely, that necessary for the endogenous
metabolism, is needed. The greater part of the proteid furnished with
so-called standard diets, like Voit’s, _i. e._, that part representing
the exogenous metabolism, is not needed; or, to be more specific, its
nitrogen is not needed. The organism has developed special facilities
for getting rid of such excess of nitrogen, so as to get the use of
the carbonaceous part of the proteid containing it.” In endogenous
metabolism, we have a steady, constant process quite independent of
the amount of proteid food, and absolutely indispensable for the
maintenance of life. So far as we know at present, its representative
creatinin is, for a given individual, the same in amount during
fasting as when a rich, meat-free, proteid diet is taken. The one
factor that seemingly determines the amount of creatinin eliminated is
the weight of the individual, or more exactly the weight of the true
tissue elements of the body, as distinct from fat or adipose tissue.
Endogenous or tissue katabolism obviously calls for a certain quantity
of proteid to maintain equilibrium, but this is small in amount as
compared with the usual intake of proteid foods. The average man, with
his ordinary dietetic habits, consumes more nitrogen than the body can
possibly make use of. The excess is not stored up, “because the actual
need of nitrogen is so small that an excess is always furnished with
the food, except, of course, in carefully planned experiments” (Folin).
We have seen at what low levels of proteid intake, nitrogen equilibrium
can be established, and we may well have faith in the conception of an
endogenous proteid katabolism which involves only minimal quantities of
proteid. Further, we have observed the constant tendency of the body
to maintain a condition of nitrogenous equilibrium, even with varying
income, and how slow the body is to lay by nitrogen on a rich proteid
diet, even when long deprived of proteid food; a fact difficult of
explanation except on the assumption that the real need of the body for
nitrogen is small, and that the tissues habitually carry a relatively
large reserve of nitrogenous material. We may assume with Folin that
“all the living protoplasm in the animal organism is suspended in a
fluid very rich in proteid, and on account of the habitual use of more
nitrogenous food than the tissues can use as proteid the organism
is ordinarily in possession of approximately the maximum amount of
reserved proteid in solution that it can advantageously retain.
When the supply of food proteid is stopped, the excess of reserve
proteid inside the organism is still sufficient to cause a rather
large destruction of proteid during the first day or two of proteid
starvation, and after that the proteid katabolism is very small,
provided sufficient non-nitrogenous food is available. But even then,
and for many days thereafter, the protoplasm of the tissues has still
an abundant supply of dissolved proteid, and the normal activity of
such tissues as the muscles is not at all impaired or diminished. When
30 grams or 40 grams of nitrogen have been lost by an average-sized
man during a week or more of abstinence from nitrogenous food the
living muscle tissues are still well supplied with all the proteid
they can use. That this is so, is indicated on the one hand by the
unchanged creatinin elimination, and on the other by the fact that one
experiences no feeling of unusual fatigue or of inability to do one’s
customary work. Because the organism at the end of such an experiment
still has an abundance of available proteid in the nutritive fluids,
it is at once seemingly wasteful with nitrogen when a return is made
to nitrogenous food. This is why it only gradually, and only under
the prolonged pressure of an excessive supply of food-proteid again
acquires its original maximum store of this reserve material.”
We may reasonably suppose that the reserve of proteid present in the
body is contained in the fluid media, and not as a part of the living
protoplasm. Further, we are apparently justified in the belief that
the sole form of proteid katabolism which is vitally important for the
welfare of the body is the endogenous katabolism. This must be provided
for adequately and indeed liberally, and in addition there should be
sufficient intake to keep up an abundant supply of reserve proteid, but
beyond these necessities there would seem to be no legitimate demand
for additional proteid. The voluminous exogenous proteid katabolism so
conspicuous in most individuals would seem to have no justification
in fact, or in physiological reasoning. What good, for example, can
be accomplished by this constant splitting off of nitrogen, with its
subsequent speedy removal from the body? The organism can neither use
it nor store it up, and why therefore should this daily burden of an
excessive and accelerated proteid katabolism be borne? As we have seen,
the energy of muscle work is derived mainly, and can come wholly, from
the breaking down of non-nitrogenous materials, fats and carbohydrates.
The very fact that an intake of say 120 grams of proteid is followed
at once by the removal of the larger part of the contained nitrogen,
as a result of the exogenous katabolism of the body, would seemingly
warrant the view that the proteid so decomposed might advantageously be
replaced by a corresponding amount of carbohydrate. In muscle work, as
in heat production, carbohydrate and fat are the materials burned up,
or oxidized. Proteid, on the other hand, is not so oxidized, at least
not the nitrogen-containing portion of the molecule.
There are apparent only two possible reasons for assuming a need on
the part of the body for the high exogenous katabolism of proteid so
commonly observed. The one is that the carbonaceous residue left after
the cleavage of nitrogen from the proteid molecule is better adapted
for the needs of the body than either carbohydrate or fat. Although
this does not seem very probable, it is of course a possibility and
merits consideration. Feeding experiments, with a comparatively small
proteid intake, continued over a sufficient length of time, would show
conclusively how much weight should be attached to this hypothesis. The
other possibility is that the body may derive some advantage from the
presence, in the tissues and fluids, of the varied nitrogenous cleavage
products split off from proteid so abundantly in exogenous katabolism.
These substances are mainly amino-acids on their way to urea, and there
is no apparent reason why they should be of service to the organism.
Still, the processes going on in the tissues and organs of the body are
intricate and not wholly understood, and we can conceive of some useful
function of which as yet we have no knowledge. In the construction of
tissue proteid, for example, as in a possible synthesis out of the
fragments formed by hydrolytic cleavage, it is not impossible that
certain corner-stones are needed, and that in order to obtain these
there must be a more or less wasteful breaking down of food-proteid.
However improbable this may seem, it, like the preceding hypothesis,
can be tested in a way by adequate feeding experiments, which shall
determine the effect on the body of a low proteid intake continued over
a long period of time. On the other hand, it is equally plausible, and
for some reasons more probable, to assume that this excessive exogenous
katabolism may be in a measure prejudicial to the best interests of the
body; that the many nitrogenous fragments formed in the efforts of the
organism to prevent undue accumulation of reserve proteid may in the
long run do as much harm as good.
Further, there is reason in the question whether the continual carrying
of excessive amounts of nitrogen reserves in the shape of soluble
proteid in the blood and lymph, and in the meshes of tissue and cell
protoplasm, is advantageous for the maintenance of the highest degree
of efficiency? We all recognize that an excessive accumulation of fat
is distinctly disadvantageous to the welfare of the body, and there
is, physiologically speaking, equally good ground for considering that
the storage of unorganized proteid in amounts beyond all possible
requirements of the body may be equally undesirable. Because less
tangible to the eye, the accumulation of unnecessary proteid is not
so easily recognizable, but this fact does not diminish the possible
danger which such accumulation may constitute. It must be granted,
however, that we are dealing here with hypotheses and not facts, but
though hypothetical the suggestions made are of sufficient moment to
merit attention and experimental study. In a later chapter, we shall
have occasion to present some facts bearing on these questions.
In the meantime, we may lay due stress upon the significance of these
views regarding proteid katabolism. We must accept as settled the
general idea that there are two distinct forms of proteid katabolism
within the body; one form representing the decay of tissue or cell
protoplasm, small in amount, with its own particular decomposition
products, and absolutely essential for the continuance of life.
The other form, the so-called exogenous katabolism, runs a totally
different course with distinctive side-products and end-products; it
is variable in extent, in harmony with variations in proteid intake,
and subject to the suspicion that at the level ordinarily maintained
it constitutes a menace to the preservation of that high degree of
efficiency which is an attribute of good health.