It appears then that the cells of the body are offered protein of a constant form, that of the serum albumin and serum globulin of the blood and lymph. It is possible, and even probable, that a second process of digestion now takes place and that the cell breaks down their material and rebuilds it into its own tissue. It is also possible that some aminoacids are conveyed by the blood directly to the cells, and that the cells select what they require.
Lastly, we must inquire by what means the constant disintegration of living tissue is carried out. If an organ taken from the body be kept under aseptic conditions it undergoes a chemical dissolution known as autolysis, and the products found are similar to those obtained by the hydrolysis of protein in other ways. This liquefaction is attributed to ferment action. It is probable that the removal of inflammatory products, such as the exudation into the pulmonary alveoli in pneumonia, takes place by this means. But even in the healthy body portions of cells are always dying and there is a good deal of evidence to show that this normal disintegration of tissue is also due to enzymes and is analogous to or even identical with the autolytic action observed after death. The blood serum appears to contain an anti-ferment inhibiting this action, and may be supposed to prevent a too general autolysis. On such a view the anabolism and the katabolism of the tissues is the result of antagonistic ferment actions the balancing of which results in perfect health.
The aminoacids formed by the breaking down of cells are carried to the liver, where their nitrogen is converted into urea and excreted, probably in just the same way as the surplus nitrogen from the food is got rid of immediately after its absorption. A proportion of the nitrogen of the urine, however, is not in the form of urea but of uric acid and other purin bodies, and of ammonia and creatinine. These nitrogenous substances, especially the creatinine and uric acid, result from cell metabolism or the metabolism of structure, and, with part of the urea, represent the " endogenous " metabolism of nitrogen. The remainder of the urea is regarded as derived from the nitrogen of the protein which is rapidly excreted, and may be called exogenous.
The special metabolism of purin bodies will be reviewed in another part of this volume.
The creatinine in the urine has generally been regarded as mainly derived from muscle, and although some doubt has been thrown upon this, the writer has brought forward pathological evidence supporting the original view, having confirmed the observation, made long ago, that in muscular atrophies the excretion of creatinine is greatly diminished.
The fat absorbed in the intestine and passed into the thoracic duct is carried into the general circulation, and, if not at once needed for oxidation, is deposited in connective tissue cells in the fat depots of the body, especially in the subcutaneous tissue, in the omentum and around the kidneys. The fat stored in this way is of the same kind as that in the food. This has been shown by feeding animals upon special forms of fat, which have then been recognized in the tissues either by their melting points or by their powers of combining with iodine, which differ in different fats. Hence fat is deposited without undergoing any fundamental assimilative change. This is the direct opposite to what we have seen occurs with protein. The two cases are not, however, really analogous, for the depot fat cannot be regarded as actually forming part of the living tissues; and we shall see later that when fat is built up into tissues there is evidence that it undergoes considerable change. This deposited fat is used in lactating animals to furnish the fat of the milk, for the melting point of butter may be definitely altered by feeding a cow upon cotton seed oil or palm oil. Again if much linseed oil be given the milk will be of an oily nature; and sesame and almond oil have been shown to be present in the butter fat of a cow fed upon these foods. The fat of the sebaceous glands is also identical with that ingested.
The fat in the body, besides being derived from that in the food, may be formed from carbo-hydrate as was first proved by Lawes and Gilbert. In the formation of fat from carbo-hydrate we should expect that an excess of C02 would be liberated, which would appear in the expired air, and as a matter of fact a rise of the respiratory quotient above unity has been observed in man and animals fed, after fasting, upon an abundant carbohydrate diet (Hanriot, Pembrey). In the vegetable kingdom oils are of course synthesized and probably from carbo-hydrate. The steps of such a transformation are not yet worked out, but we may mention that sugar, under the influence of a ferment, can easily give rise to lactic acid, and that the liver appears to have the power of forming butyric acid, which is a lower member of the fatty acid group, from lactic acid. Experimentally, also, some of the lower fatty acids can be synthesized from bodies of a carbo-hydrate nature (Harden).
The evidence for the formation of fat from protein is conflicting; it was formerly thought that protein could form fat, but a repetition of the old experiments has undermined a good deal of the evidence. For instance, in the case of animals fed for long periods upon protein only it had been found that fat was laid on, but it has since been pointed out that the small amount of fat remaining among the fibres of the meat given as food was sufficient to account for this. Again, the large droplets of fat which are to. be seen in osmic acid preparations of the liver in phosphorus poisoning were taken as evidence of fatty degeneration, the fat being regarded as formed from the protein of the cells. This conclusion was not, however, justified, for in the first place the microscopical evidence of fat is an unsafe guide to the actual quantity present, as there may be less fat in a tissue which is apparently full of it than in a normal organ showing none in the form of droplets : secondly, the fat contained in such a poisoned liver has been shown by Rosenfeld to be derived, not from the liver, but from the connective tissue; in the case, for example, of a dog first fed on mutton fat and then poisoned with phosphorus it was found that the fat in the liver was mutton fat. In an organ, then, which shows fatty infiltration the fat is not necessarily formed from the protoplasm of the organ but may accumulate in droplets because the poisoned cells are unable to utilize that which is brought in the blood.
The changes which take place when fat is oxidized are imperfectly understood. Although fat may be deposited in the tissues, and even excreted in the milk unchanged, recent work by Leathes and by Hartley suggests that it undergoes important assimilative changes before it is finally oxidized to furnish energy. The fats isolated from active organs such as the heart and the liver have a higher iodine value (that is contain less hydrogen) than those in the food. The iodine value of connective tissue fat, for instance, is 64; the fat of a degenerated liver has a value of 70; but that of a normal liver has a value of 120. It is probable, therefore, that the ordinary fats are transformed in the tissues into more complex substances, of which lecithin may serve as a type; and several lecithin-like bodies of great complexity have been found in the heart muscle. The study of these will probably yield information as to the mode of utilization of fat.
When fat is burnt in the body the respiratory quotient is low, for much of the oxygen taken in is required to oxidize the large amount of hydrogen which fats contain and this oxygen is excreted as water and does not appear in the expired air, with the consequence that the ratio CO2/O2 is depressed below unity, its theoretical value under these circumstances being .7. The oxidation of protein gives a respiratory quotient of .8, whilst if carbo-hydrate is alone being used the quotient observed should be unity.