METABOLISM. - The term m. denotes the whole set of chemical transformation processes that the materials introduced from the environment (ingesta) undergo in their flow through organisms.
Limiting ourselves to considering only animal organisms, these materials are represented, besides by oxygen, water and mineral salts, also by organic substances which, for the most part, consist of the three fundamental food principles: carbohydrates, lipids and proteins. All these substances, after their utilization, are returned to the environment, more or less modified (excreta).
With the organic food principles, animals induce also a certain amount of chemical energy, which is contained in them and which is the only form of energy available to them, unlike plants, which in their m. also have at their disposal the radiant luminous energy of the sun.
Comparing the ingesta and the excreta, one observes that the organic substances introduced by animals are for the most part eliminated in a much simpler chemical form; the carbohydrates and lipids in the form of water and carbon dioxide, the proteins also as urea, uric acid, creatine, etc. Now, from the energetic point of view, the excreta are either completely devoid of chemical energy (H₂O, CO₂), or the residual chemical energy that still remains in them, as in the case of urea, is much lower than the energy content of the food principles from which they are derived.
In m. one distinguishes first of all a preliminary phase, the digestive phase, in which the ingesta introduced are chemically modified in the digestive tract so as to become absorbable.
The proteins, during the processes of digestion, while they are transformed into quite simple substances (amino acids) that are easily absorbed, simultaneously lose their character of specificity, that is, there are erased in them the markers that every protein retains of the animal or plant species from which it comes. The digestive phase is then followed by the phase of intermediate m., in which the various chemical substances that have penetrated into the cells of the individual tissues are, through complex chemical processes, used by these for the performance of their specific functions. These materials that the cells use are represented by the substances absorbed from the intestine, by the products prepared by certain organs to be further processed by other organs, and by the oxygen released by the blood; taken together they are called anabolites. Finally there is the terminal phase of m., which consists in the elimination of the end products of intermediate m., which, no longer being used (catabolites), must be returned to the external environment. The totality of the anabolites and catabolites is collectively called metabolites.
The chemical processes that take part in the digestive phase of m. consist in hydrolytic cleavages of the bonds between carbon and oxygen and between carbon and nitrogen present in the organic food principles. In these processes of hydrolytic simplification there is little release of energy, because the products of digestion have almost the same energy content as the original food principles. On the other hand, the complex chemical processes of intermediate m. are characterized by very profound chemical modifications, because a considerable number of such processes consists in the cleavage of the carbon-carbon bonds of the anabolites; with this there is destruction of the carbon skeleton of the organic substances and more or less complete release of the chemical energy contained in them.
These demolitions during intermediate m. are in general due to processes of oxidation. When the oxygen that the blood carries to the cells takes part in these demolitions, one arrives at the formation of extremely simple end products (water and carbon dioxide) with total release of the chemical energy. The complex of the cleavages that are accomplished in intermediate m. with the participation of oxygen constitutes the so-called cellular respiration. During intermediate m., demolitions of the anabolites can also occur in the absence of oxygen (anoxidative cleavages). In this case the demolitions are less profound and the quantity of chemical energy set free is smaller. The totality of the anoxidative cleavages of intermediate m. constitutes what is commonly called fermentation. Oxidative and anoxidative cleavages do not mutually exclude each other. Often the former are preceded by the latter. In muscle, for example, the cleavage of glycogen down to the end products CO₂ and H₂O is completed by the participation of oxygen after the demolition of glycogen had already been begun by means of a series of intermediate anoxidative demolitions (glycolysis).
However, one should not believe that intermediate m. consists only of processes of cleavage; these, at least in animals, are only prevalent, but alongside them there also occur complex processes of synthesis, which are necessary for the construction of protoplasms during growth and for the repair of their wear during the exercise of their functions. Processes of synthesis are also made necessary for the elaboration of the products of internal and external secretions. In these processes of synthesis and reconstruction, chemical energy is consumed which, in a more or less considerable quantity, is accumulated in the products of the syntheses; and, since m. too is subject to the law of conservation of energy, the energy necessary for the carrying out of processes of synthesis is obtained by using part of that released during the contemporaneous metabolic processes of cleavage.
For the study of intermediate m., besides knowledge of the initial and final chemical substances of m. itself, one also needs knowledge of the various intermediate chemical substances, into which a given food principle is transformed before being eliminated. This is the most arduous task for the biochemist, because the products of intermediate m. are prepared and elaborated in the microscopic, complex and delicate cellular chemical laboratory, and not only that, but because the successive transformations of these products are often very rapid, many of them being represented by unstable or in any case highly reactive substances. Nevertheless, knowledge of intermediate m. has become much deeper in the last twenty years. The vertiginous development of a branch of biochemistry, enzymology, contributed to this, more than the considerable refinement of research techniques, and the progress of knowledge of intermediate m. was subordinate to that development. In fact, once very numerous enzymes had been isolated and once the constitution of the active part of many of them (coenzymes) was known, it became possible to establish, in several cases, also the mechanism of action of the enzymes and the way in which they are coordinated in their action. And since enzymes are the tools that cells use in carrying out their metabolic work, the biochemist, thanks to the developments of enzymology, came into possession of these very tools and was able to employ them under suitable experimental conditions. The use of isotopes has also contributed to the great modern development of current knowledge of intermediate m. By administering to an animal a substance — which may be a given food principle or a supposed intermediate product of its m. — into which, by suitable syntheses, a stable isotope (H², N¹⁶, C¹²) or a radioactive isotope (C¹⁶, P³², S³², J¹²⁸) has been introduced, this substance thus labeled can be followed in its metabolic transformations and in its wanderings through the organism until its elimination. The isotope method has the advantage of allowing one to work on animals under physiological conditions and not only on isolated organs, or on fragments or extracts of organs, as had generally been done previously.
The rapid, fundamental conquests of biochemistry in the field of intermediate m. made themselves felt immediately also in pathology, shedding light on the etiology of many diseases of metabolism, which previously appeared completely obscure, in physiology, clarifying the chemistry that underlies every function, and in pharmacology, facilitating the interpretation of the mechanism of action of many drugs.