METABOLISM. – The term m. denotes the ensemble of chemical transformation processes that the materials introduced from the environment (ingesta) undergo in their passage through organisms.
If we limit ourselves to considering animal organisms alone, these materials are represented, in addition to oxygen, water, and mineral salts, also by organic substances which, for the most part, consist of the three fundamental nutritive principles: carbohydrates, lipids, and protids. All these substances, after their utilization, are returned to the environment, more or less modified (excreta).
(Alinari photograph) MESSINA — Remains of the Church of the Nunziatella de' Catalani (12th century) — Messina.
Comparing the ingesta and the excreta, one finds that the organic substances introduced into animals are for the most part eliminated in a much simpler chemical form: carbohydrates and lipids in the form of water and carbon dioxide, and proteins also in the form of urea, uric acid, creatine, etc. From the energetic point of view, the excreta are either completely devoid of chemical energy (H₂O, CO₂), or the residual chemical energy still present in them, as in the case of urea, is far less than the energy content of the nutrients from which they derive.
In metabolism, one distinguishes first of all a preliminary phase, the digestive phase, in which the introduced ingesta are chemically modified in the digestive tract so as to become absorbable.
During the processes of digestion, proteins are transformed into very simple substances (amino acids) that are easily absorbed; at the same time, they lose their specific character—that is, the identifying marks that each protein retains of the animal or plant species from which it originates are erased. The digestive phase is followed by the phase of intermediate metabolism, in which the various chemical substances that have penetrated into the cells of the individual tissues are utilized by those cells, through complex chemical processes, for the performance of their specific functions. These materials utilized by the cells consist of substances absorbed from the intestine, products prepared by certain organs for further processing by other organs, and oxygen released by the blood; taken together, they are called anabolites. Finally, there is the terminal phase of metabolism, consisting in the elimination of the end products of intermediate metabolism which, no longer being utilized (catabolites), must be returned to the external environment. The totality of anabolites and catabolites is collectively termed metabolites.
The chemical processes occurring during the digestive phase of metabolism consist in the hydrolytic cleavage of the bonds between carbon and oxygen and between carbon and nitrogen present in organic nutrients. These processes of hydrolytic simplification involve little liberation of energy, because the products of digestion have almost the same energy content as the original nutrients. By contrast, the complex chemical processes of intermediate metabolism are characterized by very profound chemical modifications, since a considerable number of them consists in the cleavage of the carbon–carbon bonds of anabolites; this entails destruction of the carbon skeleton of the organic substances and the more or less complete liberation of the chemical energy contained in them.
These breakdowns during intermediate metabolism are generally due to oxidation processes. When oxygen carried by the blood to the cells participates in these breakdowns, extremely simple end products (water and carbon dioxide) are formed, with total liberation of chemical energy. The complex of cleavages occurring in intermediate metabolism with the participation of oxygen constitutes what is known as cellular respiration. During intermediate metabolism, breakdowns of anabolites may also occur in the absence of oxygen (anoxidative cleavages). In this case the breakdowns are less profound, and the quantity of chemical energy released is smaller. The totality of the anoxidative cleavages of intermediate metabolism constitutes what is commonly called fermentation. Oxidative and anoxidative cleavages do not mutually exclude one another. The former are often preceded by the latter. In muscle, for example, the cleavage of glycogen into the final products CO₂ and H₂O is completed through the participation of oxygen after the breakdown of glycogen has already been initiated by means of a series of intermediate anoxidative breakdowns (glycolysis).
It should not be thought, however, that intermediate metabolism consists solely of cleavage processes; these, at least in animals, are merely predominant, while alongside them there also occur complex synthetic processes, which are necessary for the construction of protoplasm during growth and for the repair of wear and tear sustained by it in the exercise of its functions. Synthetic processes are also necessary for the elaboration of the products of internal and external secretions. In these processes of synthesis and reconstruction, chemical energy is consumed and, in more or less considerable quantities, accumulated in the products of synthesis; and since metabolism too is subject to the law of the conservation of energy, the energy required for the performance of synthetic processes is obtained by using part of that liberated during the simultaneous metabolic processes of cleavage.
For the study of intermediate metabolism, in addition to knowledge of the initial and final chemical substances involved in metabolism itself, it is also necessary to know the various intermediate chemical substances into which a given nutrient is transformed before being eliminated. This is the most arduous task facing the biochemist, not only because the products of intermediate metabolism are produced and processed in the microscopic, complex, and delicate chemical laboratory of the cell, but also because the successive transformations of these products are often extremely rapid, many of them being unstable or otherwise highly reactive substances. Nevertheless, knowledge of intermediate metabolism has deepened considerably over the past twenty years. This has been contributed to less by the considerable refinement of research techniques than by the dizzying development of a branch of biochemistry, enzymology, upon which the advancement of knowledge of intermediate metabolism depended. Indeed, once very numerous enzymes had been isolated and the constitution of the active portion of many of them (coenzymes) had become known, it was possible to establish, in many cases, both the mechanism of enzyme action and the manner in which the enzymes are coordinated in their action. Since enzymes are the instruments used by cells in carrying out their metabolic work, the biochemist, through the developments of enzymology, came into possession of these very instruments and was able to employ them under suitable experimental conditions. The use of isotopes also contributed to the great modern development of present knowledge of intermediate metabolism. By administering to an animal a substance—which may be a particular nutrient or a presumed intermediate product of its metabolism—in which, by means of suitable syntheses, a stable isotope (H², N¹⁶, C¹²) or a radioactive isotope (C¹⁶, P³², S³², J¹²⁸) has been introduced, this labeled substance can be followed through its metabolic transformations and its movements within the organism up to its elimination. The isotope method has the advantage of making it possible to work with animals under physiological conditions, rather than only with isolated organs, or fragments or extracts of organs, as had generally been done previously.
The rapid and fundamental advances of biochemistry in the field of intermediate metabolism immediately made themselves felt in pathology as well, shedding light on the etiology of many diseases of metabolism that had previously appeared completely obscure; in physiology, by clarifying the chemistry underlying every function; and in pharmacology, by facilitating the interpretation of the mechanism of action of many drugs.