METABOLISM. – Metabolism is called the sum of the chemical transformation processes that the materials introduced from the environment (ingesta) undergo as they pass through organisms.
Limiting ourselves to considering only animal organisms, these materials consist, in addition to oxygen, water, and mineral salts, of organic substances, most of which are composed of the three fundamental nutritional principles: carbohydrates, lipids, and proteins. All these substances, after their utilization, are returned to the environment in a more or less modified form (excreta).
With the organic nutritional principles, animals also introduce a certain amount of chemical energy, which is contained within them and is the only form of energy available to them, unlike plants, which in their metabolism also have access to the radiant luminous energy of the sun.
By comparing the ingesta and the excreta, it is observed that the organic substances introduced by animals are largely eliminated in a much simpler chemical form; carbohydrates and lipids in the form of water and carbon dioxide, proteins also as urea, uric acid, creatine, etc. Now, from an 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 much less than the energy content of the nutritional principles from which they are derived.
In metabolism, a preliminary phase is first distinguished: the digestive phase, in which the ingested materials are chemically modified in the digestive tract so as to become absorbable.
During the digestive processes, proteins are transformed into very simple substances (amino acids) that are easily absorbed, while simultaneously losing their specific character; that is, the distinctive marks that each protein retains from the animal or plant species from which it originates are erased. Following the digestive phase is the intermediate metabolism phase, in which the various chemical substances that have entered the cells of individual tissues are utilized through complex chemical processes for the performance of their specific functions. The materials that the cells utilize consist of substances absorbed from the intestine, products prepared by certain organs to be further processed by other organs, and oxygen released by the blood; collectively, these are called anabolites. Finally, there is the terminal phase of metabolism, which consists in the elimination of the final products of intermediate metabolism, which, no longer being utilized (catabolites), must be returned to the external environment. The sum of anabolites and catabolites is collectively referred to as metabolites.
The chemical processes involved in the digestive phase of metabolism consist of hydrolytic cleavages of the bonds between carbon and oxygen and between carbon and nitrogen present in the organic nutritional principles. In these processes, there is little energy release because the digestion products have almost the same energy content as the original nutritional principles. Instead, the complex chemical processes of intermediate metabolism are characterized by profound chemical changes, because a considerable number of these processes involve the cleavage of carbon-carbon bonds in anabolites; this results in the destruction of the carbon skeleton of organic substances and the more or less complete release of the chemical energy contained within them.
These breakdowns during intermediate metabolism are generally due to oxidation processes. When oxygen, which the blood carries to the cells, participates in these breakdowns, extremely simple final products are formed (water and carbon dioxide) with the total release of chemical energy. The complex of cleavages that occur in intermediate metabolism involving oxygen constitutes the so-called cellular respiration. During intermediate metabolism, breakdowns of anabolites can also occur in the absence of oxygen (anoxidative cleavages). In this case, the breakdowns are less profound and less chemical energy is released. The sum of the anoxidative cleavages of intermediate metabolism constitutes what is commonly called fermentation. Oxidative and anoxidative cleavages do not exclude each other. Often, the former are preceded by the latter. In muscle, for example, the cleavage of glycogen into the final products CO₂ and H₂O is completed by the participation of oxygen after the breakdown of glycogen had already been initiated through a series of intermediate anoxidative cleavages (glycolysis).
However, it should not be thought that intermediate metabolism consists solely of cleavage processes; these, at least in animals, are only prevalent, but alongside them there also occur complex synthesis processes, which are necessary for the construction of protoplasm during growth and for the repair of wear during the exercise of their functions. Synthesis processes are also necessary for the elaboration of the products of internal and external secretions. In these synthesis and reconstruction processes, chemical energy is consumed, which, to a greater or lesser extent, is stored in the products of synthesis; and, since metabolism is also subject to the law of the conservation of energy, the energy required for synthesis processes is obtained by utilizing part of that released during the simultaneous metabolic cleavage processes.
For the study of intermediate metabolism, in addition to knowledge of the initial and final chemical substances of the metabolism itself, it is also necessary to understand the various intermediate chemical substances into which a given nutrient principle is transformed before being eliminated. This is the most arduous task for the biochemist, because the products of intermediate metabolism are prepared and processed in the microscopic, complex, and delicate chemical laboratory of the cell, and also because the subsequent transformations of these products are often extremely rapid, as many of them consist of unstable or highly reactive substances. Nevertheless, knowledge of intermediate metabolism has greatly deepened in the last two decades. More than the notable improvement in research techniques, this has been due to the dizzying development of a branch of biochemistry, enzymology, upon which progress in the understanding of intermediate metabolism depended. Indeed, once numerous enzymes had been isolated and the structure of the active part of many of them (coenzymes) was known, it became possible in many cases to establish the mechanism of enzyme action and how they are coordinated in their activity. And since enzymes are the tools used by cells in carrying out their metabolic work, the biochemist, thanks to developments in enzymology, has come into possession of these same tools and has been able to employ them under suitable experimental conditions. The great modern advances in current knowledge of intermediate metabolism have also been aided by the use of isotopes. By administering to an animal a substance—whether a specific nutrient principle or a supposed intermediate product of its metabolism—in which, through appropriate syntheses, a stable isotope (H, N¹⁴, C¹³) or a radioactive isotope (C¹⁴, P³², S³³, J¹³¹) has been introduced, this labeled substance can be traced through its metabolic transformations and its distribution in the organism until its elimination. The isotope method has the advantage of allowing experiments to be conducted on animals under physiological conditions, rather than solely on isolated organs, tissue fragments, or organ extracts, as had generally been done previously.
The rapid, fundamental advances in biochemistry regarding intermediate metabolism have immediately impacted pathology, shedding light on the etiology of many metabolic diseases that previously appeared completely obscure; in physiology, clarifying the chemistry underlying every function; and in pharmacology, facilitating the interpretation of the mechanism of action of many drugs.