THE SPECIFIC DYNAMIC ACTION OF PROTEIN AND AMINO ACIDS IN ANIMALS

Summary When food is ingested by an animal in an environmental temperature above 25°C. his energy metabolism increases. This is known as the specific dynamic action of foodstuffs. The largest specific dynamic action is exerted by protein and amino acids. The specific dynamic action of injected amino acids, other things being equal, is approximately the same as protein taken by mouth. This and other evidence exclude the work of digestion and absorption as the source of this increase in metabolism. The other of the older hypotheses proposed in explanation of this phenomenon referred the increased heat production and respiration to an increased metabolism of the cells, apart from digestion, absorption and excretion. That of Voit was that the increased metabolism was a plethora effect, the result of an increased concentration of metabolites in the cell; of Rubner that the increased heat production represented reactions in which part of the protein was converted to glucose, the remainder not convertible to glucose is burned with the nitrogen-carrying moiety. The heat produced in these reactions, according to Rubner, is not utilisable by the organism and hence appears only as heat. Lusk restated these hypotheses in terms of specific chemical reactions and subjected them to experimental test. He first took the position that though the increased metabolism following the ingestion of carbohydrate and fat were plethora effects, the calorigenic effect of amino acids was of different origin and represented a specific stimulation of the cells without the amino acids themselves necessarily undergoing oxidation. Later he modified this view and held that the specific dynamic action of amino acids represented the heat loss in converting the deaminised residues to glucose, and this specific dynamic effect was an absolute and characteristic constant for each amino acid, in spite of the fact that his observations, as a rule, terminated long before the metabolism of the amino acid administered was complete. Lusk held also that the metabolism of the nitrogen—deamination, urea formation, and excretion—was not responsible for any of the increase in metabolism observed. This contention was based mainly on the observation that glutamic acid exerts no specific dynamic effect, an observation which all other observers have shown to be erroneous. Lusk's explanation fails to account for the large specific dynamic effects of amino acids, such as tyrosine and phenylalanine, which are not converted to glucose. Although it was emphasised by Lusk (at first at any rate) that the increase in energy metabolism is proportional to the amount of protein or amino acid metabolised, the practice arose, particularly among clinical workers, of considering the increase in energy metabolism observed in the first few hours as an absolute quantity to be referred to the quantity of protein or amino acid administered, rather than to the quantity metabolised in the interval through which the energy metabolism was observed. This is chiefly responsible for the conflicting reports regarding variations in the specific dynamic action of protein in endocrine and nutritional disorders. The specific dynamic action of protein is not constant. It is usefully expressed as a ratio of calories in excess of the basal to urinary nitrogen in excess of the basal. Nearly all the data on record which can be expressed in this form are collected. A theory of the specific dynamic action of protein is presented which accounts for the variations, and the minimum and maximum values observed for the ratio of excess calories to excess urinary nitrogen. According to this theory the specific dynamic action is a composite of two factors, one nearly constant, representing the increased energy production attending the metabolism and excretion of the nitrogen, and amounts to 7–10 calories per gram of nitrogen; the other—more variable, and at times larger fraction—arises from the metabolism of the carbon. Since the amino acids do not act as primary stimulants to cellular metabolism (the evidence for this is discussed in detail) the increase in metabolism follows their deamination—hence the parallel between the increase in energy metabolism and the increased concentration of amino acids in the blood, the increased urinary excretion of uric acid in man, and of glucose in the phlorhizinised dog. For the same reason when the organs in which deamination occurs are removed—the liver, and to a lesser extent the kidneys and small intestine—injected amino acids exert no specific dynamic action; and in the normal animal the specific dynamic action is confined to the viscera. In the metabolism of the nitrogen, the heat produced in oxidative deamination is not available to the organism for work because the stoichiometrical requirements when oxygen combines directly with a metabolite must be satisfied. For the same reason in the coupled reactions whereby urea and other products (glycogen) are synthesised, the excess energy is not available for physiological work. The metabolism of the carbon is responsible for the observed variations in the specific dynamic action of protein. In general it may be compared to the recovery phase of muscular exercise. An oxygen debt is incurred, and the cost of its repayment varies with the nutritional state and the nature and fate of the deaminised residue. Accordingly the specific dynamic action of protein is not available for muscular or other work in the organism. It will vary according to the extent that the deaminised residues spare tissue carbon, whether they are converted to glucose or fat, and according to the nature of the fuel mixture supporting these syntheses and conversions. This theory accounts for most of the hitherto anomalous phenomena in the specific dynamic action of protein. Reference of the increase in metabolism to the quantity of nitrogen metabolised shows that there is no “neutralisation” of the specific dynamic effects of amino acids when these are given with protein; and the specific dynamic action of protein is not particularly low or absent in endocrine or nutritional disorders. Analysis of the physiology of coupled reactions, taking into account the mode of deamination of individual amino acids (whether oxidative or hydrolytic), and the nature of the deaminised residue indicates the reasons for the high specific dynamic effects of ketogenic amino acids such as tyrosine and phenylalanine, and of glutamic acid, and also for certain possible low figures, as in the cases of arginine and histidine.