Biochemistry of Amino Acids - A. Majster 1961

General Biochemistry and Physiology of Amino Acid Metabolism
Metabolism of the Amino Group
Dynamic State of Amino Acids and Proteins

The existence of active enzyme systems for deamination and reamination in mammals was conclusively demonstrated in experiments on rats administered N¹⁵-ammonium and N¹⁵-Amino Acids. In the classical works of Schoenheimer and his co-workers [73–80], it was discovered that administering N¹⁵ to rats (in the form of ammonium salts or amino acids) leads to the appearance of the isotopic label in Almost all amino acids. It was established that the tissue concentration of the isotope is generally highest in The amino acid administered to the animal, followed in order of decreasing isotope concentration by glutamic and aspartic acids.

After feeding N¹⁵-aspartic acid, the highest concentration of the isotope is found in glutamic acid isolated from tissue Proteins. The high concentration of the isotope in dicarboxylic amino acids is in good agreement with the high rate of Transamination of these Amino Acids and with data on the incorporation of ammonia nitrogen into glutamic acid under the action of Glutamate dehydrogenase. The fact that the highest concentration of the isotope is found in glutamic acid after feeding animals N¹⁵-aspartic acid is consistent with the widespread occurrence and high activity of glutamate-aspartate transaminase. The studies of Schoenheimer and his colleagues also showed that, although N¹⁵-amino acids administered per os can serve as direct precursors of the corresponding protein amino acids, they are diluted in the Organism by identical amino acids already present therein.

Before Schoenheimer's work, Folin [81] proposed The Theory of "exogenous" and "endogenous" METABOLISM. This theory assumed the existence of Two Types of Nitrogen metabolism. In one of them (exogenous), which depends on dietary composition, the main end product was urea. In endogenous metabolism, which, according to Folin, proceeds independently of dietary influence, creatinine was considered one of the characteristic nitrogenous end products. Folin regarded endogenous Metabolism as a manifestation of body tissue "wear and tear." The data of Schoenheimer and his co-workers were inconsistent with Folin's concept; on the contrary, they supported the views of Borsook and Keighley [82] on "continuous metabolism." Schoenheimer's isotopic studies showed that tissue Amino Acids and Proteins are in a dynamic state under conditions of both positive and negative nitrogen balance.

In one of the studies, rats were administered the heavy nitrogen isotope in the form of D-leucine; The amount of N¹⁵ incorporated into proteins was approximately the same as in the case of animals fed N¹⁵-L-leucine. Upon administration of deuterium-labeled D-leucine, a certain amount of deuterium was found in tissue L-leucine, indicating a partial Conversion of the carbon Skeleton of D-leucine into L-leucine; this transformation implies the inversion of the configuration of the a-carbon atom. The results of the mentioned experiments are of interest in connection with data indicating the impossibility of replacing L-leucine with D-leucine in Nutrition (growth studies in young rats). Evidently, The conversion of D-leucine to L-leucine proceeds at a rate insufficient to support animal growth. Apparently, D-Amino acids are deaminated by D-Amino Acid Oxidase to form the corresponding a-keto acids, and the latter undergo transamination, turning into the corresponding L-amino acids.

Two amino acids—Lysine and Threonine—occupy a special position in nitrogen metabolism, as N¹⁵ introduced into animals as ammonia or Other Amino Acids is not incorporated into them in noticeable amounts. After feeding animals deuterium- and N¹⁵-labeled lysine, the isotopic nitrogen was found in other amino acids; however, in lysine isolated from tissue proteins, The ratio of deuterium to N¹⁵ concentrations was almost the same as in the administered lysine [83, 84]. Similar results were obtained with threonine [85].

Schoenheimer's observations formed The basis of the concept that dietary amino acids are in equilibrium with the "metabolic pool" of nitrogenous compounds. The Components of the general metabolic pool are used both for the synthesis of tissue constituents and for The formation of metabolic end products. In general, this proposition is undoubtedly confirmed by the experimental data obtained [73–80]; however, there are significant differences both in the relative rates of metabolism, or turnover, of individual amino acids and, in particular, in the rates of incorporation of N¹⁵-amino acids into the proteins of various Tissues. For example, Schoenheimer found that after feeding rats N¹⁵-L-leucine, Blood serum, intestinal walls, Kidneys, Spleen, Heart, Liver, and Testes take up significantly larger amounts of the isotope (per unit weight) than Hemoglobin, Muscles, and Skin. However, the largest share of the total isotope retained in the organism—about 67%—accounts for skeletal muscles.

The Mechanism of the reversible Incorporation of Amino acid residues into tissue proteins is unknown; evidently, this process is closely related to Protein Biosynthesis. Whether the dynamic state of tissues reflects the dynamic state of intracellular protein molecules has also not been definitively established. These issues are discussed below (see pp. 272, 274).

There are indications that higher plants also exhibit a dynamic state of amino acids and proteins [86], although significantly fewer studies on this issue have been conducted on plants than on rats. In studying the induced synthesis of ß-galactosidase in Escherichia coli, it was found that this enzyme is not synthesized at the expense of amino acids sourced from other cellular proteins. This process is irreversible, and according to available data, other E. coli cellular proteins do not exchange their amino acids with the amino acid "metabolic pool" used for ß-galactosidase biosynthesis (p. 275). Another example of an irreversible Protein Synthesis process is the formation of tobacco mosaic virus [87]; although the virus is synthesized from leaf protein breakdown products, no component exchange occurs between the once-synthesized virus and the leaf tissues.