Fundamentals of Biochemistry - A. A. Anisimov 1986

Integration and Regulation of Metabolism
Metabolism as a Unified System of Processes

In the preceding sections, for the sake of clarity and ease of comprehension, the METABOLISM of Proteins, Nucleic Acids, CARBOHYDRATES, Lipids, and other groups of compounds was discussed separately. However, in a living Organism, all these Metabolic pathways are interconnected; life is inconceivable without their close interplay. Furthermore, the overall metabolism of an organism should not be viewed merely as the sum of protein, carbohydrate, and other Types of Metabolism. The interaction of individual metabolic pathways gives rise to a unified system of metabolic processes—a total metabolism that represents a qualitatively new entity: life. This reflects a fundamental tenet of dialectical materialism: in complex systems, the whole is not reducible to the sum of its parts. The whole is characterized by novel qualities and properties that are absent in the individual parts (elements) yet emerge from their interaction within a specific network of relations. The interdependence of metabolic pathways across different classes of substances is particularly evident in their interconversion (although it is by no means limited to this).

12.1.1. Interconnection of Protein and Carbohydrate Metabolism. A connecting link for many metabolic pathways, including those of proteins and carbohydrates, is The Tricarboxylic Acid Cycle. The products of Glycolysis and the oxidative breakdown of carbohydrates in the TCA cycle—pyruvic, a-ketoglutaric, and oxaloacetic acids—via amination and Transamination yield numerous Amino Acids utilized for Protein Synthesis. The interaction of phosphoenolpyruvate (from glycolysis) with erythrose-4-phosphate (from the Pentose Phosphate Pathway of carbohydrate degradation) leads to the synthesis of shikimic acid, a precursor of phenylalanine, Tyrosine, and Tryptophan. Histidine is synthesized from another intermediate of The pentose phosphate cycle, ribose-5-phosphate. Thus, carbohydrate breakdown products yield amino acids through amination, which are subsequently used to synthesize proteins. It is hardly surprising, therefore, that plants under high illumination—when Photosynthesis produces abundant carbohydrates—assimilate nitrogen salts for Protein synthesis in much larger quantities than under insufficient light. This also explains the findings of D. N. Pryanishnikov (1945), who demonstrated that the carbohydrate content in plant Tissues is a crucial factor in ammonia assimilation.

The transition from proteins to carbohydrates begins with the Hydrolysis of Proteins into amino acids, which are subsequently deaminated. The resulting keto acids (Pyruvate, a-ketoglutarate, oxaloacetate) enter the TCA cycle and, via pyruvate, feed into Gluconeogenesis to form carbohydrates. However, compared to carbohydrates, proteins are far more valuable compounds for a living organism, forming the foundation of all cellular structures; consequently, their conversion into carbohydrates occurs to a limited extent in nature. In laboratory settings, however, when animals are fed a protein-rich diet, Glycogen deposition in the Liver can be observed even when carbohydrate intake is restricted or eliminated entirely. The utilization of proteins in Respiration is also exceedingly rare, occurring only under prolonged carbohydrate deprivation. Carbohydrates are actively synthesized from PROTEINS AND AMINO acids in individuals with Diabetes Mellitus. Experiments with experimentally induced diabetes in dogs have shown that 100 g of protein yields between 50 and 80 g of glucose.

Glucocorticoids, which are Hormones of the adrenal cortex, play a vital role in The conversion of amino acids into carbohydrates.

Other pathways of interaction between proteins and carbohydrates are also known. These are manifested primarily in The formation of diverse and metabolically crucial protein-carbohydrate complexes known as Glycoproteins. It should also be borne in mind that Protein Biosynthesis consumes a large amount of The energy released during carbohydrate breakdown in respiration. Conversely, every reaction in carbohydrate metabolism is catalyzed by Enzymes, all of which are proteins.

12.1.2. Interconnection of Carbohydrate and Lipid Metabolism. It is well established that excessive carbohydrate consumption (such as flour and cereal products) leads to fat accumulation in the body. Pigs, which are capable of synthesizing vast amounts of fat, are fattened using starch-rich products like potatoes and corn grain. In the bark of many trees, starch accumulated over the summer is converted into oils by late autumn. The same process occurs during the ripening of hazelnuts: in July and August, they produce a starchy "milk," which by September is replaced by a dense kernel with a high oil content.

The reverse process—the conversion of fats into carbohydrates—is clearly observed in hibernating animals (bears, marmots, hedgehogs). Over the winter, their fat reserves are almost entirely depleted, yet the level of glycogen in the liver remains sufficiently high for a long period. The conversion of fats to carbohydrates is accompanied by an increased oxygen consumption, since fats are oxygen-poor, whereas carbohydrates are significantly richer in oxygen. In plants, the active conversion of oils into carbohydrates occurs during the germination of oilseeds. The connecting link in the conversion of carbohydrates into lipids (and vice versa in Bacteria and plants) is acetyl-CoA. It is formed from pyruvic acid—the end product of carbohydrate glycolysis—and serves as the Starting Material for the synthesis of Higher Fatty acids, sterols, and polyisoprenoids. Glycerol, which is essential for the formation of many lipids, is produced by the reduction of carbohydrate glycolysis intermediates—glyceraldehyde-3-phosphate and dihydroxyacetone phosphate—followed by the Cleavage of H₃PO₄.

Conversely, glycerol, one of the primary breakdown products of lipids, is readily utilized in carbohydrate synthesis via the Formation of glyceraldehyde-3-phosphate and its entry into gluconeogenesis. In plants and microorganisms, another important lipid degradation product, acetyl-CoA, is likewise readily utilized for carbohydrate synthesis (via The Glyoxylate cycle, see Section 6.9.6).

The utilization of acetyl-CoA in animal tissues presents a more complex picture. If animals are fed carbon-labeled acetic acid, the label is incorporated into liver glycogen. However, true Synthesis of glucose from the acetyl group does not occur in the tissues of higher animals: they lack a direct metabolic pathway for utilizing acetyl-CoA in gluconeogenesis (citric acid, formed by the Condensation of acetyl-CoA with oxaloacetate, ultimately loses three carbon atoms as CO₂). Apparently, the incorporation of acetyl-CoA into carbohydrate biosynthesis in animals is indirect in nature.

12.1.3. Interconnection of Protein and Lipid Metabolism. The interactions of "proteins ⇄ carbohydrates" and "carbohydrates ⇄ lipids" just discussed provide a rationale for combining them into a single chain: "proteins ⇄ carbohydrates ⇄ lipids," in which carbohydrates act as the bridge between proteins and lipids. While this can indeed occur in nature, shorter pathways of interaction between proteins and lipids also exist. Acetyl-CoA, one of the primary breakdown products of lipids, enters the TCA cycle to form keto acids, the amination of which yields amino acids.

Another important product of lipid hydrolysis, glycerol, participates in The biosynthesis of cyclic amino acids through a long chain of conversions involving glyceraldehyde-3-phosphate and shikimic acid. To a certain extent, the reverse process—lipid synthesis at the expense of degraded proteins—is also possible. Products of AMINO ACID DEAMINATION form pyruvate via the TCA cycle and other metabolic pathways; The oxidative decarboxylation of pyruvate yields acetyl-CoA, the precursor for the synthesis of Fatty Acids and other lipid components.

Furthermore, the interdependence of proteins and lipids is directly manifested in the formation of various lipoprotein complexes. Protein Biosynthesis and function (for example, as enzymes) are invariably intertwined with the Structure and properties of Cell membranes, in which lipids play a critical role. Conversely, proteins are of paramount importance in lipid metabolism, just as they are for any other Class of compounds.

12.1.4. Unity of Metabolic Processes and the External Environment. The examination of individual metabolic interconnections clearly demonstrates The Central Role of the tricarboxylic acid cycle as the primary amphibolic pathway (see Fig. 1.1). Catabolic products resulting from The breakdown of various classes of substances enter this cycle and provide precursor molecules for the biosynthesis of numerous compounds. In many cases, the most critical junctures in this network are acetyl-CoA and pyruvate. The two-carbon fragments of acetyl-CoA act as universal building blocks into which many substances of the animal organism are "dismantled" and from which the organism can re-synthesize Other Compounds.

It is crucial to emphasize that The Unity of metabolic processes is subject to the constant Influence of Environmental conditions. This influence is manifested primarily through the continuous exchange of matter between the organism and its environment, which is a fundamental prerequisite for Life as a mode of existence of protein bodies. Enzymes, which catalyze and thereby regulate nearly all metabolic reactions, are highly sensitive to various environmental factors, such as Temperature, pH, radiation, and salt composition. Consequently, through these external conditions, enzymes exert a powerful regulatory influence on overall metabolism. The aforementioned environmental factors can also directly affect the Spatial Structure and Chemical properties of Biomolecules (especially macromolecules). Specific illustrations of environmental impacts on metabolism are provided in all preceding sections.