Fundamentals of Biochemistry - Filippovich, Y. B. 1999

Water and Mineral Metabolism
Mineral Metabolism

A monumental role in the Development of concepts regarding mineral METABOLISM was played by the works of K. A. Timiryazev, whose research on The Significance of zinc in plant Nutrition (1872) laid one of the foundational stones for the science of Trace Elements. This was hardly a coincidence, as modern data indicate that Zn holds the record for the number of Zn-dependent Enzymes—currently numbering around 120. The brilliant works of V. I. Vernadsky (1922) demonstrated the profound connection between the Elemental Composition of organisms and the Earth's crust, while the studies of his student, A. P. Vinogradov (1939), advanced THE CONCEPT OF biogeochemical provinces, which focuses on the delicate interdependence of elements within the soil–plant–animal system. An excess or deficiency of a particular element within a biogeochemical province leads to endemics—diseases affecting plants and animals. At The current stage of mineral metabolism research, The Link Between biological activity, atomic Structure, and consequently, an element's position in Mendeleev's periodic table is becoming increasingly evident.

The Study of The Role of mineral elements in metabolism has recently given rise to a new discipline—bioinorganic chemistry (or inorganic biochemistry), the Subject Matter of which was outlined above (see Introduction).

The involvement of Mineral Substances in The formation of the Tertiary and Quaternary structures of Biopolymers. The most fundamental mechanism by which mineral compounds participate in vital processes is their ability to bind with high-molecular-weight substances, such as Proteins and Nucleic Acids. As a result of this interaction, Metal Ions, alongside other factors, help maintain the specific spatial conformation of biopolymers, which plays a critical role in the biological activity of macromolecules. Consequently, the normal execution of enzymatic, hormonal, and other Functions by proteins, the unhindered expression of Genetic information encoded in nucleic acids, the assembly of supramolecular complexes, the formation of subcellular particles, and similar processes are inconceivable without the participation of cations and anions.

Let us examine a few Examples to illustrate the General Principles discussed above. Zn²⁺ plays an outstanding role in forming the active conformation of the Insulin hormone (see p. 451). It is possible that the lack of proper hormonal activity in synthetic insulin is due to subtle structural features that prevent the formation of a biologically active complex between protomers and Zn²⁺. Furthermore, the conformation of high-polymer RNA molecules is largely determined by the Ionic strength of the solution, while many divalent cations (Cr, Ni, Fe, Zn, Mn, etc.) take direct part in forming the helical Structure of Nucleic Acids.

A striking illustration of the involvement of cations in the assembly of supramolecular structures is the dependence of ribosome association–dissociation on the concentration of Mg²⁺ (see p. 285); the same ion stabilizes the Tertiary Structure of tRNA. The activity of the vast majority of enzymes involved in free and phosphorylation-coupled oxidation of Organic compounds is impossible without Fe and Cu ions.

The number of such examples could easily be multiplied. All of them indicate that the ESTABLISHMENT OF THE structure of biopolymers and biocomplexes is largely determined by the presence or absence of adequate quantities of specific cations and anions within the cellular contents. Therefore, it is entirely natural that mineral substances exert a profound influence on enzymatic processes, the metabolism of various compounds, morphogenetic processes, and more. Their role in the vital activity of organisms is immense.

The participation of mineral substances in Enzymatic Catalysis. More than a quarter of currently known enzymes depend on metals for their activity. In most cases, metal ions form loose bonds with the apoenzyme, creating a readily dissociable complex. As a metal-enzyme complex, the enzyme achieves maximum activity by adopting the proper spatial configuration. Thus, metal ions act here as organizers of the enzyme's tertiary structure, specifically in shaping its active sites. This is precisely how univalent metal ions interact with more than 60 enzymes, and zinc ions with over 30 enzymes of animal, plant, and bacterial origin. Certain cations also play a crucial role in forming multimeric enzymes, where linkages between individual protomers are mediated by metal ions. Such cations include Mg²⁺, Mn²⁺, Zn²⁺, Ca²⁺, and others. α-Amylase has been studied in particularly great detail in this regard: in the presence of Ca²⁺, both the tertiary and quaternary structures of this enzyme are stabilized, rendering it resistant to gastrointestinal peptidases.

Much less frequently, metal ions form stable bonds with the protein-enzyme. In such cases, the metal is not separated from the enzyme by dialysis or passage through an ion exchanger, meaning the enzyme is a true metalloprotein. Examples include the incorporation of Cu and Fe ions in iron-sulfur proteins and blue oxidases (see p. 414). To some extent, these Metalloproteins are analogous to selenoproteins, which have recently attracted considerable attention (including enzymes such as formate and xanthine dehydrogenase, thiolase, Glutathione peroxidase, etc.).

A fairly widespread mechanism of metal ion involvement in enzymatic activity is their incorporation into the enzyme's prosthetic group. Cytochromes serve as a classic example of this enzyme type.

Finally, many cations (Mg²⁺, Mn²⁺, Zn²⁺, etc.) actively participate in enzymatic catalysis by briefly forming very weak bonds with either the substrate and the enzyme (during the Formation of the enzyme-substrate complex) or the coenzyme and the apoenzyme (in two-component enzymes). Examples of the first type are numerous, representing one of the earliest concepts regarding the potential role of cations in enzymatic catalysis. The formation of a ternary enzyme-metal-substrate complex has been observed in the action of arginase, peptidases, carboxylases, and many Other Enzymes. An example of the second type is the attachment of a flavin coenzyme to the apoenzyme mediated by Fe, Mo, Cu, and Zn ions.

Table 26 presents data on the activation of certain enzymatic processes by metal cations.

Because mineral compounds are intimately linked to enzymatic reactions, they practically influence all aspects of metabolism. Let us examine specifically how the metabolism of nucleic acids, proteins, CARBOHYDRATES, and Lipids depends on the presence of particular cations and anions.

Mineral compounds and NUCLEIC ACID METABOLISM. A number of cations take direct part in maintaining the secondary and tertiary structures of DNA and RNA. Specifically, this function is attributed to Fe, Cu, Mn, Zn, Co, and Ni ions, which have been detected in highly purified DNA and RNA preparations. In the presence of certain listed cations, the melting Temperature of nucleic acids increases, indicating greater stability of their molecules. It is hypothesized that this stabilization is achieved through the formation of intermolecular cross-links via metal ions in a "sandwich"-type arrangement. Similarly, metal ions contribute to The structure of Nucleoproteins by bridging PROTEIN AND NUCLEIC acid molecules. At the same time, heavy metals (copper, mercury, cadmium, and zinc) have been found to alter key stages of genetic information expression (DNA, RNA, and Protein Synthesis) in Bacteria, Algae, and Protozoa.

Class="center">Table 26 Enzymes activated by metal cations

Almost all enzymes accelerating the breakdown and synthesis of nucleic acids, NUCLEOTIDES, nucleosides, and purine and pyrimidine bases are activated by metal ions. The role of Mg²⁺ is particularly significant: it activates DNA and RNA polymerases, polynucleotide phosphorylase, nucleotidase, RNase, DNase, and a number of other enzymes involved in nucleic acid metabolism. Ca and Ba ions increase RNase activity, whereas Zn decreases it. It has recently been established that Zn²⁺ is essential for the functioning of DNA polymerases and Reverse Transcriptase. DNA degradation by DNase is enhanced in the presence of Mn²⁺, Ca²⁺, Fe²⁺, and Co²⁺. Mn ions activate phosphodiesterases, Mo ions activate xanthine oxidase, while copper ions inhibit the latter. Se⁴⁺ selectively inhibits the Transcription of ribosomal genes; similarly, compounds of La, Pr, Nd, and Sm inhibit RNA Biosynthesis in Liver Cell nuclei.

Interesting findings have been obtained regarding the role of boron in nucleic acid metabolism. Unlike all other elements, boron does not act as a cofactor or enzyme activator. However, in its absence, the de novo synthesis of nucleic acids is severely inhibited, and their degradation is accelerated due to increased RNase activity. It is suggested that boron's effect on nucleic acid metabolism is linked to its involvement in Oxidative Phosphorylation AND the synthesis of nucleoside triphosphates—the starting compounds for nucleic acid biosynthesis. Mg²⁺ is equally important for coupling oxidation with phosphorylation, since the Mg²⁺ ∙ ADP complex participates directly in the ATP synthase reaction (see Chapter X).

Recently, growing importance has been attributed to the role of Cu and Mo ions in nucleic acid metabolism.

The role of mineral elements in Protein metabolism. The breakdown and synthesis of proteinaceous matter heavily depend on a number of mineral elements. Mn, Fe, Zn, Co, and Ni ions enhance the activity of peptidases and arginase, thereby participating in protein degradation. Protein Biosynthesis proceeds with the direct participation of K, Mg, and Mn ions. The first two are necessary to maintain Ribosomes in a functionally active state, with the concentration of Mg²⁺ determining the error rate in codon-anticodon recognition. The third ensures the peptidyl transferase reaction during polypeptide chain assembly. Ni ions influence the release of many Peptide Hormones upon the completion of their biosynthesis, while Ca ions play a central role in the functioning of contractile proteins. Mitochondrial cuproprotein, mitohondrocuperin, serves as a copper store for cytochrome c oxidase synthesis.

The question of the role of mineral elements in Amino acid metabolism has not yet been fully elucidated; nevertheless, It is worth noting the great importance of Co ions in Methionine biosynthesis, Mg and Mn in amino acid metabolism Reactions Involving the transfer of single-carbon fragments (such as the synthesis of Serine from Glycine, or citrulline from Ornithine and carbamoyl phosphate), Fe in The conversion of phenylalanine to Tyrosine, Zn in the incorporation of glycine into liver glutathione, and Se in The oxidation of -SH groups in Cysteine residues within proteins.

The involvement of mineral compounds in carbohydrate and Lipid Metabolism. Various cations take an active part in the breakdown and synthesis of both Carbohydrates and lipids directly, as well as their degradation products, which undergo final oxidation in the tricarboxylic and Dicarboxylic Acid Cycle.

The central element in Glycolysis is Mg: it activates the majority of glycolytic enzymes. In certain instances (the hexokinase reaction, the conversion of 1,3-diphosphoglyceric acid to 3-phosphoglyceric acid, and 2-phosphoglyceric acid to phosphoenolpyruvate), it can be substituted by Mn. The significance of Ca²⁺ in maintaining the structure of α-amylase was noted earlier; it is worth emphasizing that lanthanides, such as Lu³⁺, activate α-amylase just as successfully as Ca²⁺. The de novo FORMATION OF CARBOHYDRATES during Photosynthesis is impossible without the participation of magnesium (a constituent of chlorophyll), manganese (involved in photosynthetic phosphorylation), and iron (necessary for chlorophyll biosynthesis). Several other elements (Cu, Zn, Mo, Co, and B) are also vital for photosynthesis.

The breakdown of both simple and Complex Lipids is activated by Ca²⁺, as this cation positively influences the activity of lipase, phospholipases A and C, and lipoprotein lipase. The β-oxidation of acyl-CoA proceeds more vigorously in the presence of Cu and Fe ions. Mg²⁺ is required for the synthesis of acetyl-CoA, phosphocholine, and Choline phosphatides.

The final stage of aerobic carbohydrate and lipid degradation via the tricarboxylic and dicarboxylic acid cycle (Respiration) is carried out with the active participation of Mn²⁺, which activates nearly all Enzymes of the Krebs cycle. A similar effect is exerted by Mg²⁺ and, in some cases, Co²⁺ and Zn²⁺.

Mineral metabolism. Mineral substances entering plant or animal organisms that are necessary for various physiological functions are retained within the Organism, in the vast majority of cases forming specific compounds. The bioaccumulation of elements is species-specific and hereditary. For instance, over 150 plant species (such as Solanaceae and Ranunculaceae) accumulate Li, clubmosses accumulate Al, marine algae accumulate I (in the form of tyrosine derivatives) and polyvalent metals (amounting to 10⁸ tons annually), the fly agaric mushroom accumulates Se (as Se-cysteine, where Se replaces S), and so forth.

Among macroelements, Ca and P combine in higher animals to form calcium phosphate, the foundational matrix of Bone tissue. Sulfur is largely incorporated into organic compounds (such as the HS groups in Amino Acids, Peptides, and proteins, and HO₃S groups in Heteropolysaccharides). Phosphorus is likewise frequently present as organic derivatives (including sugar phosphates and Phosphoproteins). Mg, K, and Na typically exist in ionic forms, which are primarily balanced by chloride, phosphate, and carbonate anions. Furthermore, Mg and Fe are prominent Structural components of chlorophyll and Hemoglobin.

Trace elements predominantly interact with proteins and nucleic acids, either directly or by first being incorporated into organic prosthetic groups.

Although not universally applicable, minerals that are useless to the organism are generally unabsorbed. A case in point is silicic acid: when present at a 5% level in green plant fodder (calculated on a dry matter basis), it is not assimilated by animals, is excreted entirely in the feces, and serves as an inert marker for calculating feed digestibility. At the same time, evidence has emerged suggesting that silicic acid may play a role in Collagen maturation and proteoglycan formation, and that certain organosilicon compounds exert a positive effect on animal productivity.

The turnover of various mineral elements proceeds quite vigorously. This is particularly evident when an element is excreted from the body as part of a normal metabolic product. For instance, mammals excrete large quantities of Ca and P during Lactation. Yet individual elements also exchange quite intensively at THE CELLULAR LEVEL, as reflected by changes in their concentration within subcellular structures and cellular compartments, as well as their Active Transport across membranes. Mediated by a variety of bacteria, elements such as Hg, As, Te, Tl, Au, Pb, Sn, and Cd undergo methylation to yield highly toxic products (such as Hg and Pb) that are lethal to animals in nanogram quantities, although humans can tolerate a daily methylmercury dose of 0.03 mg without adverse effects.

A characteristic feature of mineral element metabolism is, on the one hand, the interchangeability of several of these elements and, on the other, their antagonistic actions. For example, in enzymatic processes where K⁺, NH₄⁺, or Rb⁺ act as activators (such as in the action of Yeast aldehyde dehydrogenase), Na⁺, Li⁺, or Cs⁺ function as inhibitors. Similar relationships exist between Mg²⁺ and Ca²⁺, Mn²⁺ and Zn²⁺, Ni²⁺ and Cu²⁺, and so forth. Conversely, Ni ions on the one hand, and Zn and Fe on the other, exhibit synergistic action.

A change in an element's valence state during metabolism is accompanied by a dramatic shift in its physiological activity. Thus, Cr³⁺ stimulates protein, carbohydrate, and LIPID METABOLISM IN humans and animals, whereas Cr⁶⁺ blocks oxidative phosphorylation in their Mitochondria.

The significance of minerals in agriculture. The extensive involvement of mineral compounds in building PLANT AND ANIMAL Tissues, maintaining the structural integrity of biopolymers, and driving diverse biochemical processes within the organism underpins their profound importance for crop production, animal husbandry, and medicine.

A prominent role in developing the Theoretical Aspects of mineral nutrition and their Practical Application in agriculture belongs to K. A. Timiryazev and his pupil N. D. Pryanishnikov. The sweeping creative program they outlined for introducing chemistry into agriculture—known as chemicalization—was vigorously implemented in our country.

Ranking second in the world in mineral fertilizer production, our chemical industry has mastered the manufacture of several new types (including nitrophoska, urea, and defluorinated phosphates). The transition to concentrated fertilizers free of ballast substances is fundamentally important. At the same time, a number of problems have arisen regarding the need to regulate fertilizer application in agricultural production (such as the nitrate and nitrite issue, soil salinization, The Use of settling sludge from irrigation fields, and eutrophication of Water bodies), as well as the technogenic contamination of the environment with mineral elements at concentrations detrimental to nature. These challenges can be addressed only through measures implemented within the framework of global environmental programs.

The resource base for producing potash and nitrogen fertilizers is virtually inexhaustible. However, phosphorite deposits will suffice for only a few decades, though it is hoped that volcanic phosphates can be discovered and utilized. As for trace elements, the modern chemical industry fully meets the demands of agricultural production. Of paramount importance is the shift toward poorly soluble, slowly hydrolyzing fertilizers that persist in the soil for extended periods (properties exhibited, for example, by the salt MgNH₄PO₄). Plans are underway to launch The production of complex fertilizers (particularly those based on urea, which has a high capacity for complexation) and intricate fertilizer blends.

In animal husbandry, farm animals are widely supplemented with compounds of Na, K, Ca, P, Cu, I, Co, Mn, Zn, and other elements. Consequently, animals utilize feed more efficiently and gain weight faster. Livestock productivity increases by an average of 10% when rations are fully balanced regarding mineral elements and other constituents. During cattle fattening, the inclusion of macroelements in the diet yields an 11–14% increase, and microelements a 12–15% increase, in live weight gain compared to control groups of animals.