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Biological oxidation

Biological oxidation (cellular or tissue respiration) is a redox reaction occurring in the cells of the body, as a result of which complex organic substances are oxidized with the participation of specific enzymes by oxygen delivered by the blood. The final products of biological oxidation are water and carbon dioxide . The energy liberated in the process of biological oxidation is partially released as heat, the main part of which goes to the formation of molecules of complex organophosphorus compounds (mainly adenosine triphosphate - ATP), which are sources of energy necessary for the body’s vital activity.

In this case, the oxidation process consists in taking away from the oxidized substance (substrate) electrons and the number of protons equal to them. Substrates of biological oxidation are products of transformations of fats, proteins and carbohydrates . Biological oxidation of substrates to final products is carried out by a chain of successive reactions, the number of intermediates of which include tricarboxylic acids — citric, cisaconitic, and isolimic acids; therefore, the entire chain of reactions is called the tricarboxylic acid cycle, or the Krebs cycle (after the researcher who established this cycle).

The initial reaction of the Krebs cycle is the condensation of oxalo-acetic acid with an activated form of acetic acid (acetate), which is a compound with acetylation coenzyme acetyl-CoA. As a result of the reaction, citric acid is formed, which, after four times dehydrogenation (cleavage of 2 hydrogen atoms from the molecule) and two-fold decarboxylation (cleavage of the CO2 molecule), forms oxaloacetic acid. Acetic acid , pyruvic acid - one of the products of glycolysis (see), fatty acids (see), etc. are sources of acetyl CoA used in the Krebs cycle, etc. Along with the oxidation of acetyl CoA in the Krebs cycle, oxidation and other substances can occur , able to turn into intermediate products of this cycle, for example, many of the amino acids formed during the breakdown of the protein. Due to the reversibility of most of the reactions of the Krebs cycle, the decomposition products of proteins, fats and carbohydrates (intermediates) in it can not only be oxidized, but also produced when it is reversed. This is the connection between the metabolism of fats, proteins and carbohydrates.

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The oxidation reactions occurring in the Krebs cycle are not accompanied, as a rule, by the formation of energy-rich compounds. The exception is the conversion of succinyl-CoA to succinate (see Succinic acid), which is accompanied by the formation of guanosine triphosphate. Most of the ATP is formed in the chain of respiratory enzymes (see), where the transfer of electrons (and in the first stages and protons) to oxygen is accompanied by the release of energy.

Hydrogen cleavage reactions are carried out by dehydrogenase class enzymes, with hydrogen atoms (i.e., protons + electrons) attached to coenzymes: nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide phosphate (NADP), flavadin adenine dinucleotide (FAD), etc.

The processes of biological oxidation associated with the Krebs cycle and the chain of respiratory enzymes occur predominantly in the mitochondria and are localized on their membranes.

Thus, the processes of biological oxidation associated with the Krebs cycle, are important as the formation of compounds rich in energy, and for the implementation of the connection of carbohydrate, fat and protein metabolism. Other types of biological oxidation, apparently, have a narrower meaning, such as energy supply of cells. Such is the stage of glycolysis, which consists in the oxidation of a number of phosphorus compounds with simultaneous reduction of NAD and the formation of ATP or the reaction of the pentose cycle (i.e., the oxidative conversion of glucose-6-phosphate), accompanied by the formation of phosphoentotosis and reduced NADPH. The pentose cycle plays an important role in tissues characterized by intensively proceeding syntheses - nucleic, fatty acids, cholesterol , etc. See also metabolism and energy.

Biological oxidation is a combination of redox reactions occurring in biological objects. Under the process of oxidation, we understand the loss by a substance of electrons or electrons and protons simultaneously (loss of hydrogen atoms) or the addition of oxygen. Reactions in the opposite direction characterize the recovery process. Reducing agents are electrons that lose electrons, oxidants are substances that acquire electrons. Biological oxidation is the basis of tissue, or cellular, respiration (the process by which tissues and cells absorb oxygen and release carbon dioxide and water) - the main source of energy for the body. The substance accepting (accepting) electrons, that is, recovering, is molecular oxygen, which turns into an anion of oxygen O —— . Hydrogen atoms, split off from organic matter - the substrate of oxidation (SH 2 ), are converted with the loss of electrons into protons or positively charged hydrogen cations:

As a result of the reaction between hydrogen cations and oxygen anions, water is formed, and the reaction is accompanied by the release of a significant amount of energy for every 18 g of water). Carbon dioxide is produced as a by-product of biological oxidation. Some of the reactions of biological oxidation lead to the formation of hydrogen peroxide, under the influence of catalase decomposes into H 2 O and O 2 .

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Suppliers of energy in the human body are foods - proteins, fats and carbohydrates. However, these substances cannot serve as substrates for biological oxidation. They are preliminarily digested in the digestive tract, where amino acids are formed from proteins, fatty acids and glycerin from fats, and monosaccharides from complex carbohydrates, primarily hexoses. All of these compounds are absorbed and enter (directly or through the lymphatic system) into the blood. Together with similar substances formed in organs and tissues, they constitute the “metabolic pool”, from which the body draws material for biosynthesis and for satisfying energy needs. The main substrates of biological oxidation are products of tissue metabolism of amino acids, carbohydrates and fats, which are called substances of the “citrate cycle”. These include acids:
citric, cisaconitic, isolimone, oxalo-amber, α-ketoglutaric, amber, fumaric, malic, oxaloacetic.


Pyruvic acid CH 3 —CO — COOH does not enter directly into the citric acid cycle, but plays a significant role in it, as does the product of its decarboxylation — the active form of acetic acid CH 3 SOAco (acetyl-coenzyme A).

The processes included in the "citrate cycle" ("Krebs cycle", "tricarboxylic acid cycle"), occur under the action of enzymes enclosed in cell organelles, called mitochondria. The elementary act of oxidation of any substance entering the citric acid cycle is the removal of hydrogen from this substance, i.e., an act of dehydrogenation, due to the activity of the corresponding specifically acting enzyme dehydrogenase (Fig. 1).


Fig. 1. Scheme of the Krebs citrate cycle.

If the process starts with pyruvic acid, then the removal of two hydrogen atoms (2H) in the Krebs cycle is repeated 5 times and is accompanied by three successive stages of decarboxylation. The first act, dehydrogenation, occurs when pyruvic acid is converted to acetyl CoA, which condenses with oxaloacetic acid to citric acid. The second time dehydrogenation leads to the formation of oxalo-succinic acid from isolimone. The third act - the elimination of two hydrogen atoms - is associated with the transformation of ketoglutaric acid into succinyl-CoA; the fourth - with the dehydrogenation of succinic acid; and finally, the fifth - with the transformation of malic acid into oxaloacetic acid, which can again enter into condensation with acetyl-CoA and ensure the formation of citric acid. During the decomposition of succinyl-CoA, an energy-rich bond (~ P) is formed - this is the so-called substrate phosphorylation: Succinyl-CoA + H 3 PO 4 + ADP → succinic acid + CoA + ATP.


Fig. 2. Scheme of dehydrogenation of citrate cycle substrates by specific enzymes consisting of dissociating complexes: proteins - b1, b2, b3 and b4 with NAD and NADH2 and protein b5, forming a complex with FAD (succinic dehydrogenase); CAC is cisacitic acid.

Four of these acts of dehydrogenation are carried out with the participation of specific dehydrogenases, the coenzyme of which is nicotinamide adenine dinucleotide (NAD). One act - the conversion of succinic acid to fumaric acid - occurs under the influence of succinine dehydrogenase - flavoprotein I. In this case, the coenzyme is flavin adenine dinucleotide (FAD). As a result of five repeated acts of dehydrogenation (Fig. 2), during reactions occurring in the citric acid cycle, reduced forms of coenzymes are formed: 4-NADH2 1-FADH2. The dehydrogenase of reduced NAD, i.e., accepting hydrogen with NADH2, also belongs to the flavin enzymes - this is flavoprotein II. However, it differs from succinic dehydrogenase in the structure of both the protein and the flavin component. Further oxidation of reduced forms of flavoproteins I and II containing FADH2 occurs with the participation of cytochromes (see), which are complex proteins — chromoproteins containing iron porphyrins — hemes.

When FADH2 is oxidized, the paths of the proton and electrons diverge: protons enter the environment in the form of hydrogen ions, and electrons through a series of cytochromes (Figure 3) are transferred to oxygen, turning it into an oxygen anion O —— . Between FADH2 and the cytochrome system, another factor appears to be involved — coenzyme Q. Each subsequent link in the respiratory chain from NADH2 to oxygen is characterized by a higher redox potential (see). Throughout the entire respiratory chain from NADH2 to ½O 2, the potential changes by 1.1 V (from -0.29V to + 0.81V). With full oxidation, for example, pyruvic acid, accompanied by a fivefold cleavage of hydrogen, the energy efficiency of the process will be about 275 kcal (55X5). This energy is not completely dissipated as heat; about 50% of it is accumulated in the form of energy-rich phosphorus compounds, mainly adenosine triphosphate (ATP).

The process of transformation of the energy of oxidation into energy-rich bonds (~ P) of the final phosphate residue of the ATP molecule is localized in the internal mitochondrial membranes and is associated with certain stages of the transfer of hydrogen and electrons along the respiratory chain (Fig. 4). It is believed that the first phosphorylation is associated with the transport of hydrogen from NADH2 to FAD, the second is associated with electron transfer to cytochrome c1 and, finally, the third, least studied, is located between cytochromes c and a.


Fig. 3. Diagram of the transfer of hydrogen and electrons through the respiratory chain; Е0 - redox potential.


Fig. 4. Scheme of transformation of the energy of oxidation into energy-rich bonds ~ P: KoQ - coenzyme Q; SH2 - oxidation substrate; CS1, CS, TS (A + A3) - cytochromes C1, C, (A + A3); J1, J2, J3 - specific for this link of the respiratory chain compounds involved in the formation of energy-rich bonds; X is a non-specific substance that forms energy-rich bonds with J1, J2, J3, replacing them with phosphate residues and transferring them to adenosine diphosphoric acid (ADP) to form ATP.

The mechanism of formation of energy-rich bonds has not yet been deciphered. It was found, however, that the process consists of several intermediate reactions (in Fig. 4 — from J ~ X to ATP), only the last of which is the formation of energy-rich phosphate residue ATP. The energy-rich bond of the final phosphate group in ATP is estimated at 8.5 kcal per gram molecule (about 10 kcal under physiological conditions). When transferring hydrogen and electrons along the respiratory chain, starting with NADH2 and ending with the formation of water, 55 kcal are released and accumulate in the form of ATP of at least 25.5 kcal (8.5X3). Therefore, the energy efficiency of the process of biological oxidation is about 50%.


Fig. 5. Scheme of using the energy of phosphate bonds of ATP (AMP — P ~ P) for various physiological functions.

The biological meaning of phosphorylating oxidation is clear (Fig. 5): all vital processes (muscle work, nervous activity, biosynthesis) require energy, the edge is provided by breaking energy-rich phosphate bonds (~ P). The biological meaning of non-phosphorylating-free-oxidation can be seen in numerous oxidation reactions not related to the citrate cycle and the transfer of hydrogen and electrons through the respiratory chain. These include, for example, all the extra-mitochondrial oxidation processes, the oxidative removal of toxic active substances, and many acts regulating the quantitative content of biologically active compounds (some amino acids, biogenic amines, adrenaline, histidine, serotonin, etc., aldehydes, etc.) by more or less intense oxidation. The ratio of free and phosphorylating oxidation is also one of the ways of thermoregulation in humans and warm-blooded animals. See also Metabolism and energy.