ENZYMES, organic substances of a protein nature that are synthesized in cells and many times accelerate the reactions occurring in them without undergoing chemical transformations. Substances that have a similar effect also exist in inanimate nature and are called catalysts.

Enzymes (from the Latin fermentum - fermentation, leaven) are sometimes called enzymes (from the Greek en - inside, zyme - leaven). All living cells contain very big set enzymes, the catalytic activity of which determines the functioning of cells. Almost each of the many different reactions occurring in a cell requires the participation of a specific enzyme. Studying chemical properties Enzymes and the reactions they catalyze are dealt with in a special, very important area of ​​biochemistry - enzymology.

Many enzymes are in a free state in the cell, simply dissolved in the cytoplasm; others are associated with complex, highly organized structures. There are also enzymes that are normally located outside the cell; Thus, enzymes that catalyze the breakdown of starch and proteins are secreted by the pancreas into the intestine. Secreted by enzymes and many microorganisms.

Action of enzymes

Enzymes involved in fundamental energy conversion processes, such as the breakdown of sugars and the formation and hydrolysis of the high-energy compound adenosine triphosphate (ATP), are present in all types of cells - animal, plant, bacterial. However, there are enzymes that are produced only in the tissues of certain organisms.

Thus, enzymes involved in cellulose synthesis are found in plant cells, but not in animal cells. Thus, it is important to distinguish between “universal” enzymes and enzymes specific to certain cell types. Generally speaking, the more specialized a cell is, the more likely it is that it will synthesize the set of enzymes needed to perform a particular cellular function.

The peculiarity of enzymes is that they are highly specific, i.e. they can accelerate only one reaction or reactions of one type.

In 1890, E. G. Fischer proposed that this specificity is due to the special shape of the enzyme molecule, which exactly matches the shape of the substrate molecule. This hypothesis is called the “key and lock”, where the key is compared to the substrate, and the lock is compared to the enzyme. The hypothesis says: the substrate fits the enzyme like a key fits a lock. The selectivity of the enzyme's action is related to the structure of its active center.

Enzyme activity

First of all, temperature affects enzyme activity. As temperature increases, the rate of a chemical reaction increases. The speed of molecules increases, they have more chances to collide with each other. Therefore, the likelihood that a reaction between them will occur increases. The temperature that ensures the greatest enzyme activity is optimal.

Beyond the optimal temperature, the reaction rate decreases due to protein denaturation. When the temperature decreases, the rate of the chemical reaction also decreases. The moment the temperature reaches freezing, the enzyme is inactivated, but does not denature.

Classification of enzymes

In 1961, a systematic classification of enzymes into 6 groups was proposed. But the names of enzymes turned out to be very long and difficult to pronounce, so it is now customary to name enzymes using working names. The working name consists of the name of the substrate on which the enzyme acts and the ending “ase”. For example, if the substance is lactose, that is, milk sugar, then lactase is the enzyme that converts it. If sucrose (ordinary sugar), then the enzyme that breaks it down is sucrase. Accordingly, enzymes that break down proteins are called proteinases.

Without enzymes, a person will not be viable, since the body requires protein molecules for all important metabolic processes and healthy digestion.

Enzymes in the human body have a protein structure. You can imagine them as catalysts in the human body that ensure the functioning of all metabolic processes. They stimulate numerous biochemical reactions and ensure that the body receives the necessary nutrients from food.

Mechanism of action

Enzymes break down nutritional components so that they can be used by the body. As a result, nutrients from food are introduced into the body.

Enzymes are actually very smart! Each of the estimated 10,000 various types Enzymes in the body have their own function: they act on a specific substrate. Thus, protein-digesting enzymes exclusively digest proteins and do not dissolve fat.

To change its function, an enzyme can briefly combine with another substrate, resulting in an enzyme-substrate complex. Subsequently, it returns to the original structure.

Main groups of enzymes in the body

Enzymes are divided into three categories: digestive, nutritional and metabolic enzymes. While digestive and metabolic enzymes are produced by the body itself, the body receives food enzymes from human consumption of raw foods.

1. Digestive. These proteins are produced in the pancreas, stomach, small intestine and salivary glands of the mouth. There they separate food molecules into basic building blocks and thereby ensure their availability for the metabolic process.

A particularly important organ for the production of many digestive enzymes is the pancreas. It produces amylase, which converts carbohydrates into simple sugars, lipase, which creates glycerol and simple fatty acids from fats, and protease, which forms amino acids from proteins.

2. Food. This group of enzymes is found in raw, fresh foods. Food enzymes act as digestive enzymes. Benefit: They directly help in digestion of food.

With the consumption of fresh fruits and raw vegetables, up to 70% of food is digested by food enzymes in the body. High temperatures destroy them, so it is important to eat the food raw. It should be as varied as possible to ensure the supply of different enzymes.

Bananas, pineapples, figs, pears, papaya and kiwi are especially rich in them. Among the vegetables, broccoli, tomatoes, cucumbers and zucchini stand out.

3. Metabolic. This group of enzymes is produced in cells, organs, bones and blood. It is only because of their presence that the heart, kidneys and lungs can function. Metabolic enzymes ensure that nutrients are efficiently absorbed from food.

Thus, they deliver vitamins, minerals, phytonutrients and hormones to the body.

Effect on skin

Hardworking biocatalyst enzymes in the body help not only inside the body, but also outside. People who suffer from acne or have sensitive skin can benefit from their appearance. To speed up the process, special enzyme peels are used. They usually consist of fruit enzymes.

Such procedures remove dead skin cells and remove excess sebum. Enzyme peels are freely sold and are very gentle on the skin. However, they should not be used more than once a week.

Key enzymes in the body

At the heart of the life activity of the human body are thousands of processes occurring in the cells. chemical reactions. Each of them is carried out with the participation of special accelerators - biocatalysts, or enzymes.

Enzymes act as catalysts in almost all biochemical reactions occurring in living organisms. By 2013, more than 5,000 different enzymes had been described

Modern science knows about two thousand biocatalysts. Let's focus on the so-called key enzymes . These include the most essential biocatalysts for the life of the body, the “breakage” of which, as a rule, leads to the occurrence of diseases. We strive to answer the question: how does this enzyme act in a healthy body and what happens to it in the process of human disease?

It is known that the most important biopolymers that form the basis of all living things (all the components of the cells of our body and all enzymes are built from them) are of a protein nature. In turn, proteins consist of simple nitrogenous compounds - amino acids, interconnected by chemical bonds - peptide bonds. There are special enzymes in the body that break down these bonds by adding water molecules (hydrolysis reaction). Such enzymes are called peptide hydrolases. Under their influence, chemical bonds between amino acids in protein molecules are broken and fragments of protein molecules are formed - peptides, consisting of various numbers amino acids. Peptides, having high biological activity, can even cause poisoning of the body. Ultimately, when exposed to peptide hydrolases, peptides either lose or significantly reduce their biological activity.

Professor V.N. Orekhovich in 1979 and his students managed to discover, isolate in pure form and study in detail the physical, chemical and catalytic properties of one of the peptide hydrolases, previously unknown to biochemists. Now it is included in the international list under the name carboxycathepsin enzyme. Research has brought us closer to the answer to the question: why does a healthy body need carboxycathepsin and what can happen as a result of certain changes in its structure.

It turned out that carboxycathepsin is involved both in the formation of the angiotensin B peptide, which increases blood pressure, and in the destruction of another peptide, bradykinin, which, on the contrary, has the property of lowering blood pressure.

Thus, carboxycathepsin turned out to be a key catalyst involved in the functioning of one of the most important biochemical systems of the body - the blood pressure regulation system. The more active carboxycathepsin is, the higher the concentration of angiotensin P and the lower the concentration of bradykinin, and this, in turn, leads to an increase in blood pressure. It is not surprising that in people suffering from hypertension, the activity of carboxycathepsin in the blood is increased. Determining this indicator helps doctors assess the effectiveness of treatment measures and predict the course of the disease.

Is it possible to inhibit the action of carboxycathepsin directly in the human body and thereby achieve a decrease in blood pressure? Research conducted at our institute has shown that in nature there are peptides that are able to bind to carboxycathepsin without undergoing hydrolysis, thereby depriving it of the ability to perform its inherent function.

Currently, work is underway on the synthesis of artificial blockers (inhibitors) of carboxycathepsin, which are supposed to be used as new therapeutic agents to combat hypertension.

Other important key enzymes involved in the biochemical transformations of nitrogenous substances in the human body include amine oxidases. The oxidation reactions of so-called biogenic amines, which include many chemical transmitters of nerve impulses - neurotransmitters, cannot occur without them. Breakdowns of amine oxidases lead to disorders of the functions of the central and peripheral nervous system; Chemical blockers of amine oxidases are already used in clinical practice as therapeutic agents, for example, for depressive conditions.

In the process of studying the biological functions of amine oxidases, it was possible to discover their previously unknown property. It turned out that certain chemical changes in the molecules of these enzymes are accompanied by qualitative changes in their catalytic properties. Thus, monoamine oxidases that oxidize biogenic monoamines (for example, the well-known neurotransmitters norepinephrine, serotonin and dopamine) partially lose their inherent properties after treatment with oxidizing agents. But they discover a qualitatively new ability to destroy diamines, some amino acids and amino sugars, nucleotides and other nitrogenous compounds necessary for cell life. Moreover, it is possible to transform monoamine oxidases not only in vitro (that is, in cases where researchers experiment with purified enzyme preparations), but also in the body of an animal, in which various pathological processes are previously simulated.

In the cells of the human body, monoamine oxidases are included in biological membranes - semi-permeable partitions that serve as cell membranes and divide each of them into separate compartments where certain reactions take place. Biomembranes are especially rich in easily oxidized fats, which are in a semi-liquid state. Many diseases are accompanied by the accumulation of excess amounts of fat oxidation products in biomembranes. Excessively oxidized (overoxidized), they disrupt both the normal permeability of membranes and the normal functioning of the enzymes that make up them. These enzymes include monoamine oxidases.

In particular, during radiation injury, fats are overoxidized in the biomembranes of cells of the bone marrow, intestines, liver and other organs, and monoamine oxidases not only partially lose their beneficial activity, but also acquire a qualitatively new property that is harmful to the body. They begin to destroy nitrogenous substances vital for the cell. The property of mono-amine oxidases to transform their biological activity is manifested both in experiments with purified enzyme preparations and in a living organism. Moreover, it turned out that the therapeutic agents used in the fight against radiation injuries also prevent the development of qualitative changes in enzymes.

This very important property - the reversibility of the transformation of monoamine oxidases - was established in experiments during which researchers learned not only to prevent the transformation of enzymes, but also to eliminate disorders, returning the functions of catalysts to normal and achieving a certain therapeutic effect.

For now we are talking about experiments on animals. However, today there is every reason to believe that the activity of amine oxidases also changes in the human body, in particular with atherosclerosis. Therefore, studying the properties of amine oxidases, as well as chemical substances, with the help of which it is possible to influence their activity in the human body with medicinal purposes, is currently continuing with particular persistence.

And one last example. It is well known what an important role carbohydrates play in the life of our body, and therefore key enzymes that accelerate their biochemical transformations. These catalysts include the enzyme gamma-amylase, discovered at our institute; it takes part in the breakdown of chemical bonds between glucose molecules (complex glycogen molecules are built from them). Congenital absence or deficiency of gamma-amylase leads to disruption of the normal biochemical transformations of glycogen. Its content in the cells of the child’s vital organs increases, they lose the ability to perform their inherent functions. All these changes characterize a severe disease - glycogenosis.

Other enzymes also participate in the biochemical transformations of glycogen.

Their congenital deficiency also leads to glycogenosis. In order to promptly and accurately recognize what type of glycogenosis a child suffers from (and this is important for choosing a treatment method and predicting the course of the disease), studies of the activity of a number of enzymes, including gamma-amylase, are necessary. Methods for differential laboratory chemical diagnosis of glycogenosis, developed at the Institute of Biological and Medical Chemistry of the USSR Academy of Medical Sciences in the 1970s, are still used in clinical practice.

According to Professor V.Z. GORKINA

Enzymes, or enzymes(from lat. Fermentum- starter) - usually protein molecules or RNA molecules (ribozymes) or their complexes that accelerate (catalyze) chemical reactions in living systems. The reactants in a reaction catalyzed by enzymes are called substrates, and the resulting substances are called products. Enzymes are substrate specific (ATPase catalyzes the breakdown of only ATP, and phosphorylase kinase phosphorylates only phosphorylase).

Enzyme activity can be regulated by activators and inhibitors (activators increase, inhibitors decrease).

Protein enzymes are synthesized in ribosomes, and RNA is synthesized in the nucleus.

The terms “enzyme” and “enzyme” have long been used as synonyms (the first mainly in Russian and German scientific literature, the second in English and French).

The science of enzymes is called enzymology, and not enzymology (so as not to mix the roots of words in Latin and Greek).

History of the study

Term enzyme proposed in the 17th century by the chemist van Helmont when discussing the mechanisms of digestion.

In con. XVIII - early XIX centuries It was already known that meat is digested by gastric juice, and astarch is converted into sugar under the influence of saliva. However, the mechanism of these phenomena was unknown.

In the 19th century Louis Pasteur, studying the conversion of carbohydrates into ethyl alcohol under the action of yeast, came to the conclusion that this process (fermentation) is catalyzed by a certain vital force located in yeast cells.

More than a hundred years ago terms enzyme And enzyme reflected different points of view in the theoretical dispute L. Pasteras on the one hand, and M. BertloiY. Liebig - on the other hand, about the nature of alcoholic fermentation. Actually enzymes(from lat. fermentum- sourdough) were called “organized enzymes” (that is, living microorganisms themselves), and the term enzyme(from Greek ἐν- - in- and ζύμη - yeast, leaven) proposed in 1876 by V. Kuehne for “unorganized enzymes” secreted by cells, for example, into the stomach (pepsin) or intestines (trypsin, amylase). Two years after the death of L. Pasteur in 1897, E. Buchner published the work “Alcoholic Fermentation without Yeast Cells,” in which he experimentally showed that cell-free yeast juice carries out alcoholic fermentation in the same way as undestroyed yeast cells. In 1907, he was awarded the Nobel Prize for this work. The first highly purified crystalline enzyme (urease) was isolated in 1926 by J. Sumner. Over the next 10 years, several more enzymes were isolated, and the protein nature of the enzymes was finally proven.

RNA catalytic activity was first discovered in the 1980s in pre-rRNA by Thomas Check, who studied ciliate RNA splicing. Tetrahymena thermophila. The ribozyme turned out to be a section of the Tetrahymena pre-rRNA molecule encoded by the intron of the extrachromosomal rDNA gene; this region performed autosplicing, that is, it cut itself out during rRNA maturation.

Functions of enzymes

Enzymes are present in all living cells and help convert some substances (substrates) into others (products). Enzymes act as catalysts in almost all biochemical reactions occurring in living organisms. By 2013, more than 5,000 different enzymes had been described. They play a vital role in all life processes, directing and regulating the body’s metabolism.

Like all catalysts, enzymes accelerate both forward and reverse reactions, lowering the activation energy of the process. The chemical equilibrium does not shift either in the forward or in the reverse direction. A distinctive feature of enzymes compared to non-protein catalysts is their high specificity—the binding constant of some substrates to protein can reach 10–10 mol/l or less. Each enzyme molecule is capable of performing from several thousand to several million “operations” per second.

For example, one molecule of the enzyme renin, contained in the gastric mucosa of a calf, curdles about 10 6 molecules of milk caseinogen in 10 minutes at a temperature of 37 °C.

Moreover, the efficiency of enzymes is much higher than the efficiency of non-protein catalysts - enzymes speed up reactions by millions and billions of times, non-protein catalysts - by hundreds and thousands of times. See also Catalytically perfect enzyme

Classification of enzymes

Based on the type of reactions they catalyze, enzymes are divided into 6 classes according to the hierarchical classification of enzymes. The classification was proposed by the International Union of Biochemistry and Molecular Biology. Each class contains subclasses, so that the enzyme is described by a set of four numbers separated by dots. For example, pepsi has the name EC 3.4.23.1. The first number roughly describes the mechanism of the reaction catalyzed by the enzyme:

CF 1: Oxidoreductases, catalyzing oxidation or reduction. Example: catalase, alcohol dehydrogenase.

CF 2: Transferases, catalyzing the transfer of chemical groups from one substrate molecule to another. Among transferases, kinases that transfer a phosphate group, usually from an ATP molecule, are especially distinguished.

CF 3: Hydrolases, catalyzing hydrolyschemical bonds. Example: esterases, pepsin, trypsin, amylase, lipoprotein lipase.

CF 4: Lyases, catalyzing the breaking of chemical bonds without hydrolysis with the formation of a double bond in one of the products.

CF 5: Isomerases, catalyzing structural or geometric changes in the substrate molecule.

CF 6: Ligases, catalyzing the formation of chemical bonds between substrates due to ATP hydrolysis. Example: DNA polymerase.

Oxyreductases- these are enzymes that catalyze oxidation and reduction reactions, i.e. transfer of electrons from donor to acceptor. Oxidation is the removal of hydrogen atoms from the substrate, and reduction is the addition of hydrogen atoms to the acceptor.

Oxidoreductases include: dehydrases, oxidases, oxygenases, hydroxylases, peroxidases, catalases. For example, the enzyme alcohol dehydrogenase catalyzes the reaction converting alcohol into aldehyde.

Oxidoreductases that transfer a hydrogen atom or electrons directly to oxygen atoms are called aerobic dehydrogenases (oxidases), while oxidoreductases that transfer a hydrogen atom or electrons from one component of the respiratory chain of enzymes to another are called anaerobic dehydrogenases. A common variant of the redox process in cells is the oxidation of hydrogen atoms of the substrate with the participation of oxyreductases. Oxidoreductases are two-component enzymes in which the same coenzyme can bind to different apoenzymes. For example, many oxidoreductases contain NAD and NADP as coenzymes. At the end of the numerous class of oxireductases (at position 11) there are enzymes such as catalases and peroxidases. Of the total number of proteins in cell peroxisomes, up to 40 percent are catalase. Catalase and peroxidase break down hydrogen peroxide in the following reactions: H2O2 + H2O2 = O2 + 2H2O H2O2 + HO – R – OH = O=R=O + 2H2O From these equations, both the analogy and significant difference between these reactions and enzymes. In this sense, catalase cleavage of hydrogen peroxide is a special case of a peroxidase reaction, where hydrogen peroxide serves as both a substrate and an acceptor in the first reaction.

Transferases- a separate class of enzymes that catalyze the transfer of functional groups and molecular residues from one molecule to another. Widely distributed in plant and animal organisms, they participate in the transformation of carbohydrates, lipids, nucleic acids and amino acids.

Reactions catalyzed by transferases generally look like this:

A-X + B ↔ A + B-X.

Molecule A here acts as a donor of a group of atoms ( X), and the molecule B is an acceptor of the group. Often one of the coenzymes acts as a donor in such transfer reactions. Many of the reactions catalyzed by transferases are reversible. Systematic names of class enzymes are formed according to the following scheme:

"donor:acceptor + group + transferase».

Or slightly more general names are used, when the name of the enzyme includes the name of either the donor or acceptor of the group:

"donor + group + transferase" or "acceptor + group + transferase».

For example, aspartate aminotransferase catalyzes the transfer of the amine group from the glutamic acid molecule, catechol-O-methyltransferase transfers the methyl group of S-adenosylmethionine to the benzene ring of various catecholamines, and ahistone acetyltransferase transfers the acetyl group from acetyl-coenzyme A to histone in the process of transcription activation.

In addition, enzymes of subgroup 7 of transferases that transfer a phosphoric acid residue using ATP as a donor of the phosphate group are often also called kinases; aminotransferases (subgroup 6) are often called transaminases

Hydrolases(KF3) are a class of enzymes that catalyze hydrolytic covalent bonds. General form The reaction catalyzed by hydrolase is as follows:

A–B + H 2 O → A–OH + B–H

The systematic name of hydrolases includes name of fissilesubstrate followed by adding -hydrolase. However, as a rule, in a trivial name the word hydrolase is omitted and only the suffix “-aza” remains.

The most important representatives

Esterases: nuclease, phosphodiesterase, lipase, phosphatase;

Glycosidases: amylase, lysozyme, etc.;

Proteases: trypsin, chymotrypsin, elastase, thrombin, renin, etc.;

Being catalysts, enzymes accelerate both forward and reverse reactions, therefore, for example, lyases are able to catalyze the reverse reaction - addition at double bonds.

Lyases- a separate class of enzymes that catalyze reactions of non-hydrolytic and non-oxidative cleavage of various chemical bonds ( C-C, C-O, C-N, C-S and others) of the substrate, reversible reactions of formation and cleavage of double bonds, accompanied by the elimination or addition of groups of atoms at its place, as well as the formation of cyclic structures.

In general, the names of enzymes are formed according to the scheme “ substrate+ lyase.” However, more often the name takes into account the subclass of the enzyme. Lyases differ from other enzymes in that catalyzed reactions involve two substrates in one direction, but only one in the reverse reaction. The name of the enzyme contains the words “decarboxylase” and “aldolase” or “lyase” (pyruvate decarboxylase, oxalate decarboxylase, oxaloacetate decarboxylase, threonine aldolase, phenylserine aldolase, isocitrate lyase, alanine lyase, ATP citrate lyase etc.), and for enzymes that catalyze reactions of water abstraction from the substrate - “dehydratase” (carbonate dehydratase, citrate dehydratase, serine dehydratase, etc.). In cases where only the reverse reaction is detected, or this direction in the reactions is more significant, the name of the enzymes contains the word “synthase” (malate synthase, 2-isopropylmalate synthase, citrate synthase, hydroxymethylglutaryl-CoA synthase, etc.) .

Examples: histidine decarboxylase, fumarate hydratase.

Isomerases- enzymes that catalyze structural transformations of isomers (racemization or epimerization). Isomerases catalyze reactions similar to the following: A → B, where B is an isomer of A.

The name of the enzyme contains the word " racemase" (alanine racemase, methionine racemase, hydroxyproline racemase, lactate racemase, etc.), " epimerase" (aldose-1-epimerase, ribulose phosphate-4-epimerase, UDP-glucuronate-4-epimerase, etc.), " isomerase" (ribose phosphate isomerase, xylose isomerase, glucosamine phosphate isomerase, enoyl-CoA isomerase, etc.), " mutase"(phosphoglycerate mutase, methylaspartate mutase, phosphoglucomutase, etc.).

Ligaza(lat. ligāre- cross-link, connect) - an enzyme that catalyzes the joining of two molecules to form a new one chemical bond (ligation). In this case, the elimination (hydrolysis) of a small chemical group from one of the molecules usually occurs.

Ligases belong to the EC 6 enzyme class.

In molecular biology, subclass 6.5 ligases are classified into RNA ligases and DNA ligases.

DNA ligases

DNA ligase performing DNA repair

DNA ligases- enzymes (EC 6.5.1.1) that catalyze the covalent cross-linking of DNA strands in a duplex during replication, repair and recombination. They form phosphodiester bridges between the 5"-phosphoryl and 3"-hydroxyl groups of neighboring deoxynucleotides at DNA breaks or between two DNA molecules. To form these bridges, ligases use the energy of the hydrolysis of the pyrophosphoryl bond of ATP. One of the most common commercially available enzymes is bacteriophage T4 DNA ligase.

Mammalian DNA ligases

In mammals, three main types of DNA ligases are classified.

DNA ligase I ligates Okazaki fragments during replication of the lagging DNA strand and is involved in excision repair.

DNA ligase III, in complex with the XRCC1 protein, is involved in excision repair and recombination.

DNA ligase IV, in complex with XRCC4, catalyzes the final step of non-homologous end joining (NHEJ) of DNA double-strand breaks. Also required for V(D)J recombination of immunoglobulin genes.

Previously, another type of ligase was isolated - DNA ligase II, which was later recognized as an artifact of protein isolation, namely the proteolysis product of DNA ligase III.

Enzyme naming conventions

Enzymes are usually named by the type of reaction they catalyze, adding the suffix -aza to the name of the substrate( For example, lactase is an enzyme involved in the conversion of lactose). Thus, different enzymes performing the same function will have the same name. Such enzymes are distinguished by other properties, for example, by optimal pH (alkaline phosphatase) or localization in the cell (membrane ATPase).

Structure and mechanism of action of enzymes

The activity of enzymes is determined by their three-dimensional structure.

Like all proteins, enzymes are synthesized as a linear chain of amino acids that folds in a specific way. Each sequence of amino acids folds in a special way, and the resulting molecule (protein globule) has unique properties. Several protein chains can be combined to form a protein complex. The tertiary structure of proteins is destroyed when heated or exposed to certain chemicals.

Active site of enzymes

The study of the mechanism of a chemical reaction catalyzed by an enzyme, along with the determination of intermediate and final products at different stages of the reaction, implies precise knowledge of the geometry of the tertiary structure of the enzyme, the nature of the functional groups of its molecule, ensuring specificity of action and high catalytic activity on a given substrate, as well as chemical nature section(s) of an enzyme molecule that provides a high rate of catalytic reaction. Typically, the substrate molecules involved in enzymatic reactions are relatively small in size compared to enzyme molecules. Thus, during the formation of enzyme-substrate complexes, only limited fragments of the amino acid sequence of the polypeptide chain enter into direct chemical interaction - the “active center” - a unique combination of amino acid residues in the enzyme molecule, ensuring direct interaction with the substrate molecule and direct participation in the act of catalysis.

The active center is conventionally divided into:

catalytic center - directly chemically interacting with the substrate;

binding center (contact or “anchor” site) - providing specific affinity for the substrate and the formation of the enzyme-substrate complex.

To catalyze a reaction, an enzyme must bind to one or more substrates. The protein chain of the enzyme folds in such a way that a gap, or depression, is formed on the surface of the globule where substrates bind. This region is called the substrate binding site. It usually coincides with or is close to the active site of the enzyme. Some enzymes also contain binding sites for cofactors or metal ions.

The enzyme combines with the substrate:

cleans the substrate from water “coat”

arranges reacting substrate molecules in space in the manner necessary for the reaction to occur

prepares substrate molecules for reaction (for example, polarizes).

Usually, the enzyme attaches to the substrate through ionic or hydrogen bonds, rarely through covalent bonds. At the end of the reaction, its product (or products) are separated from the enzyme.

As a result, the enzyme reduces the activation energy of the reaction. This happens because in the presence of the enzyme the reaction follows a different path (actually a different reaction occurs), for example:

In the absence of an enzyme:

In the presence of an enzyme:

• AF+B = AVF

  AVF = AB+F

where A, B are substrates, AB is the reaction product, F is the enzyme.

Enzymes cannot independently provide energy for endergonic reactions (which require energy to occur). Therefore, enzymes that carry out such reactions couple them with exergonic reactions that release more energy. For example, biopolymer synthesis reactions are often coupled with ATP hydrolysis reactions.

The active centers of some enzymes are characterized by the phenomenon of cooperativity.

Specificity

Enzymes generally exhibit high specificity for their substrates (substrate specificity). This is achieved by partial complementarity between the shape, charge distribution and hydrophobic regions on the substrate molecule and the substrate binding site on the enzyme. Enzymes also typically exhibit high levels of stereospecificity (forming only one of the possible stereoisomers as a product or using only one stereoisomer as a substrate), regioselectivity (forming or breaking a chemical bond at only one of the possible positions of the substrate), and chemoselectivity (catalyzing only one chemical reaction from several possible for given conditions). Despite the overall high level of specificity, the degree of substrate and reaction specificity of enzymes may vary. For example, endopeptidase trypsin only breaks the peptide bond after arginine or lysine if they are not followed by a proline, is much less specific and can break the peptide bond following many amino acids.

In 1890, Emil Fischer proposed that the specificity of enzymes is determined by the exact match between the form of the enzyme and the substrate. This assumption is called the key-lock model. The enzyme combines with the substrate to form a short-lived enzyme-substrate complex. However, although this model explains the high specificity of enzymes, it does not explain the phenomenon of transition state stabilization that is observed in practice.

Induced correspondence model

In 1958, Daniel Koshland proposed a modification of the key-lock model. Enzymes are generally not rigid, but flexible molecules. The active site of an enzyme can change conformation after binding a substrate. The amino acid side groups of the active site assume a position that allows the enzyme to perform its catalytic function. In some cases, the substrate molecule also changes conformation after binding at the active site. Unlike the key-lock model, the induced-fit model explains not only the specificity of enzymes, but also the stabilization of the transition state. This model is called the “glove hand”.

Modifications

Many enzymes undergo modifications after the synthesis of the protein chain, without which the enzyme does not fully exhibit its activity. Such modifications are called post-translational modifications (processing). One of the most common types of modification is the addition of chemical groups to side residues of the polypeptide chain. For example, the addition of a phosphoric acid residue is called phosphorylation and is catalyzed by the enzyme kinase. Many eukaryotic enzymes are glycosylated, that is, modified by oligomers of carbohydrate nature.

Another common type of post-translational modification is cleavage of the polypeptide chain. For example, chymotrypsin (a protease involved in digestion) is obtained by cleaving a polypeptide region from chymotrypsinogen. Chymotrypsinogen is an inactive precursor of chymotrypsin and is synthesized in the pancreas. The inactive form is transported to the stomach, where it is converted into chymotrypsin. This mechanism is necessary in order to avoid the splitting of the pancreas and other tissues before the enzyme enters the stomach. The inactive enzyme precursor is also called a "zymogen".

Enzyme cofactors

Some enzymes perform the catalytic function on their own, without any additional components. However, there are enzymes that require non-protein components to carry out catalysis. Cofactors can be either inorganic molecules (metal ions, iron-sulfur clusters, etc.) or organic (for example, flavinyl hem). Organic cofactors tightly bound to the enzyme are also called prosthetic groups. Organic cofactors that can be separated from the enzyme are called coenzymes.

An enzyme that requires the presence of a cofactor for catalytic activity, but is not bound to it, is called an apo enzyme. An apo enzyme in combination with a cofactor is called a holo enzyme. Most cofactors are bound to the enzyme by noncovalent but rather strong interactions. There are also prosthetic groups that are covalently bound to the enzyme, for example, thiamine pyrophosphate in pyruvate dehydrogenase.

Regulation of enzymes

Some enzymes have small molecule binding sites and may be substrates or products of the metabolic pathway in which the enzyme enters. They decrease or increase the activity of the enzyme, which creates the opportunity for feedback.

Inhibition by end product

Metabolic pathway is a chain of sequential enzymatic reactions. Often the end product of a metabolic pathway is an inhibitor of an enzyme that accelerates the first reaction in that metabolic pathway. If there is too much of the final product, then it acts as an inhibitor for the very first enzyme, and if after this there is too little of the final product, then the first enzyme is activated again. Thus, inhibition by the final product according to the principle of negative feedback is an important way of maintaining homeostasis (relative constancy of the internal environmental conditions of the body).

Influence of environmental conditions on enzyme activity

The activity of enzymes depends on the conditions in the cell or body - pressure, acidity of the environment, temperature, concentration of dissolved salts (ionic strength of the solution), etc.

Multiple Forms of Enzymes

The multiple forms of enzymes can be divided into two categories:

Isoenzymes

Proper plural forms (true)

Isoenzymes- these are enzymes, the synthesis of which is encoded by different genes, they have different primary structures and different properties, but they catalyze the same reaction. Types of isoenzymes:

Organ - glycolysis enzymes in the liver and muscles.

Cellular - malate dehydrogenase cytoplasmic and mitochondrial (the enzymes are different, but they catalyze the same reaction).

Hybrid - enzymes with a quaternary structure, formed as a result of non-covalent binding of individual subunits (lactate dehydrogenase - 4 subunits of 2 types).

Mutant - formed as a result of a single gene mutation.

Alloenzymes are encoded by different alleles of the same gene.

Actually plural forms(true) are enzymes, the synthesis of which is encoded by the same allele of the same gene, they have the same primary structure and properties, but after synthesis on ribosomachons they undergo modifications and become different, although they catalyze the same reaction.

Isoenzymes are distinct at the genetic level and differ from the primary sequence, and true multiple forms become distinct at the post-translational level.

Medical significance

The connection between enzymes and hereditary metabolic diseases was first established by A. Garrod in the 1910s. Garrod called diseases associated with enzyme defects “inborn errors of metabolism.”

If a mutation occurs in the gene encoding a particular enzyme, the amino acid sequence of the enzyme may change. Moreover, as a result of most mutations, its catalytic activity decreases or disappears completely. If an organism receives two such mutant genes (one from each parent), the chemical reaction catalyzed by this enzyme stops occurring in the body. For example, the appearance of albinos is associated with the cessation of the production of the enzyme tyrosinase, which is responsible for one of the stages of the synthesis of the dark pigment melanin. Phenylketonuria is associated with reduced or absent activity of the enzyme phenylalanine-4-hydroxylase in the liver.

Currently, hundreds of hereditary diseases associated with enzyme defects are known. Methods have been developed for the treatment and prevention of many of these diseases.

Practical use

Enzymes are widely used in the national economy - food, textile industries, pharmacology and medicine. Most drugs affect the course of enzymatic processes in the body, starting or stopping certain reactions.

The area of ​​use of enzymes in scientific research and in medicine.

In nature, there are special protein substances that function equally successfully both in a living cell and outside it. These are enzymes. With their help, the body digests food, grows and destroys cells, thanks to them all systems of our body work effectively, and, first of all, the central nervous system. Without enzymes, there would be no yogurt, kefir, cheese, feta cheese, kvass, ready-made cereals, baby food. What these biocatalysts, which have recently become faithful assistants of biotechnologists, consist of and how they are structured, how they are distinguished from each other, how they make our lives easier, you will learn about this in this lesson.

Bibliography

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