Lecture 15. Enzymes: structure, properties, functions.

Lecture Plan:

1. The overall characteristics of enzymes.

2. The structure of enzymes.

3. The mechanism of enzymatic catalysis.

4. Properties of enzymes.

5. Nomenclature of enzymes.

6. Classification of enzymes.

7. Isoenms

8. Kinetics of enzymatic reactions.

9. Units for measuring enzymatic activity

1. The overall characteristics of enzymes.

In normal physiological conditions, biochemical reactions in the body flow with high speeds, which is ensured by biological protein catalysts - enzymes.

The study of enzymology is engaged in studying, the science of enzymes (enzymes), specific proteins - catalysts, synthesized by any living cell and activating various biochemical reactions occurring in the body. Some cells may contain up to 1000 different enzymes.

2. The structure of enzymes.

Enzymes are proteins with a high molecular weight. Like any proteins, enzymes have primary, secondary, tertiary and quaternary levels of organization of molecules. Primary structure It is a sequential compound of amino acids and is due to the hereditary features of the body, it is precisely it that characterizes the individual properties of enzymes. Secondary structure enzymes are organized in the form of alpha spiral. Tertiary structure It has the form of globules and participates in the formation of active and other centers. Many enzymes have quaternary structure and they are the association of several subunits, each of which is characterized by three levels of the organization of molecules of differing from each other, both in high-quality and quantitative ratios.

If enzymes are represented by simple proteins, i.e. consist only of amino acids, they are called simple enzymes. Simple enzymes include pepsin, amylase, lipase (almost all GI enzymes).

Complex enzymes consist of protein and non-discharge parts. The protein part of the enzyme is called - aPOPHERMENT, non-worker - coherent. The coenzyme with the Apuniment form holoferment. The coenzyme can be connected to the protein part or only at the time of the reaction, or to bind to each other with a constant durable connection (then the non-discovered part is called - prosttic group). In any case, non-discreet components are directly involved in chemical reactions by interacting with the substrate. The coenses can be represented:

Nucleosidtriphosphates.

Minerals (zinc, copper, magnesium).

The active forms of vitamins (B 1 is part of the enzyme - decarboxylase, in 2 - enters dehydrogenase, in 6 - enters transferase).

The main functions of the coenzymes:

Participation in the act of catalysis.

Contact between the enzyme and the substrate.

Stabilization of apopherge.

Apoperment, in turn, enhances the catalytic activity of the non-chicken part and determines the specificity of the action of enzymes.

In each enzyme there are several functional centers.

Active Center - The zone of the enzyme molecule, which specifically interacts with the substrate. The active center is represented by functional groups of several amino acid residues, it is precisely an attachment and a chemical transformation of the substrate.

Alosteric center Or regulatory is the enzyme zone responsible for the attachment of activators and inhibitors. This center is involved in the regulation of enzyme activity.

These centers are located on different sections of the enzyme molecule.

The first enzymatic reaction of the precipitation of starch malt was investigated by the domestic scientist K. MENTEN developed the theory of enzymatic catalysis. Sumner first allocated the purified drug of the urease enzyme in the crystalline state. Merrifield managed to implement the artificial synthesis of the RNA-Ase enzyme.

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abstract

Structure, properties and mechanism of enzyme action

Brief history of enzymology

Experimental study of enzymes in the 19th century coincided with the study of yeast fermentation processes, which was reflected in the terms "enzymes" and "enzymes". The name enzymes originated from the Latin word Fermentatio - fermentation. The term enzymes occurred from the concept of EN Zyme - from yeast. Initially, these names were given different meaning, but at present they are synonymous.

The first enzymatic reaction of precipitation of starch malt was investigated by domestic scientist K.S. Kirchhoff in 1814. Subsequently, attempts were made to allocate enzymes from yeast cells (E. Buchner, 1897). At the beginning of the twentieth century, L. Michaelis and M. Menten developed the theory of enzymatic catalysis. In 1926, D. Samner first allocated the purified drug enzyme urease in the crystalline state. In 1966, B. Merrifield managed to carry out artificial synthesis of the RNA-Ase enzyme.

The structure of enzymes

Enzymes are highly specialized proteins capable of raising the reaction rate in living organisms. Enzymes - biological catalysts.

All enzymes are proteins, as a rule, globular. They can relate to both simple and complex proteins. The protein part of the enzyme can consist of one polypeptide chain - monomeric proteins - enzymes (for example, pepsin). A number of enzymes are oligomeric proteins, include several protéers or subunits in their composition. Proteters, combining into an oligomeric structure, are connected by spontaneously fragile non-covalent bonds. In the process of association (cooperation), structural changes in individual protéers occur, as a result of which the activity of the enzyme increases noticeably. The separation (dissociation) of the protéer and their union into the oligomeric protein is the mechanism for regulating the activity of enzymes.

Subunits (proteers) in oligomers can be either identical or different from the primary - tertiary structure (conformation). In the case of a compound of various protéers, multiple forms of the same enzyme occur in the oligomeric structure of the enzyme -isoenms.

The isoenzymes catalyze the same reaction, but differ in the set of subunits, physico-chemical properties, electrophoretic mobility, on the affinity of substrates, activators, inhibitors. For example,lactate dehydrogenase (LDH) - Enzyme, oxidizing milk acid into pyruogradic acid, is a tetramer. It consists of four proteers of two types. One type of protéer is denoted by H (isolated from the heart muscle), the second propter is indicated by M (isolated from skeletal muscles). It is possible 5 combinations of these protéers in the composition of LDH:H 4, H 3 m, H 2 m 2, H 1 m 3, m 4.

Biological role of isfeimments.

• Isoenms ensure the flow of chemical reactions in accordance with the conditions in different organs. So, the isoenzyme LDH1 - It has a high oxygen affinity, so it is active in tissues at a high speed of oxidative reactions (red blood cells, myocardium). Ioferment LDH5 active in the presence of high lactate concentration, most characteristic of the liver tissue
• Pronounced Organshipity is used to diagnose diseases of various organs.
• Celebrations change their activity with age. So, in the fetus, with a lack of oxygen, LDH prevails3 , and with an increase in age, the increase in oxygen income increases the share of LDH2 .

If the enzyme is a complex protein, then it consists of a protein and non-discovered part. The protein part is a high molecular weight, thermolar part of the enzyme and is calledapophenimet . It has a peculiar structure and determines the specificity of enzymes.

Neechkaya part of the enzyme calledcofacitor (Correment) . The cofactor is most often metal ions that can firmly bind to the apocherment (for example,Zn. in the fermente carboanhydrase, withu. in the enzyme cytochromoxidase). The coenses are most often organic substances less firmly associated with the apocherment. Coenzymes are nucleotides over, Fad. Coenzyme- low molecular weight, thermostable part of the enzyme. Its role is that it determines the spatial laying (conformation) of the apophergement, and determines its activity. Cofactors can carry electrons, functional groups, participate in the formation of additional links between the enzyme and the substrate.

In functionality in the enzyme, it is customary to allocate two important areas in the enzyme molecule: the active center and the alto-separation site

Active Center - This is a portion of an enzyme molecule that interacts with the substrate and participates in the catalytic process. The active center of the enzyme is formed by amino acid radicals removed from each other in the primary structure. The active center has three-dimensional laying, most often in its composition detected

He is a group of serine

Sh - cysteine

NH 2 lysine

- γ -On glutamic acid

The active center distinguishes two zones - the binding zone with the substrate and the catalytic zone.

Binding zone It usually has a hard structure, which complements the reaction substrate complementary. For example, trypsin splits proteins in areas rich in a positively charged with lysine amino acid, since the residues of negatively charged aspartic acid are contained in its binding zone.

Catalytic zone -this is a plot of an active center directly affecting the substrate and carrying out a catalytic function. This zone is more mobile, it is possible to change the interjection of functional groups.

In a number of enzymes (more often oligomeric), except for the active center presentalosteric plot - The portion of the enzyme molecule, remote from the active center and interacting not with the substrate, but with additional substances (regulators, effectors). In alto-using enzymes, an active center may be in one subunit, in the other - alto-cell site. Alosteric enzymes change their activity as follows: The effector (activator, inhibitor) acts on the alto-satellite subunit and changes its structure. Then the change in the conformation of the altoworking subunit on the principle of cooperative changes is mediated by the structure of the catalytic subunit, which is accompanied by a change in the activity of the enzyme.

The mechanism of action of enzymes.

Enzymes have a number of general collaboratical properties:

• do not shift catalytic equilibrium
• not spent in the reaction process
• only thermodynamically real reactions catalyze. Such reactions are those in which the original energy supply of molecules is greater than the final one.

In the course of the reaction, a high energy barrier is overcome. The difference between the energy of this threshold and the initial energy level is the activation energy.

The rate of enzymatic reactions is determined by the activation energy and a number of other factors.

The rate constant of the chemical reaction is determined by the equation:

K \u003d P * Z * E - (EA / RT)

K - reaction rate constant

P - spatial (steric) coefficient

Z. - the number of interacting molecules

E A. - Activation energy

R. - Gas constant

T - universal absolute temperature

e - the basis of natural logarithms

In this equationZ, E, R, T - Permanent values, and P and EA - variables. Moreover, between the response rate and the steric coefficient, the dependence is straight, and between the speed and activation energy - inverse and power dependence (the lower the EA, the higher the reaction rate).

The mechanism of action of enzymes is reduced to an increase in the enzymes of a steric coefficient and a decrease in activation energy.

Reducing activation energy enzymes.

For example, the splitting energy2 O 2. Without enzymes and catalysts - 18,000 kcal per mol. If platinum and high temperature are used, it decreases to 12,000 kcal / mol. With the participation of the enzymecatalase The activation energy is only 2,000 kcal / mol.

The decrease in EA occurs as a result of the formation of intermediate enzyme-substrate complexes according to the scheme:F + S.<=> FS -complex → F + Reaction products. For the first time the possibility of forming enzyme substrate complexes was proved by Michaelis, and mentens. Subsequently, many enzyme-substrate complexes have been allocated. To explain the high selectivity of enzymes when interacting with the substrate proposedthe theory of "Key and Castle" Fisher. According to it, the enzyme interacts with the substrate only with absolute correspondence of their friend (complementaryness) like the key and the lock. This theory explained the specificity of enzymes, but did not reveal the mechanisms of their impact on the substrate. Later, the theory of induced conformity of the enzyme and substrate was developed -theory of Cattled. (Theory of "Rubber Glove"). Its essence is as follows: The active center of the enzyme is formed and contains all functional groups before interacting with the substrate. However, these functional groups are in inactive condition. At the time of joining the substrate, the perduties changes in the position, the structure of radicals in the active center of the enzyme. As a result, the active center of the enzyme under the action of the substrate enters the active state and, in turn, begins to influence the substrate, i.e. occursinteraction active center of the enzyme and substrate. As a result, the substrate passes into an unstable, unstable state, which leads to a decrease in activation energy.

The interaction of the enzyme and substrate may be in the reactions of nucleophilic substitution, electrical replacement, dehydration of the substrate. There is also a short-term covalent interaction of the functional groups of the enzyme with the substrate. Basically, the geometric reorientation of the functional groups of the active center occurs.

An increase in the enzymes of the steric coefficient.

The steric coefficient is introduced for reactions in which large molecules are involved having a spatial structure. The steric coefficient shows the proportion of successful collisions of active molecules. For example, it is 0.4, if 4 of the 10 collisions of the active molecules led to the formation of the reaction product.

Enzymes increase the steric coefficient, as they change the structure of the substrate molecule into the enzyme - the substrate complex, as a result of which the complementarity of the enzyme and the substrate increases. In addition, the enzymes at the expense of their active centers streamline the location of the substrate molecules in space (before interaction with the enzyme the substrate molecule are chaotic) and facilitate the flow of the reaction.

Nomenclature of enzymes

Enzymes have several types of titles.

1. Trivial names (tripsin, pepsin)
2. Working nomenclature. In this name of the enzyme there is an end - aza, which is added:
   • to the name of the substrate (sugar, amylase),
   • to the type of connection to which the enzyme (peptidase, glycosidase) is valid,
   • to the type of reaction, process (synthetase, hydrolase).

3) Each enzyme has a classification name, which reflects the type of reaction, the type of substrate and the coenzyme. For example: LDH -L lactate-over + - oxidoreduktase.

Classification of enzymes.

The classification of enzymes was developed in 1961. According to the classification, each enzyme is located in a specific class, a subclass, a pre-class and has a sequence number. In this regard, each enzyme has a digital cipher in which the first figure denotes the class, the second - subclass, the third - sub-class, the fourth is the sequence number (LDH: 1,1,1,27). All enzymes are classified into 6 classes.

1. Oxydoreduktase
2. Transferase
3. Hydrolase
4. Liaza
5. Isomerase
6. Synthetases (ligases)

Oxydoreduktase.

Enzymes catalyzing redox - recovery processes. General view of the reaction: AoK + in Break \u003d and Vost + in OK . This class of enzymes includes several subclasses:

1. Dehydroginases, Catalyze reactions by pulping hydrogen from an oxidized substance. They may be aerobic (tolerate hydrogen per oxygen) and anaerobic (transfer hydrogen not to oxygen, but for some other substance).

2. Oxygenase - Enzymes catalyzing oxidation by connecting oxygen to an oxidized substance. If one oxygen atom is attached, monooxygenases are involved, if two oxygen atoms are dioxigenase.

3. Peroxidase - Enzymes catalyzing oxidation of substances with the participation of peroxides.

Transferase.

Enzymes carrying out intramolecular and intermolecular transfer of functional groups from a substance to another according to the scheme: AV + C \u003d A + Sun. Transferase subclasses are isolated depending on the type of portable groups: aminotransferase, methyltransferase, sulfotransferase, acyltransferase (tolerate residues of fatty acids), phosphotransferase (tolerate phosphoric acid residues).

Hydrolase.

The enzymes of this class catalyze a gap of a chemical connection with the addition of water at the place of the break, that is, the hydrolysis reactions according to the scheme: Av + \u200b\u200bNon \u003d An + Won. The subclasses of hydrolyzes are isolated depending on the type of bonded bonds: peptidases are cleaved by peptide bonds (pepsin), glycosidases - glycosida bonds (amylase), Esterase - ester connections (lipase).

Liaza.

Liases catalyze a chemical break without joining water at a break point. At the same time, double bonds are formed in the substrates according to the scheme: Av \u003d A + V. The liaise subclasses depend on whether the connection is broken and which substances are formed. The aldolase breaks the relationship between two carbon atoms (for example, fructose 1,6-di-phosphathaldolaza "cuts" fructose and two triosis). Liazams include decarboxylase enzymes (cleavage of carbon dioxide), dehydrates - "cut out" water molecules.

Isomerase.

Isaorerase catalyze mutual solutions of various isomers. For example, phosphohexoisosemesis translates fructose into glucose. Isomerase subclasses include mutases (phosphoglucomuctase translates glucose-1-phosphate into glucose-6-phosphate), epimeresoses (for example, translate ribose to xylulose), tautomerase

Synthetases (ligases).

The enzymes of this class catalyze the reactions of the synthesis of new substances due to the energy of ATP according to the scheme: A + B + ATP \u003d AB. For example, glutamine substation connects glutamic acid,NH 3. + With the participation of ATP with the formation of glutamine.

Properties of enzymes.

Enzymes, in addition to common with inorganic catalysts, properties have certain differences from inorganic catalysts. These include:

• higher activity
• higher specificity
• softer conditions for catalysis
• ability to regulate activity

High catalytic enzyme activity.

Enzymes are distinguished by high catalytic activity. For example, one carboanhydrase molecule catalyzes the formation (or splitting) of 36 million carbonic acid molecules in one minute (n2 CO 3. ). The high activity of enzymes is explained by the mechanism of their action: they reduce the activation energy and increase the spatial (steric coefficient). The high activity of enzymes has an important biological value, which consists in ensuring the high speed of chemical reactions in the body.

High specificity enzymes.

All enzymes have specificity, but the degree of specificity in different enzymes is different. Several types of enzyme specificity are distinguished.

Absolute Substrate specificity at which the enzyme acts only on one particular substance. For example, the urease enzyme splits only urea.

Absolute group Specificity at which the enzyme has the same catalytic effect on a group of compounds close in structure. For example, an alcohol dehydrogenase enzyme oxidizes not only with2N 5. He, but also his homologues (methyl, butyl and other alcohols).

Relative groupspecificity at which the enzyme carries out the catalysis of different classes of organic substances. For example, trypsin enzyme shows peptidase and esstruse activity.

Stereochemicalspecificity (optical specificity), at which only a certain form of isomers is split (D, L. Forms, α, β, cis - transizometers). For example, LDH is valid only onL -Laktat, L - amino acid oxide act onL. - Amino acidisomers.

High specificity is explained unique for each enzyme structure of the active center.

Thermalness of enzymes.

Thermal content is the dependence of the activity of enzymes on temperature. When the temperature is raised from 0 to 40 degrees, the activity of enzymes is growing according to the VANT-Hoff rule (with an increase in temperature by 10 degrees, the reaction rate is increased by 2-4 times). With a further increase in temperature, the activity of enzymes begins to decrease, which is explained by the thermal denaturation of the protein enzyme molecule. Graphically thermo-dependence of enzymes has the form:

Inactivation of the enzyme at 0 degrees is reversible, and at high temperature, inactivation becomes irreversible. This property of enzymes determines the maximum reaction rate in human body temperature. Thermalness of enzymes should be taken into account in practical medical activities. For example, when conducting an enzymatic reaction in the tube, it is necessary to create an optimal temperature. This property of enzymes can be applied in cryoshurgery, when a complex long operation is carried out with a decrease in body temperature, which slows down the rate of reactions flowing in the body reduces the oxygen consumption by tissues. Store enzyme preparations are necessary under reduced temperature. For neutralization, the disinfection of microorganisms use high temperatures (autoclavation, boiling tools).

PhotoLability.

PhotoLatility - the dependence of the activity of enzymes from ultraviolet rays. UFL cause photodehanitation of protein molecules and reduce the activity of enzymes. This property of enzymes is used in the bactericidal effect of ultraviolet lamps.

Dependence of activity from pH.

All enzymes have a certain pH interval, in which the activity of the enzyme is maximal - the optimum pH. For many enzymes, the optimum is about 7. At the same time, for pepsin, the optimal medium 1-2, for alkaline phosphatase, about 9. When the pH is deviated from the optimum, the enzyme activity decreases, which is seen from the graph. This property of enzymes is explained by the change in the ionization of ionic groups in the enzyme molecules, which leads to a change in ionic ties in the molecule of the protein molecule of the enzyme. This is accompanied by a change in the conformation of the enzyme molecule, and this, in turn, leads to a change in its activity. In the conditions of the body of the pH - dependence determines the maximum activity of enzymes. This property finds and practical application. Enzymatic reactions outside the body are carried out at the optimum pH. With reduced acidity of gastric juice with therapeutic purposes prescribed a solution of NAl.

The dependence of the rate of the enzymatic reaction from the concentration of the enzyme and the concentration of the substrate

The dependence of the reaction rate from the concentration of the enzyme and the concentration of the substrate (the kinetics of enzymatic reactions) is represented on the charts.

Schedule 1 chart 2

In an enzymatic reaction (F + S 2  1 FS → 3 F + P) Select the speed of three components of the stages:

1- Education enzyme-substrate complexFS,

2-reverse decay enzyme - substrate complex,

3 - disintegration of the enzyme-substrate complex with the formation of reaction products. The speed of each of these reactions is subject to the law of the existing masses:

V 1 \u003d K 1 [F] * [s]

V 2 \u003d k 2 * [FS]

V 3 \u003d K 3 * [FS]

At the time of equilibrium, the rate of education reactionFS. equal to the sum of the speeds of its decay:V 1 \u003d V 2 + V 3. Of the three stages of the enzymatic reaction, the most important and slow is the third, Since it is associated with the formation of reaction products. According to the above formula, find speedV 3. it is impossible, since the enzyme-substrate complex is very unstable measuring its concentrations. In this regard, Michaelis-Menten introduced tom. - Mikhaelis constant and transformed an equation for measuringV 3. in a new equation, in which actually measurable values \u200b\u200bare present:

V 3 \u003d K 3 * [F 0] * [S] / KM + [S] or V 3 \u003d V MAX * [S] / KM + [S]

[F 0] - the initial concentration of the enzyme

To M. - Mikhailis Constant.

Physical meaning K.m: K M \u003d (K 2 + K 3) / K 1 . It shows the ratio of the disintegration rate of the enzyme-substrate complex and the rate constant of its formation.

The Mikhailisa Menten equation is universal. It illustrates the dependence of the reaction rate from [F 0] from [s]

1. The dependence of the reaction rate from the concentration of the substrate. This dependence is detected at low substrate concentrations [S]< Km . In this case, the concentration of the substrate in the equation can be neglected and the equation acquires the form:V 3 \u003d K 3 * [F 0] * [S] / KM. In this equationK 3, F 0], KM - constants and can be replaced with a new constant to *. Thus, at a low concentration of the substrate, the reaction rate is directly proportional to this concentration.V 3 \u003d k * * [s]. This dependence corresponds to the first section of the graph 2.
2. The dependence of the speed of the enzyme concentration It is manifested at high substrate concentration.S ≥ Km. . In this case, you can neglectKM. and the equation is converted to the following:V 3 \u003d k 3 * (([F 0] * [S]) / [S]) \u003d K 3 * [F 0] \u003d V MAX. Thus, with a high concentration of the substrate, the reaction rate is determined by the concentration of the enzyme and reaches the maximum value.V 3 \u003d k 3 [F 0] \u003d V Max. (Third Graphic Plot 2).
3. Allows you to determine the numerical valueKm under the condition V 3 \u003d V Max / 2. In this case, the equation acquires the form:

V MAX / 2 \u003d ((V MAX * [S]) / KM + [s ]), from where it follows thatKm \u003d [s]

Thus, to M Numerically equal to the concentration of the substrate at the reaction rate equal to half the maximum. TOm. is a very important characteristic of the enzyme, it is measured in a moles (10-2 - 10 -6 mole) and characterize the specificity of the enzyme: the lowerKM. The higher the specificity of the enzyme.

Graphic definition of the Mikhailis constant.

It is more convenient to use a graph representing a straight line. Such a schedule is proposed by the Linuiver - Berk (a graph of double reverse values), which corresponds to the opposite equation Mikhailis - Menten

The dependence of the speed of enzymatic reactions from the presence of activators and inhibitors.

Activators - Substances that increase the speed of enzymatic reactions. Distinguish specific activators that increase the activity of one enzyme (NAl. - Activator of pepsinogen) and nonspecific activators increasing the activity of a number of enzymes (ionsMG. - Activators of hexochinases, k,Na. -ATF-Ase and other enzymes). Metal ions, metabolites, nucleotides can be as activators.

Action mechanism of activators.

1. The completion of the active center of the enzyme, as a result of which the interaction of the enzyme with the substrate is facilitated. Such a mechanism has mainly metal ions.
2. The alto-solid activator interacts with the alto-satellite site (subunit) of the enzyme, through its changes indirectly changes the structure of the active center and increases the activity of the enzyme. Alosteric effect possess metabolites of enzymatic reactions, ATP.
3. Alosteric mechanism can be combined with a change in the oligomy of the enzyme. Under the action of the activator there is a combination of several subunits into an oligomeric form, which dramatically increases the activity of the enzyme. For example, isocitrate is an activator of the enzyme acetyl-co-carboxylase.
4. Phosphorization - dephospholization of enzymes relates to a reversible modification of enzymes. Joining N.3 PO 4. Most often sharply increases the activity of the enzyme. For example, two inactive phosphorylase enzyme dimers are connected to four ATP molecules and form an active tetramic phosphorylated form of the enzyme. The phosphorus of enzymes can be combined with the change in their oligomy. In some cases, the phosphorylation of the enzyme, on the contrary, reduces its activity (for example, phosphorylation of the enzyme glycogenesis)
5. Partial proteolysis (irreversible modification). In this case, the mechanism from the inactive form of the enzyme (proferment) fragment of the molecule, blocking the active center of the enzyme, is cleaved. For example, inactive pepsinogen under actionHCL Enters active pepsin.

Inhibitors - substances that reduce the activity of the enzyme.

By specificity Select specific and nonspecific inhibitors

In contact The effect distinguishes reversible and irreversible inhibitors.

At the place of action There are inhibitors operating at the active center and outside the active center.

By mechanism of action Break into competitive and non-competitive inhibitors.

Competitive inhibition.

Inhibitors of this type have a structure close to the structure of the substrate. By virtue of this, inhibitors and substrate compete for the binding of the active center of the enzyme. Competitive inhibition is a reversible inhibition of the effect of a competitive inhibitor can be reduced by increasing the concentration of the reaction substrate

An example of competitive inhibition can be the oppression of the activity of succinate dehydrogenase, catalyzing the oxidation of dicarboxylic acid dicarboxylic acid, dicarboxyle with minor acid, similar in structure with amber acid.

The principle of competitive inhibition is widely used when creating medicines. For example, sulfonamide preparations have a structure close to the structure of para-aminobenzoic acid necessary for the growth of microorganisms. Sulfanimamides block the enzymes of microorganisms necessary for the absorption of para-aminobenzoic acid. Some antitumor drugs are analogues of nitrogenous bases and, thus, inhibit nucleic acid synthesis (fluorouracil).

Graphically competitive inhibition is:

Non-competitive inhibition.

Non-competitive inhibitors structurally do not have similar to the substrates of reactions and therefore cannot be supplied with a high concentration of the substrate. There are several options for the action of non-competitive inhibitors:

1. Blocking the functional group of the active center of the enzyme and, as a result, reducing activity. For example, activityS. H - groups can bind thiol poices reversible (salts of metals, mercury, lead) and irreversible (monoiodalis). The effect of inhibition of thic inhibitors can be reduced by the introduction of additional substances richSh groups (for example, unitiol). There are and used serine inhibitors that block it - groups of the active center of enzymes. Such an effect is organic phosphorus-containing substances. These substances can, in particular, inhibit it - groups in the enzyme of acetylcholinesterase, which destroys the neurotiator of acetylcholine.
2. Blocking metal ions included in the active center of enzymes. For example, cyanides block iron atoms, EDTA (ethylenediaminetetraacetate) blocks SA ionsMG.
3. The altoworking inhibitor interacts with the alto-satellite site, indirectly through it according to the principle of cooperativeness, changing the structure and activity of the catalytic area. Graphically non-competitive inhibition has the form:

The maximum reaction rate with non-competitive inhibition cannot be achieved by increasing the concentration of the substrate.

Regulation of enzyme activity in the process of metabolism.

Adaptation of the body to changing conditions (power mode, environmental impacts, etc.) is possible due to the change in enzyme activity. There are several possibilities for regulating the speed of enzyme reactions in the body:

1. Changing the rate of synthesis of enzymes (this mechanism requires a long period of time).
2. An increase in the availability of the substrate and the enzyme by changing the permeability of cell membranes.
3. Changes in the activity of enzymes already existing in cells and tissues. This mechanism is carried out at high speed and is reversible.

In multistage enzymatic processes allocateregulatory, Key Enzymes that limit the total speed of the process. Most often it is the enzymes of the initial and final stages of the process. Changing the activity of key enzymes occurs in various mechanisms.

1. Alosteric mechanism:

1. Change the oligomy of the enzyme:

Monomers are not active ↔ oligomers active

1. Phosphorization - Defosphorylation:

Enzyme (inactive) + n3 PO 4. ↔ Phosphorylated active enzyme.

In the cells are widely distributed the auto-regulatory mechanism. The autorentulatory mechanism is, in particular, retroinding, in which the products of the enzymatic process oppress the initial stages enzymes. For example, high concentrations of purine and pyrimidine nucleotides oppress the initial synthesis in the stages.

Sometimes the initial substrates activate the final enzymes, in the diagram: the substrate A activatesF 3. . For example, the active form of glucose (glucose-6-phosphate) activates the final enzyme of glycogen synthesis from glucose (glycogenxintase).

Structural organization of enzymes in the cell

The coherence of metabolic processes in the body is possible due to the structural disunity of enzymes in cells. Separate enzymes are located in certain intracellular structures -complementation.For example, in the plasma membrane, the Potassium enzyme is active - sodium ATF-AZA. In mitochondria, the enzymes of oxidative reactions (succinate dehydrogenase, cytochromoxidase) are active. The core is active enzymes of nucleic acid synthesis (DNA polymerase). In lysosomes, the splitting enzymes of various substances (RNA - Aza, phosphatase and others are active.

The enzymes are most active in this cellular structure are calledindicative or marker enzymes. Their definition in clinical practice reflects the depth of structural damage to the tissue. Some enzymes are combined into polysimensional complexes, for example, a pyruvate dehydrogenase complex (MPC), which carries out the oxidation of pyruvic acid.

Principles of detection and quantitative determination of enzymes:

The detection of enzymes is based on their high specificity. Enzymes are detected by action produced by them, i.e. Upon the fact that the reaction that the enzyme catalyzes is catalyzed. For example, amylase is detected by the reaction of cleavage of starch to glucose.

The criteria for the flow of an enzymatic reaction can be:

• disappearance of the reaction substrate
• appearance of reaction products
• changes in the optical properties of the coenzyme.

Quantitative determination of enzymes

Since the concentration of enzymes in cells is very low, then they are not determined by their true concentration, but the number of enzyme is judged indirectly, according to the activity of the enzyme.

The activity of enzymes is estimated at the rate of an enzymatic reaction flowing under optimal conditions (the optimum temperature, pH, redundantly high concentration of the substrate). Under these conditions, the reaction rate is directly proportional to the concentration of the enzyme (V \u003d K 3 [F 0]).

Units of activity (quantity) enzyme

In clinical practice, several units of enzyme activity are used.

1. An international unit is the amount of enzyme that catalyzes the conversion of 1 micromol substrate per minute at a temperature of 250 S.
   1. Catying (in the SI) - then the amount of enzyme that catalyzes the conversion of 1 praying substrate per second.
   2. Specific activity - the ratio of the activity of the enzyme to the mass of the protein of the enzyme.
   3. The molecular activity of the enzyme shows how many substrate molecules turns under the action of 1 enzyme molecule.

Clinical enzymeology

The application of information about enzymes in medical practice is a section of medical enzymology. It includes 3 sections:

1. Enzymodiagnostic
   1. Enzymopotology
      1. Enzymotherapy

Enzymodiagnostics - The section that studies the ability to study the activity of enzymes for disease diagnosis. To assess damage to individual tissues, organ-specific enzymes, isoenzymes are used.

In pediatric practice, during the enzyme diagnostics, children's features must be taken into account. In children, the activity of some enzymes is higher than in adults, for example, high LDH activity reflects the predominance of anaerobic processes in the early postnatal period. The content of transaminase in the blood plasma of children is raised as a result of increased vascular fabric permeability. The activity of glucose-6-phosphate dehydrogenase increased as a result of the reinforced decay of the erythrocytes. The activity of other enzymes, on the contrary, is lower than in adults. For example, pepsin activity, pancreatic enzymes (lipase, amylase) reduced by virtue of the immaturity of secretory cells.

With age, the redistribution of individual isoenzymes is possible. So, children prevailing LDH3 (more anaerobic form), and in adults LDH2 (more aerobic form).

Enzymopathology - The section of enzymology, studying the disease, the leading development mechanism of which is the violation of the activity of enzymes. These include violations of carbohydrate metabolism (galactosemia, glycogenesis, mucopolysaccharideosis), amino acids (phenylketonuria, cystinuria), nucleotides (orotata), porphyrins (porphyria).

Enzymotherapy - Section of enzyme studies studying the use of enzymes, coenzymes, activators, inhibitors with therapeutic purposes. Enzymes can be used with the substitution goal (pepsin, pancreatic enzymes), with a lytic goal for removing necrotic mass, thrombov, to disperse viscous exudates.

Literature

1. Avdeeva, L.V. Biochemistry: Tutorial / L.V. Avdeeva, T.L. Aleinikova, L.E. Andrianova; Ed. E.S. Severin. - M.: Gootar-Honey, 2013. - 768 c.

2. Auerman, T.L. Basics of biochemistry: Tutorial / T.L. Auerman, T.G. Generalova, G.M. Suslamans. - M.: Ince Infra-M, 2013. - 400 c.

3. Bazaarnova, Yu.G. Biochemical bases of processing and storage of raw materials of animal origin: Tutorial / Yu.G. Bazaarnova, i.e. Burova, V.I. Marchenko. - SPb.: Prosp. Science, 2011. - 192 c.

4. Baishev, I.M. Biochemistry. Test questions: Tutorial / D.M. Zubairov, I.M. Baishev, R.F. Bikeev; Ed. D.M. Tubirov. - M.: Goeotar Media, 2008. - 960 C.

5. Go, S.B. Biochemistry of phylogenesis and ontogenesis: Tutorial / A.A. Chirkin, E.O. Danchenko, S.B. Go Under total. ed. A.A. Chirkin. - M.: NIC infra-M, new. Knowledge, 2012. - 288 c.

6. Hydranovich, V.I. Biochemistry: Tutorial / V.I. Hydranovich, A.V. Hydrananovich. - MN: Tetrasystem, 2012. - 528 c.

7. Golochepov, A.P. Genetic and biochemical aspects of person's adaptation to the conditions of the city with a developed chemical industry / A.P. Holochapov. - M.: KMK, 2012. - 103 c.

8. Gunkova, P.I. Biochemistry of milk and dairy products / KK Gorbatova, P.I. Gunkova; Under total. ed. Kk Gorbatov. - SPb.: Gore, 2010. - 336 c.

9. Dimitriev, A.D. Biochemistry: Tutorial / A.D. Dimitriev, E.D. Ambrosyeva. - M.: Dashkov and K, 2013. - 168 c.

10. Ershov, Yu.A. General biochemistry and sport: Tutorial / Yu.A. Ershov. - M.: Moscow State University, 2010. - 368 C.

11. Ershov, Yu.A. Basics of biochemistry for engineers: Tutorial / Yu.A. Ershov, N.I. Zaitseva; Ed. S.I. Schukin. - M.: MSTU them. Bauman, 2010. - 359 c.

12. Kamyshnikov, V.S. Handbook on clinical and biochemical laboratory diagnostics: in 2 volumes. In the 2-T.Spolymer on clinical and biochemical laboratory diagnostics: in 2 volumes / V.S. Wovers. - MN: Belarus, 2012. - 958 c.

13. Klopov, M.I. Biologically active substances in physiological and biochemical processes in the animal organism: Tutorial / M.I. Klopov, V.I. Maximov. - SPb.: Lan, 2012. - 448 c.

14. Mikhailov, S.S. Sports biochemistry: Textbook for universities and colleges of physical culture / S.S. Mikhailov. - M.: OV. Sport, 2012. - 348 c.

15. Repnikov, B.T. Products and biochemistry of fishing goods: Tutorial / B.T. Repicks. - M.: Dashkov and K, 2013. - 220 c.

16. Rogozhin, V.V. Biochemistry of milk and meat: textbook / V.V. Rogozhin. - SPb.: Gore, 2012. - 456 c.

17. Rogozhin, V.V. Plant biochemistry: Textbook / V.V. Rogozhin. - SPb.: Gore, 2012. - 432 c.

18. Rogozhin, V.V. Workshop on physiology and biochemistry of plants: Tutorial / V.V. Rogozhin, T.V. Rogozhina. - SPb.: Gore, 2013. - 352 c.

19. Taganovich, A.D. Pathological biochemistry: monograph / A.D. Taganovich. - M.: Binom, 2013. - 448 c.

20. Filippovich, Yu.B. Biochemical Basics of Human Life: Tutorial for University Students / Yu.B. Filippovich, A.S. Konichev, G.A. Sevastyanova, N.M. Kutuzov. - M.: Vlados, 2005. - 407 c.

21. Shcherbakov, V.G. Biochemistry and mercy of oilseeds / V.G. Shcherbakov, V.G. Lobanov. - M.: Koloss, 2012. - 392 c.

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Enzymes, or enzymes (from lat. Fermentum - Zakvaska) - Usually protein molecular molecularimolecules RNA (ribozymes) or their complexes, accelerating (catalyzing) chemical reactions of live systems. The agent of the reaction catalyzed by enzymes is called suspores, and the resulting substances are products. Enzymes are specific to substrates (ATPAZ catalyzes splitting only ATP, and kinase phosphorylazyphosphorilates is phosphorylase).

Enzymatic activity can be regulated by activators inhibitors (activators - increase, inhibitors are lowered).

Protein enzymesintezes are noribosomes, and RNA is in the kernel.

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-speaking).

The science of enzymes is called enzymologyrather than enzymes (in order not to mix the roots of the words of Latin and Greek languages).

Study history

Term enzyme Proposed in the XVII century Chemist Van Gelmontompriri discussion of the mechanism.

In con. XVIII - Nach. XIX centuries. It has already been known that meat is digested by gastric juice, the accrehension of saliva accumulates the accumulation of saliva. However, the mechanism of these phenomena was unknown.

In the XIX century Louis Pasteur, studying the transformation of the exedroggy, reached the conclusion that this process (fermentation) is catalyzed by some vital power in yeast cells.

Over a hundred years ago Terms enzyme and enzyme Reflected various points of view in the theoretical dispute L. Pasteras one hand, im. Bertloyia. Lubiha - on the other, about the nature of alcohol fermentation. Actually enzymes (from lat. fermentum - Zakvaska) called "organized enzymes" (that is, living microorganisms themselves), and the term enzyme (from the Greek.ἐν- - and ύύμη - yeast, Zakvaska) proposed in 1876 year. Kyun for "unorganized enzymes" secreted by cells, for example, in the stomach (pepsin) or intestines (tripsin, amylase). Two years after the death of L. Pasteur B1897. Bukchner Published "Alcohol fermentation without yeast cells", in which experimentally showed that the cell-free yeast juice carries out alcohol fermentation as well as non-destructive yeast cells. In 1907, this work he was awarded the Nobel Prize. For the first time, the highly purified crystal enzyme (ureaza) was highlighted in 1926. Samner. Over the next 10 years, several more enzymes were allocated, and the protein nature of enzymes was finally proven.

The catalytic activity of RNA was first discovered in the 1980s at Pre-RDNA Thomas Chekch, studiousSpilsingRNA Winfuzoria Tetrahymena Thermophila.. The ribozymomocael to the TETRAHYMENA pre-RRNA molecule section, the coding internal RDNA genes; This plot carried out autosplaxing, that is, she cut itself when ripening RRNA.

Enzyme functions

Enzymes are present in all living cells and contribute to the transformation of one substances (substrates) to other (products). Enzymes act as catalysts in almost all biochemical reactions occurring in living organisms. By 2013, more than 5,000 different enzymes were described. They play a crucial role in all the processes of vital activity, directing and regulating the exchange of substance and organization.

Like all catalysts, enzymes accelerate both direct and reverse reaction, lowering the energy of the activation of the process. Chemical equilibrium is not shifted in direct or in the opposite direction. A distinctive feature of enzymes compared to non-discontinuity catalysts is their high-resistant-constant binding substrates with protein can reach 10 -10 mol / l and less. Each enzyme molecule is capable of performing from several thousand to several million operations per second.

For example, one renin enzyme molecule contained in the gastric mucous membrane of the challenge, about 10 6 milk casinogenic molecules in 10 minutes at 37 ° C.

At the same time, the effectiveness of enzymes is significantly higher than the effectiveness of non-protein catalysts - enzymes accelerate the reaction to millions and billions of times, non-discovered catalysts - hundreds and thousands of times. See also catalytically perfect enzyme

Classification of enzymes

According to the type of catalyzed reactions, enzymes are divided into 6 classes according to the hierarchical classification of enzymes Classification was proposed by the International Union of Biochemistry and Molecular Biology. Each class contains subclasses, so the enzyme is described by a set of four numbers separated by points. For example, the pepsinimet is the name of the EU 3.4.23.1. The first number is rudely describes the reaction mechanism catalyzed by the enzyme:

CF 1: Oxydoreduktasecatalyzing oxidation or recovery. Example: catalase, alcoholicdegeryenaz.

CF 2: Transferase, catalyzing the transfer of chemical groups with one substrate molecule another. Among the transfers are highly highlighted by cellinases carrying phosphate groups, as a rule, with molecules.

KF 3: Hydrolasecatalyzing hydrolyzhemical bonds. Example: Esterase, pepsin, trypsin, amylase, lipoproteinlipase.

KF 4: Liaza, catalyzing the tear of chemical bonds without hydrolysas formation of the formation of one of the products.

CF 5: Isomerasecatalyzing structural or geometric changes in the substrate molecule.

CF 6: Ligasescatalyzing the formation of chemical ties between substrates due to hydrolysis ATP. Example: DNA polymerase.

Oxy subcutase - these are enzymes, catalyzing oxidation and recovery reactions, i.e. Transfer of electrons from the donor to the acceptor. Oxidation is the exclusion of hydrogen atoms from the substrate, and the restoration is the addition of hydrogen atoms to the acceptor.

Oxidoreductases include: dehydases, oxidases, oxygenase, hydroxylase, peroxidase, catalase. For example, enzymal refereyhydrogenasa is a reaction to the conversion of alcohol into aldehyde.

Oxy subcatases carrying a hydrogen atom or electrons directly to oxygen atoms are called aerobic dehydrogenases (oxidases), while oxidoreductase, carrying hydrogen atom or electrons from one component of the heating chain of enzymes to another, are called anaerobic dehydrogenases. A common variant of the oxidation-reduction process in cells is the oxidation of the hydrogen atoms of the substrate with the participation of oxy submission. Oxidoreduktases are two-component enzymes, in which the same coenzyment can contact various apopenis. For example, many oxidoreduktases as a coenzyme contain OED and NADP. At the end of a numerous class of oxy submission (in 11 positions), catalase and peroxidase enzymes are located. Of the entire number of proteins peroxysis cells, up to 40 percent are in catalase. Catalase and peroxidase split hydrogen peroxide in the following reactions: H2O2 + H2O2 \u003d O2 + 2N2O H2O2 + HO - R - OH \u003d O \u003d R \u003d O + 2H2O from these equations immediately become visible both an analogy and a significant difference between these reactions and enzymes. . In this, the deletelase splitting of hydrogen peroxide is a special case of peroxidase reaction, when hydrogen peroxide serves as a substrate, and the acceptor in the first reaction.

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

Reactions catalyzed by transfer, in the general case look like this:

A-X + B ↔ A + B-X.

Molecule A.here acts as a donor of the group of atoms ( X.) and molecule B.it is a group acceptor. Often, one intelligence protrusion as a donor in such transfer reactions. Many of the reaction catalyzed by transfer are reversible. The systematic names of the class enzymes are formed according to the scheme:

"Donor: acceptor + group + transferase».

Or a little more general names are used when the name of the enzyme is included in the name of either the donor or the group acceptor:

"Donor + group + transferase"Or" acceptor + group + transferase».

For example, athe moleculic acid coholmic group, Catechol-o-permanent of the IS-adenosylmethionine carrier group onto a benzene ring of different clampocholamines, aguetyl-acetyltransferazerosperosisitis a acetyl group from acetyl coenzyme A nagiston in the activation process of activation transcription.

In addition, the enzymes of 7 subgroupransferrase carrying the residue of phosphoric acid, using phosphate group of phosphate group, is often called kinases; aminotransferase (6 subgroup) often called transaminases

Hydrolase (CF3) is a class of catalyzing fluorescent communication. The general type of reaction catalyzed by hydrolase looks like this:

A-B + H 2 O → A-OH + B-H

The systematic name hydrolylase includes the name is splittingsubstrate followed by adding -Hyndolaza. However, as a rule, in the trivial title, the word hydrolylase is lowered and only suffix "-AZ" remains.

The most important representatives

Esterase: nuclease, phosphodiesterase, lipase, phospotase;

Glycosidases: amylase, lysozyme, etc.;

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

Acid anhydride hydrolase (Heliac, GTFAZ)

Being catalysts, enzymes accelerate both direct and reverse reaction, therefore, for example, liases are capable of catalyze and reverse reaction - connections for double bonds.

Liaza - a separate class of enzymes, catalyzing reactions of nonhehydrolitic and non-oxidative rupture of various chemical bonds ( C-C., C-O., C-N., C-S. and other) substrate, reversible reactions of formation and breaking of double bonds, accompanied by cleavage or addition of groups of atoms at its place, as well as the formation of cyclic structures.

In general, the name of the enzymes is formed according to the scheme " substrate + Liaza. " However, more often in the title takes into account the subclass of the enzyme. Liases differ from other enzymes in that two substrates are involved in the catalyzed reactions in one direction, and only one in the reverse reaction. In the name of the enzyme, there are words "decarboxylase" and "aldolaza" or "liaza" (pyruvate decarboxylase, oxalate-decarboxylase, oxaloacetate decarboxylase, threonine-aldolaza, phenylserin-aldolaza, isocitrate Liaza, Alanin Liaza, ATP-Citrate Liaza et al.), and for enzymes, catalyzing water cleavage reactions from the substrate - "dehydrates" (carbonate dehydrate, citrate dehydrate, serine dehydrates, etc.). In cases where only the reverse reaction was detected, or this direction in the reactions is more substantially, the word "synthase" (synthase mat-syntax, 2-isopropylmalate-synthase, citrate, hydroxymethyluutaryl-coa-synthasis, etc. is trimmed in the name of enzymes. .

Examples: histidydhecarboxylase, fumaratehydrate.

Isomerase - Enzymes, catalyzing transformations (racemic or epimerization). Isaorerase catalyzingRections, similar to the following: A → B, where B is an isomer A.

In the name of the enzyme there is a word " ratsumaza"(Alanin-Racecazaza, methionine-racemaza, hydroxyproline-racemaza, lactate-racemaza, etc.)," epimaza"(Almose-1-epimerase, ribuloseophosphate-4-epimemesis, UDF glucuronate-4-epimeresas, etc.)," isomerase"(Ribosophosphate-isomerase, xylose-aisomerasis, glucosamine phosphate-isomerase, Enoyo-Soo Isomeraz, etc.)," mutaza"(Phosphoglycerat-mutase, methilaspartate mutasis, phosphoglucomuutazai dr.).

Ligase (Lat. ligāre. - sew, connect) - enzyme, catalyzing compound of two molecules to form a new chemical bond ( ligation ). At the same time, a small chemical group from one of the molecules usually takes place (hydrolysis).

Ligases refer to EC 6 enzymes.

In the molecular biology of the ligase subclass 6.5 is classified on RNA ligases and DNA ligases.

DNA ligase

DNA ligase carrying reparationDank

DNA ligase - enzymes (EC 6.5.1.1), catalyzed by a stagnation of the roofing of the root of entrepreneurs, reparations. They form phosphodieter bridges between 5 "-phosphorile and 3" -gidroxyl groups of neighboring seasinucleotide discontinuities of the DNA break or between two DNA molecules. For the formation of these bridges, ligases use energetythdrolization-pyrofosphorylial connection. One of the most common commercially available enzymes - DNA ligasebacteriophagat4.

Mammamine DNA Ligases

Mammals class three main types of DNA ligases.

DNA Ligase I Lignites Fragments Protecting the Khodogenic Establishing DNA chain and participates in the excision reparation.

DNA ligase III in a complex with protein XRCC1 has a vaccision reparation in recombination.

DNA Ligase IV in the complex with the XRCC4Talizes the final stage of the non-homo-homoLogous end joining - nhej) of the DNA bunk gaps. It is also required for V (D) J enzymemunoglobulin recombination.

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

Enzyme name agreements

Usually enzymes are called the type of catalyzed reaction, adding suffix -Aza to the name of the substrate ( eg, lactase-enzyme involved in transformation). Thus, various enzymes performing one function will be the same name. Such enzymes differ in other properties, for example, by optimalph (alkaline phosphatase) or localization in the cell (membraneat phase).

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 amino acid chain, which is folded in a certain way. Each sequence of amino acids is cooled by a special way, and the resulting molecule (protein globule) has unique properties. Several protein chains can be combined into a protein complex. Taken structures are destroyed when heated or exposed to certain chemicals.

Active Center Enzymes

The study of the mechanism of the chemical reaction catalyzed by the enzyme along with the definition of intermediate and final products at different stages of the reaction involves the exact knowledge of the geometry of the tertiary structure of the enzyme, the nature of the functional groups of eggatives that ensure the specificity of the action and the high catalytic activity on the DVTsubstrat, as well as the chemical nature of the area (sections) of the molecule The enzyme that provides high catalytic reaction speed. Usually the substrate molecules involved in enzymatic reactions compared with enzyme molecules have relatively small sizes. Thus, in the formation of enzyme substrate complexes in direct chemical interaction, only limited fragments of the amino acid sequence of the polypeptide chain are entering - the "Active Center" - a unique combination of amino acid residues in the enzyme molecule, providing direct interaction with the substrate molecule and directly participate in the act of catalysis.

In the active center, it is conventionally distinguished:

catalytic center - directly chemically interacting with the substrate;

binding Center (Contact or "Anchor" Playground) - providing specific affinity for substrate and form a complex-substrate complex.

To catalyze the reaction, the enzyme must contact one or more substrates. The protein chain of the enzyme is collapsed in such a way that the slot is formed on the surface of the globule, or the substrates are applied. This area is called a substrate binding site. Usually it coincides with the active center of the enzyme or is close to it. Some enzymes also contain cofactor binding sites of metal ions.

Enzyme connecting with substrate:

cleans the substrate from water "fur coats"

there is a reacting substrate molecules in space necessary for the reaction

prepares for the reaction (for example, polarizes) the substrates molecules.

Usually the addition of the enzyme to the substrate occurs due to ionic or hydrogen bonds, rarely - due to covalent. At the end of the reaction, its product (or products) is separated from the enzyme.

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

In the absence of the enzyme:

In the presence of the enzyme:

• AF + B \u003d AVF

  AVF \u003d AV + F

where and in - substrates, AV is a reaction product, f - enzyme.

Enzymes cannot independently provide energy Endergonic reactions (for the flow of which energy is required). Therefore, enzymes that carry out such reactions may match them with exercion reactions that are highlighted with a larger amount of energy. For example, the synthesis reactions biopolymerically conjure with the reaction of Tidrolisatf.

For active centers of some enzymes, the phenomenon of cooperativeness is characteristic.

Specificity

Enzymes usually show high specificity in relation to their substrates (substrate specificity). This is achieved by partial complementarity of the shape, the distribution of charges and hydrophobic areas on the substrate molecule and at the center of the substrate binding on the enzyme. Enzymes usually demonstrate a high level of stereospeciff (form only one of the possible stereoisomer as a substrate as a substrate or is used as a substrate only one stereoisomer), regioselectivity (formed or tear the chemical bond only in one of the possible positions of the substrate) and chemoselectivity (only one chemical reaction catalyze Of several possible conditions for these conditions). Despite the overall high level of specificity, the degree of substrate and the reaction specificity of enzymes may be different. For example, the endopepidaztitripsinizes the peptide bond only after passagininyllylizin, if nimi should not be proline, the Appsing is less specific and can tear the peptide relationship following many amino acids.

In 1890, Emil Fisheropred himself that the specificity of enzymes is determined by the exact correspondence of the form of the enzyme and substrate. Such an assumption is called the "Key Castle" model. The enzyme is connected to the substrate with the formation of a short-lived enzyme-substrate complex. However, although this model explains the high specificity of enzymes, it does not explain the phenomena of stabilizing the transition state, which is observed in practice.

Model induced compliance

In 1958, Deniel Costepped the modification of the "Key Castle" model. Enzymes are mainly not rigid, and flexible molecules. The active center of the enzyme can change the conformation after binding the substrate. The lateral groups of amino acids of the active center take such a position that allows the enzyme to perform its catalytic function. In some cases, the substrate molecule also changes the conformation after binding in the active center. Unlike the "Key Castle" model, an induced conformity model explains not only the specificity of enzymes, but also stabilization of the transition state. This model was named "Hand-glove".

Modifications

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

Another common type of posttransmission modifications is the splitting of the polypeptide chain. For example, chymotrypsin (protease, which participates in an apparer) is obtained by leaving the polypeptide plot from chymotrypsinogen. Hymmotrygenogen is an inactive predecessor of chymotrypsin and is synthesized by the jigsaler. Inactive form is transported by the chorel, where it turns into chymotrypsin. Such a mechanism is necessary in order to avoid the splitting of the pancreas and other tissues before entering the enzyme in the stomach. Inactive predecessor of the enzyme is also called "wintering".

Cofactors enzymes

Some enzymes perform a catalytic function by themselves, without any additional components. However, there are enzymes that are necessary for the implementation of catalysis. Cofactors can be both inorganic molecules (metal ions, iron-sulfur clusters, etc.), and organic (for example, Flaviniligim). Organic Cofackers, firmly related to the enzyme, are also called prosthetic groups. Organic Cofackers, capable of separating the enzyme, are called coecments.

An enzyme that requires a cofactor for manifestation of catalytic activity, but is not associated with it, called the apoth enzyme. The apoth enzyme in the complex with the cofactor is called the holo-enzyme. Most cofactors are associated with an enzyme with non-covalent, but rather strong interactions. There are such prosthetic groups that are associated with an enzyme covalently, for example, thiaminepyrophosphate in pyruvate dehydrogenase.

Regulation of the enzymes

Some enzymes have small molecules binding sites, they can be substrates or the products of the metabolic path, which enters the enzyme. They reduce or increase the activity of the enzyme, which creates an opportunity for feedback.

Inhibition of finite product

Metabolic pathway - chain of consecutive enzymatic reactions. Often the final product of the metabolic pathway is an enzyme inhibitor accelerating the first of the reactions of this metabolic path. If the final product is too much, then it acts as an inhibitor for the very first enzyme, and if after this end product has become too small, then the first enzyme is activated again. Thus, inhibiting the final product according to the principle of a negative feedback method of supportingGometaz (the relative constancy of the conditions of the internal environment of the body).

Effect of environmental conditions on enzyme activity

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

Multiple forms of enzymes

Multiple forms of enzymes can be divided into two categories:

Isoenzymes

Actually multiple forms (true)

Isoenzymes - These are the enzymes whose synthesis is encoded by different genes, they have a different primary structure and different properties, but they catalyze the same reaction. Types of isoenzymes:

Organ - enzymes of glycoilizing liver and muscles.

Cellular - Malathedhydrogenazcitoplasmic and mitochondrial (different enzymes, but catalyze the same reaction).

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

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

Almofers are encoded by different alleles of the same gene.

Actually multiple forms (True) is the enzymes whose synthesis is encoded by the same allele of the same gene, they have the same primary structure and properties, but after synthesis on ribosomacone, modifications are subjected and become different, although they catalyze the same reaction.

The isoenzymes are different at the genetic level and differ from the primary sequence, and true multiple forms become different in the post-translation level.

Medical meaning

The relationship between enzymes and hereditary metabolic diseases was first established by A. Garrod in the 1910s. Garrod called diseases associated with enzyme defects, "congenital metabolic errors".

If a mutation is occurring in a gene encoding a certain enzyme, an amino acid sequence of the enzyme may change. At the same time, as a result of most mutations, its catalytic activity decreases or completely disappears. If the body receives two such mutant genes (one from each of each of the parents), the body ceases to go, which catalyzes this enzyme. For example, the appearance of albinos is associated with the cessation of the production of tyrosinase enzyme, which is responsible for one of the stages of the synthesis of the dark pigment of melanin. Phenylketonurium-based with a reduced or absent activity of the enzyme phenylalanine-4-hydroxylase enzyme in the liver.

Currently known hundreds of hereditary diseases associated with enzyme defects. Methods of treating and preventing many of these diseases have been developed.

Practical use

Enzymes are widely used in the national economy - food, textile industry, in pharmacology and medicine. Most drugs affect enzymatic processes in the body, launching or suspending certain reactions.

Even more widely using enzymes in scientific research and medicine.

Enzymes, organic substances of protein nature, which are synthesized in cells and increase the reaction flowing into them many times, without being subjected to chemical transformations. Substances that have a similar effect exist in inanimate nature and are called catalysts.

Enzymes (from lat. Fermentum - fermentation, Racing) are sometimes called enzymes (from Greek EN - inside, ZYME - Zervaska). All living cells contain a very large set of enzymes, whose catalytic activity depends on the functioning of cells. Almost each of the many diverse reactions occurring in the cell requires the participation of a specific enzyme. The study of the chemical properties of enzymes and catalyzed reactions is engaged in the special, very important area of \u200b\u200bbiochemistry - enzymology.

Many enzymes are in a cell in a free state, being simply dissolved in the cytoplasm; Others are associated with complex highly organized structures. There are enzymes, normally located outside the cell; Thus, enzymes catalyzing the cleavage of starch and proteins are secreted by the pancreas in the intestine. Secreter enzymes and many microorganisms.

Enzyme action

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

Thus, enzymes involved in cellulose synthesis are found in vegetable, but not in animal cells. Thus, it is important to distinguish between "universal" enzymes and enzymes specific for certain cell types. Generally speaking, the more cell specializes, the greater the likelihood that it will synthesize the set of enzymes needed to perform a particular cell function.

The feature of enzymes is that they have high specificity, i.e., can accelerate only one reaction or the reaction of the same type.

In 1890, E. G. Fisher suggested that this specificity is due to a special form of a enzyme molecule, which exactly corresponds to the form of a substrate molecule. This hypothesis got the name "key and lock", where the key is compared with the substrate, and the castle with the enzyme. The hypothesis reads: the substrate comes to the enzyme, as the key fits the castle. The selectivity of the enzyme is related to the structure of its active center.

Enzyme activity

First of all, the temperature of the enzyme affects the temperature. With an increase in temperature, the rate of chemical reaction increases. The speed of molecules increases, they appear more chances to face each other. Consequently, the likelihood that the reaction between them will increase. The temperature providing the greatest activity of the enzyme is optimal.

Outside the optimal temperature, the reaction rate decreases due to denaturation of proteins. When the temperature decreases, the chemical reaction rate also falls. At that moment, when the temperature reaches the freezing point, the enzyme is inactivated, but it does not denatrate.

Classification of enzymes

In 1961, a systematic classification of enzymes on 6 groups was proposed. But the names of enzymes were very long and difficult in pronunciation, so enzymes are customary to be called with the help of working names. The working name consists of the name of the substrate, which is valid for the enzyme, and the end of the "AZA". For example, if the substance is lactose, that is, milk sugar, then lactase is an enzyme that converts it. If sucrose (ordinary sugar), then the enzyme that splits it is sugar. Accordingly, enzymes that split proteins are called proteinase.

· Enzyme action structure and mechanism · Multiple forms of enzymes · Medical significance · Practical use · Notes · Literature & Middot

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

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

Active Center Enzymes

The study of the mechanism of the chemical reaction catalyzed by the enzyme along with the determination of intermediate and final products at different stages of the reaction implies the exact knowledge of the geometry of the tertiary structure of the enzyme, the nature of the functional groups of its molecule, providing specificity and high catalytic activity on this substrate, and besides this chemical nature of the site ( Sections) enzyme molecules, which provides high catalytic reaction speed. Usually the substrate molecules involved in enzymatic reactions compared with enzyme molecules have relatively small sizes. Thus, in the formation of enzyme substrate complexes in direct chemical interaction, only limited fragments of the amino acid sequence of the polypeptide chain are entering - the "Active Center" - a unique combination of amino acid residues in the enzyme molecule, providing direct interaction with the substrate molecule and directly participate in the act of catalysis.

In the active center, it is conventionally distinguished:

• catalytic center - directly chemically interacting with the substrate;
• binding Center (Contact or "Anchor" Playground) - providing specific affinity for substrate and form a complex-substrate complex.

To catalyze the reaction, the enzyme must contact one or more substrates. The protein chain of the enzyme is collapsed in such a way that the slot is formed on the surface of the globule, or the substrates are applied. This area is called a substrate binding site. Usually it coincides with the active center of the enzyme or is close to it. Some enzymes also contain cofactor binding sites or metal ions.

Enzyme connecting with substrate:

• cleans the substrate from water "fur coats"
• there is a reacting substrate molecules in space necessary for the reaction
• prepares for the reaction (for example, polarizes) substrate molecules.

Usually the addition of the enzyme to the substrate occurs due to ionic or hydrogen bonds, rarely - due to covalent. At the end of the reaction, its product (or products) is separated from the enzyme.

As a result, the enzyme reduces the activation energy of the reaction. This is because in the presence of the enzyme the reaction is on another path (the other reaction occurs in fact), for example:

In the absence of the enzyme:

• A + B \u003d av

In the presence of the enzyme:

• A + f \u003d af
• AF + B \u003d AVF
• AVF \u003d AV + F

where and in - substrates, AV is a reaction product, f - enzyme.

Enzymes cannot independently provide energy Endergonic reactions (for the flow of which energy is required). Therefore, enzymes that carry out such reactions may match them with exercion reactions that are highlighted with a larger amount of energy. For example, the biopolymer synthesis reactions are often conjugated with a response of ATP hydrolysis.

For active centers of some enzymes, the phenomenon of cooperativeness is characteristic.

Specificity

Enzymes usually show high specificity in relation to their substrates (substrate specificity). This is achieved by partial complementarity of the shape, the distribution of charges and hydrophobic areas on the substrate molecule and at the center of the substrate binding on the enzyme. Enzymes usually demonstrate a high level of stereospeciff (form only one of the possible stereoisomer as a substrate as a substrate or is used as a substrate only one stereoisomer), regioselectivity (formed or tear the chemical bond only in one of the possible positions of the substrate) and chemoselectivity (only one chemical reaction catalyze Of several possible conditions for these conditions). Despite the overall high level of specificity, the degree of substrate and the reaction specificity of enzymes may be different. For example, endopepidase trypsin breaks a peptide bond only after arginine or lysine, if nims should not be proline, and pepsin is much less specific and can break the peptide communication, following many amino acids.

Model "Key Castle"

In 1890, Emil Fisher suggested that the specificity of enzymes is determined by the exact correspondence of the form of the enzyme and substrate. Such an assumption is called the "Key Castle" model. The enzyme is connected to the substrate with the formation of a short-lived enzyme-substrate complex. At the same time, despite the fact that this model explains the high specificity of enzymes, it does not explain the phenomena of stabilizing the transition state, which is observed in practice.

Model induced compliance

In 1958, Denel Koshland suggested a modification of the "Key Castle" model. Enzymes are mainly not rigid, and flexible molecules. The active center of the enzyme can change the conformation after binding the substrate. The lateral groups of amino acids of the active center take such a position that enables the enzyme to perform its catalytic function. In some cases, the substrate molecule also changes the conformation after binding in the active center. Unlike the "Key Castle" model, an induced conformity model explains not only the specificity of enzymes, but also stabilization of the transition state. This model was named "Hand-glove".

Modifications

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

Another common type of posttransmission modifications is the splitting of the polypeptide chain. For example, chymotrypsin (protease, participating in digestion), is obtained by leaving the polypeptide portion from chymotrypsinogen. Hymputrygenogen is an inactive predecessor of chymotrypsin and is synthesized in the pancreas. Inactive form is transported in the stomach, where it turns into chymotrypsin. Such a mechanism is necessary in order to avoid the splitting of the pancreas and other tissues before entering the enzyme in the stomach. Inactive predecessor of the enzyme is also called "wintering".

Cofactors enzymes

Some enzymes perform a catalytic function by themselves, without any additional components. However, there are enzymes that are necessary for the implementation of catalysis. Cofackers can be both inorganic molecules (metal ions, iron-sulfur clusters, etc.) and organic (for example, flavine or gem). Organic Cofackers, firmly related to the enzyme, are also called prosthetic groups. Organic Cofackers, capable of separating the enzyme, are called coecments.

An enzyme that requires a cofactor for manifestation of catalytic activity, but is not associated with it, called the apoth enzyme. The apoth enzyme in the complex with the cofactor is called the holo-enzyme. Most of the cofactors are associated with the enzyme with non-covalent, but rather strong interactions. There are such prosthetic groups that are associated with an enzyme covalently, for example, thiaminepyrophosphate in pyruvate dehydrogenase.

Regulation of the enzymes

Some enzymes have small molecules binding sites, they can be substrates or the products of the metabolic path, which enters the enzyme. They reduce or increase the activity of the enzyme, which creates an opportunity for feedback.

Inhibition of finite product

Metabolic pathway - chain of consecutive enzymatic reactions. Often the final product of the metabolic path is an enzyme inhibitor accelerating the first reaction of this metabolic path. If the final product is too much, then it acts as an inhibitor for the very first enzyme, and if after this end product has become too small, then the first enzyme is activated again. Thus, inhibition of the final product according to the principle of negative feedback is an important method of maintaining homeostasis (the relative constancy of the conditions of the inner environment of the body).

Effect of environmental conditions on enzyme activity

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