enzyme

[méi]

Protein or RNA produced by living cells with high specificity and catalytic efficiency for their substrates

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Enzymes（ enzyme ）Is created by Living cell Produced with height to its substrate Specificity And highly catalytic protein or RNA 。 Enzymatic Catalysis Enzyme dependent Primary structure and space structure The integrity of. If the enzyme molecule is denatured or Subunit Disaggregation can lead to enzymatic activity Loss. Enzymes Biomacromolecule The molecular weight is at least 10000, and the larger one can reach one million.

Enzymes are a class of extremely important Biocatalyst （ biocatalyst ）。 Due to the action of enzymes chemical reaction It can also be carried out efficiently and specially under extremely mild conditions.

With people's understanding of enzyme molecules Structure and function 、 Enzymatic reaction kinetics And gradually formed enzymology (ecology).

Enzymatic Chemical essence yes protein （ protein ）Or RNA (Ribonucleic Acid), so it also has primary, secondary, tertiary, and even Four level structure 。 According to the different molecular composition, it can be divided into Simple enzyme and Conjugating enzyme 。 Only containing protein is called pure enzyme; The binding enzyme is composed of Enzyme protein and Cofactor form. For example, most hydrolase It is composed solely of protein; Flavin mononucleotide Enzymes are composed of enzyme proteins and cofactors. The enzyme protein in the binding enzyme is the protein part, and the cofactor is the non protein part. Only when they are combined into a complete enzyme can they have catalytic activity 。

Enzyme is different from common catalyzer The remarkable feature of: enzyme pair substrate Highly specific Catalytic efficiency 。 The enzyme is adjustable and unstable.^[1]

Chinese name: enzyme
Foreign name: enzyme (English)
Enzyme (こそ) (Japanese)
chemical formula: No exact chemical formula
molecular weight: No fixed molecular weight
Application: Medical production

Contains elements: carbon （C）、 hydrogen （H）、 oxygen （O）、 nitrogen （N）、 sulfur （S）
Features: catalysis
Features: High specificity, high catalytic efficiency, adjustability, instability
Chemical essence: Protein or RNA

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Research History

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In 1773, Italian scientist Lazzaro Spallanzani (L. Spallanzani, 1729-1799) designed an ingenious experiment: put meat into a small metal cage and let the eagle swallow it. After a while, he will Xiaolong Take it out and find that the meat has disappeared.

In 1833, Payen and Persoz from France malt The hydrolysate of starch is precipitated with alcohol to obtain a substance that can hydrolyze starch into sugar and is named diastase, which is what we call amylase 。 Later, diastase became the name for all enzymes in France.^[2]

Mapu, Germany, 1836 Institute of Biology scientist Shiwang (T. Schwann, 1810-1882) The substance for digesting protein was extracted from gastric juice to solve the mystery of digestion.

In 1878, Kunne carried out alcohol fermentation Is called "enzyme"（ enzyme ）, this time from Greek , which means "in alcohol".

In 1913, American scientists Michaelis and Menten Intermediate product theory Derive enzyme catalysis basic equation Michaelis equation of.

In 1926, American scientist J.B. Sumner (1887-1955) sword bean The crystal of urease was extracted from the seeds, and it was confirmed by chemical experiments that urease was a protein.

In the 1930s, scientists successively extracted protein crystals of various enzymes, and pointed out that enzymes are a kind of Biocatalysis Active protein.

In 1982, American scientists T.R. Cech (1947 -) and S. Altman (1939-2022) found a few RNA It also has biocatalysis and is named ribozyme 。^[3]

In 1982, American scientist T Cech and his colleagues“ Tetrahymena Encoding rRNA precursors DNA sequence With interval Intron In the study of "sequence", it was found that RNA splicing introns has catalytic function. In order to distinguish it from enzyme, Cech named it ribozyme“ ribozyme ”, on Non coding RNA It is also called "catalytic microRNA" in the classification of.^[4]

In 1986, Schultz and Lerner successfully developed Antibody enzyme （abzyme）。

In 2021, Chinese scientists generated a new enzyme and designed an unnatural 11 step reaction from scratch CO2 fixation And Synthetic starch New approaches. This "creation" only requires water, carbon dioxide and electricity, not relying on photosynthesis , known as "will be a great influence on the world disruptive technologies ”。^[6]

Physical and chemical properties

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form

According to the chemical composition of the enzyme, the enzyme can be divided into Simple enzyme and Conjugating enzyme Two types. Simple enzyme molecule is an enzyme with only amino acid component after hydrolysis. Binding enzyme molecules are composed of protein and non protein parts, such as metal ions, iron porphyrins or B vitamins Small molecule organic compound 。 The protein part that binds the enzyme is called Enzyme protein （ apoenzyme ）, the non protein parts are collectively referred to as Cofactor (cofactor), composed of both Holoenzyme （ holoenzyme ）； Only the whole enzyme has catalytic activity. If the two are separated, the enzyme activity disappears. Non protein parts such as Iron porphyrin Or with B vitamins If the compound of covalent bond Connected is called Cofactor (Prosthetic group), which cannot be separated from enzyme protein by dialysis or ultrafiltration; On the contrary, the two connected by non covalent bond are called coenzyme (coenzyme), the two can be separated by the above method. There are two kinds of cofactors. One is metal ions, which are often auxiliary groups and play the role of electron transfer; The other is small molecule organic compounds, mainly involved in transport hydrogen atom , electrons or some chemical groups or transport carriers.

The metal ions in the binding enzyme have many functions. They may be the components of the enzyme active center and participate in the catalytic reaction, so that the necessary groups of the substrate and the enzyme active center form the correct spatial arrangement, which is conducive to the occurrence of the enzymatic reaction; Some may be stabilizing enzyme Molecular conformation Play a role on; Some may be used as a bridge to connect the enzyme with the substrate to form Ternary complex ； Metal ions can also neutralize charges and reduce electrostatic repulsion It is beneficial to the combination of substrate and enzyme. Coenzymes and cofactors act as carriers of hydrogen or some chemical groups in catalytic reactions, and play the role of transferring hydrogen or chemical groups. There are many kinds of enzymes in the body, but Cofactor of enzyme There are not many kinds of enzymes. It is common for several enzymes to use the same metal ions as cofactors. The same situation can also be seen in coenzymes and cofactors, such as Glyceraldehyde 3-phosphate dehydrogenase And lactate dehydrogenase NAD +As coenzyme. The specificity of enzyme catalyzed reaction depends on the part of enzyme protein, and the role of coenzyme and cofactor is to participate in the transport of hydrogen and some special chemical groups in the specific reaction process. For enzymes that need cofactors, cofactors are also part of the active center.

Most of the enzyme protein Amino acid residue It is not in contact with the substrate. The enzyme molecule that can specifically combine with the substrate and catalyze the substrate to become a product has a specific three-dimensional structure The region of Active site 。 Amino acid residues constituting the active center of the enzyme Side chain There are different functional groups, such as - NH2- COOH, - SH, - OH and Imidazolyl They come from enzyme molecules Polypeptide chain Different parts of. Some groups start when combined with the substrate Binding group (binding group), some of which play a role in catalytic reaction Catalytic group (categoric group). However, some groups play a role in both binding and catalysis, so the functional groups of the active site are often collectively referred to as essential groups.

space structure

They form a three-dimensional structure on the surface of enzyme molecules space structure Of Cavity Or fissure, to accommodate the incoming substrate and combine with it and catalyze the substrate to transform into products. This region is called the active center of the enzyme. However, the active center of the enzyme is only a small part of the enzyme molecule. The specificity of enzyme catalytic reaction actually depends on the binding group, catalytic group and its spatial structure of the enzyme active center.

The functional groups outside the active center of the enzyme are also necessary to form and maintain the spatial conformation of the enzyme, so they are called essential groups outside the active center.

Naming method

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There are usually two methods: custom naming and system naming.

Customary naming

It is often based on two principles:

1. The substrate of the enzyme, such as amylase;

2. Type of catalytic reaction, such as dehydrogenase 。

There are also comprehensive names according to the above two principles or other characteristics of enzymes, such as Succinate dehydrogenase 、 alkaline phosphatase wait.

Habitual naming is relatively simple and has been used for a long time, but it lacks systematicness and rationality, resulting in confusion of the names of some enzymes. For example: Enterokinase and Myokinase Literally, it looks like two enzymes with different sources but similar functions. In fact, their Action mode as like as an apple is to an oyster. Another example: copper Thiolase and Acetyl CoA turn acyl The enzyme is actually the same enzyme, but its name is completely different.

In view of the above situation and the increasing number of newly discovered enzymes enzymology New developments, international biochemistry The Enzyme Committee of the Association recommended a systematic enzyme naming scheme and classification method It is decided that each enzyme should have a systematic name and a customary name. At the same time, each enzyme has a fixed number.

System naming

The systematic naming of enzymes is based on the overall reaction catalyzed by enzymes.

For example, a trypsin numbered "3.4.21.4",

The first number "3" means hydrolase ；

The second number "4" indicates that it is protease hydrolysis Peptide bond ；

The third number "21" indicates that it is Serine protease There is an important serine on the active site Residue ；

The fourth number "4" indicates that it is the fourth enzyme identified in this type.

It is stipulated that the name of each enzyme should clearly indicate the name of the substrate and its catalytic properties. if Enzyme reaction If there are two kinds of substrates reacting in, both of them should be listed and separated by ":".

For example: Glutamic pyruvic transaminase (Customary name) When writing the system name, its two substrates should be“ L-Alanine ”“ α- Ketoglutaric acid ”At the same time, the reaction property it catalyzes is amino , also need to be specified, so its name is "L-alanine: α- Ketoglutaric acid transaminase ”。

Since the system name is generally very long and inconvenient to use, the customary name can be used in the description.

Enzymes (enzymes) are the products of sugar and fruit fermentation, that is“ Fruit Pickles ”Add "low sweetness" Fruit wine ”A mixture of. For example, a kind of green plum full fermented (non soaked) low alcohol fruit wine

Classification

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Human body and mammal The body contains at least 5000 enzymes. They are either dissolved in cytoplasm In, or with various membrane structure They are bound together or located at specific positions of other structures in the cell, and are only activated when needed. These enzymes are collectively called cells Endoenzyme ； In addition, there are some enzymes that are synthesized in cells and secreted out of cells Extracellular enzyme 。

According to reaction nature

According to the different reaction properties catalyzed by enzymes, enzymes are divided into seven categories:

Oxidoreductases （ oxidoreductase ）Promote substrate Redox reaction Enzymes that catalyze redox reactions can be divided into oxidase and reductase Two types.

Transferases (transfers) Some groups (such as acetyl Base, methyl amino 、 phosphoric acid Base, etc.). For example, Methyltransferase 、 Aminotransferase 、 Acetyltransferase , thiotransferase, kinase and Polymerase Etc.

Hydrolases (hydrolases) catalytic substrate generation Hydrolysis reaction Enzymes. For example, amylase 、 protease 、 lipase 、 phosphatase 、 Glycosidase Etc.

Lyases catalyze the reaction of removing a group from the substrate (non hydrolytic) and leaving a double bond or Reverse reaction Enzymes. For example, Dehydratase 、 decarboxylase 、 carbonic anhydrase 、 Aldolase 、 Citrate Synthase Etc. many Lyase Catalytic reverse reaction to form a new Chemical bond And eliminate the double bond of one substrate. Synthases belong to this category.

isomerase Isomerases catalyze various Isomer 、 Geometric isomer Or optical isomers. For example, isomerase, epienzyme Racemase Etc.

Synthetases (ligases) catalyze the synthesis of two molecular substrates into one molecular compound, and coupling yes ATP Enzymes that release energy by cleavage of phosphate bonds. For example, Glutamine synthetase 、 DNA ligase 、 amino acid ： tRNA Ligase And biotin dependent Carboxylase Etc.

Translocases catalyze ions or molecules Transmembrane transport Or enzymes that move within the membrane. Some of them involve ATP hydrolysis The reactive enzymes are classified as hydrolases (EC 3.6.3 -), but hydrolysis is not the main function of these enzymes. Therefore, the Naming Committee recently decided to classify these enzymes into the seventh category.^[5]

According to the unification of enzymes published by the International Biochemical Association Classification principle On the basis of the above seven categories, each category of enzymes can be divided into several subclasses according to the characteristics of the groups or bonds acted on in the substrate; To more accurately indicate the substrate or reactant Each subclass is further divided into several groups (subclasses); Each group contains several enzymes directly.

For example: lactate dehydrogenase (EC1.1.1.27) catalyzes the following reactions:

Lactate dehydrogenase catalyzed reaction

According to chemical composition

Simple protein

Belongs to simplicity protein Enzymes, except for proteins, do not contain other substances, such as urease , protease, amylase, lipase and Ribonuclease etc.

Conjugated protein

Enzymes that bind proteins, in addition to proteins, also bind some pairs of Thermal stability Non protein of Small molecule Substance or metal ion , the former is called de coenzyme , the latter is called Cofactor The complex formed after the combination of coenzyme and cofactor is called Holoenzyme That is, whole enzyme=coenzyme removal+cofactor.^[4]

By existing form

Precursor Zymogen

Some enzymes such as digestive system Various proteases in Formal synthesis And secretion, and then, it is transported to specific parts. When the body needs it Specificity Proteolytic enzyme Its function is transformed into an active enzyme. These are not catalytic activity The precursor of the enzyme is called zymogen（ zymogen ）。 as Pepsinogen （ pepsinogen ）、 Trypsinogen (trypsinogen) and Chymotrypsinogen （ chymotrypsinogen ）Etc. The process of a substance acting on the zymogen to convert it into an active enzyme is called activation of zymogen （zymogen andactivation of zymogen）。 The substance that converts inactive zymogen into active enzyme is called Activator 。 Activin Activation It has certain specificity.

For example, synthetic Chymotrypsinogen 245 Amino acid residue Single composition Peptide chain , there are 5 pairs inside the molecule Disulfide bond The activation process of the zymogen. First by Trypsin Hydrolysis position 15 Arginine And 16 bits isoleucine Residue Inter Peptide bond , activated into p with complete catalytic activity- Chymotrypsin However, at this time, the enzyme molecule is not yet stable, and the two molecules are removed through the self catalysis of p-chymotrypsin Dipeptide To become a well tool with catalytic activity and stable structure α— Chymotrypsin.

Under normal circumstances, most of the plasma Coagulation factor It basically exists in the form of inactive zymogen, only when the tissue or Vascular intima After damage, inactive zymogen can be transformed into active enzyme, thus triggering a series of cascades Enzymatic reaction , resulting in soluble Fibrinogen Transition to stable fibrin POLYMER , snare platelet Forming blood clots.

Zymogen activation It is beneficial to cut off the specific peptide bond in the proenzyme molecule or remove some peptide segments enzymatic activity The activation of the central forming zymogen has important physiological significance. On the one hand, it guarantees synthetase The cells of Physiological conditions And specified parts are activated and play their physiological roles. Such as activation of coagulation factors after tissue or vascular intima damage; Stomach dominates Cell secretion Pepsinogen and secreted by pancreatic cells Chymotrypsinogen Trypsinogen Elastase It is an obvious example to activate the corresponding active enzymes in the stomach and small intestine to promote the digestion of food proteins. The activation of zymogen caused by the breaking of specific peptide bond is widespread in organisms, which is an important way for organisms to regulate enzyme activity. If the activation process of zymogen is abnormal, it will lead to a series of diseases. Hemorrhagic pancreatitis The cause of pancreatic cancer is that the protease is activated before it enters the small intestine, and the activated protease hydrolyzes its own pancreatic cells, leading to pancreatic hemorrhage and swelling.

isozyme

The concept of isozyme: that is, isozyme is a kind of enzyme with the same catalysis chemical reaction , but Enzyme protein Of molecular structure 、 Physical and chemical properties and Immunogenicity A different class of enzymes. They exist in different tissues of the same race or the same individual, even in different tissues and cells of the same organism Organelle Medium. There are dozens of isozymes known so far, such as Hexokinase ， lactate dehydrogenase Etc., in which lactic acid Dehydrogenase, LDH ）The research is clearest. People and Spine Animal tissue In, there are five molecular forms, which catalyze the following same chemical reactions:

Each of the five isozymes consists of four Subunit form. The subunits of LDH can be divided into skeletal muscle type (M type) and myocardial type (H type) amino acid composition Different, the tetramer composed of two subunits in different proportions has five forms of LDH. H four （LDHl）、H three M one （LDH two ）、H two M two （LDH three ）、H one M three （LDH four ）And M four （LDH five ）。

M. The amino acid composition of H subunit is different, which is determined by different genes. The different proportions of M and H subunits in the five LDHs determine their differences in physical and chemical properties. Generally, five kinds of LDH can be separated by electric ice method, LDH one The swimming speed towards the positive pole is the fastest, while LDH five The swimming speed is the slowest, and the others are between the two, followed by LDH two 、LDH three And LDH four 。 The content of LDH in different tissues is different one And LDH two More, while skeletal muscle And LDH in liver five And LDH four Mainly. Difference of LDH isozyme patterns in different tissues and tissue utilization lactic acid Is related to the physiological process. LDH one And LDH two The affinity for lactic acid is large, making lactic acid dehydrogenation Oxidation pyruvic acid It is beneficial for the myocardium to obtain energy from lactic acid oxidation. LDH five And LDH four It has a large affinity for pyruvate and can reduce pyruvate to lactic acid, which is suitable for the physiological process of muscle obtaining energy in anaerobic fermentation. These isozymes are released into the blood when tissue lesions occur Tissue and organ Therefore, the serum isozyme spectrum has changed. So commonly used serum isozymes Spectral analysis To diagnose diseases.

Allosteric enzyme

Allosteric enzyme usually has Four level structure Polybasic Oligomerase , except for Catalysis Of active center Also called catalytic site; There is also allosteric site. The latter is a combination Allosteric agent (allesteric effector), when it is combined with allosteric agent Molecular conformation Will change slightly, affecting the affinity of the catalytic site to the substrate and Catalytic efficiency 。 If allosteric agents combine to increase the affinity between enzyme and substrate or the catalytic efficiency, it is called Allosteric activator (allosteric activator), on the contrary, those that reduce the affinity or catalytic efficiency of enzyme substrate are called Allosteric inhibitor （allosteric inhibitor）。

The role of enzyme activity regulated by allosteric agent is called Allosteric regulation (allosteric regulation). The catalytic site and allosteric site of allosteric enzymes can coexist in different parts of a subunit, but more often they are located in different subunits. Subunit with catalytic site in the latter case Catalytic subunit , and the name of allosteric site Regulatory subunit 。 Most allosteric enzymes are in Metabolic pathway The allosteric agent of allosteric enzyme is usually some physiological small molecule and the substrate of the enzyme or the metabolic pathway Intermediate product Or end products. Therefore, the catalytic activity of allosteric enzymes is regulated by the concentration of intracellular substrates, metabolic intermediates or end products. End product inhibition Allosteric enzyme in this pathway Feedback suppression （feedback inhibition）。 It means that once the intracellular end product increases, it acts as Allosteric inhibitor Inhibit the enzyme at the beginning of the metabolic pathway, and adjust the speed of the metabolic pathway in time to meet the needs of cell physiological functions. Allosteric enzyme in cells Material metabolism Play an important role in the regulation of. So allosteric enzyme is also called Regulatory enzyme （regulatory enzyme）。

Modifying enzyme

Some enzymes in the body have catalytic activity only after modifying the enzyme molecular structure under the action of other enzymes. Such enzymes are called modification enzymes. Among them Covalent modification It is common, such as enzyme protein serine ， threonine Functional group of residue- OH It can be phosphorylated, which is accompanied by covalent bond Therefore, it is called covalent modification. Due to this modification enzyme activity Change the Covalent modification （covalent modification regulation）。 The most common covalent modification in vivo is the phosphorylation and dephosphorylation of enzymes Acetylation And deacetylation Uridine acid Methylation and demethylation. Because of the rapid covalent modification reaction, it has a cascade Amplification effect Therefore, it is also an important way to regulate material metabolism in the body. Such as catalysis Glycogen decomposition Glycogen of the first step reaction phosphorylase There are active and inactive forms, the active one is called phosphorylase a, and the inactive one is called phosphorylase b. The mutual transformation of these two forms is the process of phosphorylation and dephosphorylation of enzyme molecules.

Multienzyme complex And Multienzyme system

Some enzymes in the body polymerize with each other to form a physical combination, which is called multi enzyme complex（ multienzyme complex）。 If the multienzyme complex is disintegrated, the catalytic activity of each enzyme disappears. The number of enzymes involved in the formation of multienzyme complexes varies, such as catalyzing pyruvate Oxidative decarboxylation Reactive Pyruvate Dehydrogenase The multienzyme complex is composed of three enzymes mitochondrion Intermediate catalysis fatty acid β- oxidation The multienzyme complex of C. The first multi enzyme complex Enzyme catalyzed reaction The product of becomes the substrate of the second enzyme action, and this continues until the end product is generated.

Due to the physical combination, the multi enzyme complex is conducive to the rapid progress of this flow process in terms of spatial conformation, which is an improvement for organisms Enzyme catalytic efficiency Is an effective measure.

Various pathways of substance metabolism in the body often involve many enzymes, which complete in turn Reaction process These enzymes are different from the multi enzyme complex and are not related to each other in structure. Therefore, it is called multienzyme system. If participating Glycolysis All 11 enzymes in the cytoplasm constitute a multi enzyme system.

Multifunctional enzyme

In the 21st century, it was found that some enzyme molecules have various catalytic activities, such as Escherichia coli DNA Polymerase I It's a 109kDa Polypeptide chain , with catalysis DNA Chain synthesis, 3 '- 5' Exonuclease And 5 '- 3' exonuclease activity, using Proteolytic enzyme Slight hydrolysis yields two peptide segments, one containing 5 '- 3' exonuclease activity and the other containing two other enzyme activities, indicating that E. coli DNA Polymerase The molecule contains multiple active centers. Mammalian Fatty acid synthase It is composed of two polypeptide chains, each of which contains the catalytic activity of seven enzymes required for fatty acid synthesis. There are many kinds of catalysis in this enzyme molecule Active site The enzyme of is called Multifunctional enzyme （multifunctional enzyme ）Or Tandem enzyme （tandem enzyme）。 Multifunctional enzyme has more advantages than multienzyme complex in molecular structure, because related chemical reactions are carried out on one enzyme molecule, which is more effective than multienzyme complex. This is also Biological evolution Results.

Function

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catalysis

Catalysis

Enzymes are a class Biocatalyst They dominate the metabolism, nutrition and energy conversion And many other catalytic processes, most of which are closely related to life processes Enzyme catalyzed reaction 。

These properties of enzymes make the intracellular Material metabolism The process can be carried out orderly, so that material metabolism and normal physiological functions can adapt to each other. If due to Genetic defect The deficiency of an enzyme or the weakening of enzyme activity caused by other reasons can lead to Enzyme catalysis The abnormal reaction of the substance Metabolic disorder , and even disease, so the relationship between enzyme and medicine is very close.

Enzymes enable the body to obtain Digestion and absorption And maintain all functions of internal organs, including cell repair, anti-inflammatory and detoxification, metabolism Strengthen immunity Generate energy and promote blood circulation. For example, when rice is chewed in the mouth, the longer the chewing time is, the more obvious the sweetness is, because the starch in rice is secreted in the mouth Salivary amylase Under the action of malt dust Because of. Therefore, chewing more when eating can fully mix food and saliva, which is conducive to digestion. In addition, there are Pepsin , trypsin, etc hydrolase 。 The human body ingests from food protein , must be hydrolyzed into amino acid Then, under the action of other enzymes, more than 20 kinds of amino acids needed by the human body are selected to synthesize various proteins needed by the human body in a certain order.

Catalytic mechanism

The catalytic mechanism of enzyme is basically the same as that of common chemical catalysts, which is also the same as that of reactant Synthsis complex compound , by reducing the reactive activation energy To improve chemical reaction At constant temperature, although the energy contained in each reactant molecule in the chemical reaction system varies greatly average value Low, this is the initial state of the reaction.

The reason why the reaction of S (substrate) → P (product) can be carried out is that a considerable part of S molecules have been activated（ transition state ）Molecules, Activation molecule The more, reaction rate The faster. At a specific temperature, the activation energy of the chemical reaction is mole Energy required for all molecules of a substance to become active molecules (kcal).

The function of enzyme (E) is to temporarily combine with S to form a new compound ES, and the activation state (transition state) of ES is much lower than the energy of the reactant activation molecule in the chemical reaction without catalyst. ES reacts again to produce P and release E. E can combine with other S molecules and repeat the cycle. Reduce the activation energy required for the whole reaction, so that more molecules can react in unit time, and the reaction speed can be accelerated. If there is no catalyst, hydrogen peroxide Decomposition into water and oxygen (2H two O two →2H two O+O two ）The required activation energy is 18 per mole Kilocalorie (1 kcal=4.187 joule ）, using catalase Catalyze this Reaction time Only 2 kcal per mole of activation energy is required, and the reaction rate increases by about 10 eleven Times.

Formation of enzyme (E) and substrate (S) Enzyme substrate complex （ES）

Active center of enzyme The first step of enzyme catalysis is the formation of ES complex by directed combination with substrate. The energy for directional binding comes from a variety of energy formed when the functional group of the enzyme active center interacts with the substrate Noncovalent bond , such as Ionic bond , hydrogen bond Dredge key , also includes Van der Waals 。 The energy generated when they combine is called binding energy （binding energy）。 It is not difficult to understand that each enzyme is selective to its own substrate.

If the enzyme only complements with the substrate to generate ES complex, it cannot further promote the entry of the substrate Transitional state , then enzyme catalysis cannot occur. This is because the enzyme and substrate need to form more non covalent bonds between the enzyme and substrate molecules to generate a complex of enzyme and substrate in the transition state, so as to complete the enzyme catalysis. In fact, in the process of generating more non covalent bonds, the substrate molecule changes from the original ground state Change into a transitional state. That is, the substrate molecule becomes an active molecule, which provides conditions for the combined arrangement of groups required for the chemical reaction of the substrate molecule, the generation of transient unstable charges, and other transformations. So the transition state is not a stable chemistry material , different from Reaction process Intermediate products in. As far as the transition state of a molecule is concerned, the probability of its transformation into a product (P) or into a substrate (S) is equal.

When the enzyme and substrate form ES complex and further form a transition state, more binding energy has been released in this process. It is known that this part of binding energy can offset the activation energy required for the activation of some reactant molecules, so that the molecules previously lower than the activation energy threshold become activated molecules, thus accelerating the speed of chemical reaction

Enzymes and general catalysts are Reaction activation energy To speed up the chemical reaction.

The catalytic specificity of the enzyme is shown in its selectivity to the substrate and catalytic reaction There are two aspects of specificity. In addition to individual spontaneous chemical reactions in the body, most of them are catalyzed by specific enzymes. One enzyme can find its own substrate from thousands of reactants, which is enzyme specificity. According to the difference in the specificity of enzyme catalysis, it can be divided into absolute specificity, relative specificity and Stereoisomerism There are three types of specificity. The absolute specificity of an enzyme that catalyzes only one substrate for reaction, such as urease Hydrolysis only urea Break it down into carbon dioxide And ammonia; If an enzyme can catalyze a class of compounds or a class of Chemical bond The reaction is called relative specificity, such as esterase Existing catalysis Triglyceride Hydrolysis can also hydrolyze other ester bonds. Enzymes with stereoisomerism specificity have strict requirements on the stereoconfiguration of substrate molecules, such as L lactate dehydrogenase Catalysis only L-lactic acid dehydrogenation , Yes D-lactic acid No effect.

The catalytic activity of some enzymes can be affected by many factors, such as Allosteric enzyme suffer Allosteric agent Some enzymes are regulated by Covalent modification Adjustment of, hormone And neurohumors Second Messenger Regulate the enzyme activity, and the effect of inducers or inhibitors on cells Endoenzyme Content (change Enzyme synthesis And decomposition speed).

It should be pointed out that the catalytic reaction of one enzyme is often multiple Catalytic mechanism This is an important reason for the high efficiency of enzymatic reaction.

application

disease diagnosis

With the in-depth study and more and more understanding of enzymes Complex enzyme , playing an increasingly significant role in the regulation of diseases. Enzyme activity in normal human body is relatively stable. When some organs and tissues of human body are damaged or disease occurs, some enzymes are released into blood, urine or body fluids. as acute pancreatitis In serum and urine amylase Activity increased significantly; hepatitis And other causes of liver damage, Hepatocyte necrosis Or increased permeability transaminase Release into the blood to increase serum transaminase; myocardial infarction When, Serum lactate dehydrogenase And phosphoric acid creatine kinase Significantly higher. When Organophosphorus pesticide poisoning When, cholinesterase Activity is inhibited, Serum cholinesterase Activity decline; Some hepatobiliary diseases, especially Biliary obstruction The serum r-glutamyltransferase increased. Therefore, the occurrence and development of some diseases can be understood or judged by measuring the enzyme activity in blood, urine or body fluid.

Clinical treatment

Enzyme therapy Has been gradually recognized by people Enzyme preparation It is more and more widely used in clinic. Such as trypsin Chymotrypsin Etc., can catalyze Proteolysis , this principle has been used Surgery Expanding wound, purulent wound purification, chest and abdominal cavity Serous membrane Treatment of adhesion, etc. stay Thrombophlebitis , myocardial infarction Pulmonary infarction as well as Diffuse intravascular coagulation It can be used in the treatment of diseases such as Fibrinolytic enzyme 、 Streptokinase 、 urokinase Etc. to dissolve clot To prevent the formation of thrombus.

some Compound natural enzyme With high unit SOD enzyme as the main formula, it can not only be used for Adjuvant therapy , on tumour Remarkable results have also been achieved in the use of. In addition, it also uses Competitive inhibition of enzymes Principle, synthesize some Chemicals And carry out bacteriostasis, sterilization and anti-tumor treatment. Such as enzyme Invigorate the spleen Tonifying the kidney in Infertility In terms of other issues, it also has better conditioning. and Sulfonamides And many antibiotics It can inhibit some enzymes necessary for bacterial growth, so it has bacteriostasis and Bactericidal action ； many Antineoplastic drugs can Suppressor cell With nucleic acid or protein synthesis Related enzymes, thereby inhibiting Tumor cell The differentiation and proliferation of the tumor to fight the growth of the tumor; Thiouracil can inhibit Iodization Enzymes, thereby affecting thyroxine It can be used for treatment Hyperthyroidism Etc.

Production and life

Used in the brewing industry yeast Bacteria are produced by relevant microorganisms. Enzymes transform starch into alcohol through hydrolysis, oxidation and other processes; Soy sauce vinegar The production of; Use amylase and cellulase The nutritive value of the treated feed is improved; Washing powder By adding enzyme in, the efficiency of washing powder can be improved, and the sweat stains that are not easy to remove can be easily removed

Due to the wide application of enzymes, the extraction and synthesis of enzymes have become an important research topic. At this time, the enzyme can be extracted from the organism, such as Pineapple peel Medium extractable Bromelain 。 However, due to the low content of enzymes in organisms, a large number of enzymes in industry are produced by microbial fermentation. Generally, it is required to select the required strains under suitable conditions to reproduce and obtain a large number of enzyme preparations. In addition, people are studying the artificial synthesis of enzymes. In short, with the improvement of scientific level, the application of enzymes will have very broad prospects.

Main impacts

The relationship between enzymes and some diseases

Enzyme deficiency Most of the resulting diseases are congenital or genetic , such as Albinism Because Tyrosine hydroxylase lack, Broad bean disease Or right Primaquine The reason of lin sensitive patients is the deficiency of glucose-6-phosphate dehydrogenase. Many moderate and toxic diseases are almost caused by the inhibition of some enzymes. As commonly used Organophosphorus pesticide (e.g Trichlorfon 、 dichlorvos 1059 and Dimethoate When poisoned, it is because of their relationship with choline esterase active center Essential group serine On- OH And inactivate the enzyme. Cholinesterase can catalyze acetylcholine Hydrolysis to choline and acetic acid , when cholinesterase is inhibited Inactivation Post acetylcholinergic Hydrolysis Inhibited, causing the accumulation of acetylcholine and a series of poisoning symptoms, such as muscle tremor , Pupil narrowing hyperhidrosis , slow heartbeat, etc. some metal ion Toxicity is caused by metal ions (such as Hg 2+ ）It can be combined with the necessary groups of some enzyme active centers (such as Cysteine Of- SH ）And inactivate the enzyme.

Reaction characteristics

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1 Efficiency: The catalytic efficiency of enzyme is higher than that of inorganic catalyst, which makes the reaction rate faster;

two Specificity : An enzyme can only catalyze one or a class of substrates, for example, protease can only catalyze Proteolysis Polypeptide forming;

3 Diversity: There are many kinds of enzymes, about 4000 kinds of enzymes have been found so far, and the number of enzymes in organisms is far greater than this number;

4 Mildness: It means that chemical reactions catalyzed by enzymes are generally carried out under mild conditions;

5 Activity adjustability: including inhibitor and activator Regulation, feedback inhibition regulation, covalent modification regulation and Allosteric regulation Etc;

6 Variability: Most enzymes are proteins, so they will be exposed to high temperature strong acid , strong alkali, etc;

7 Catalysis of some enzymes Cofactor of

8 Change Chemical reaction rate , it is almost not consumed;

9 only catalyze existing chemical reactions;

10 can speed up the chemical reaction, but the enzyme cannot change the equilibrium point of the chemical reaction, that is to say, the enzyme can promote the forward reaction as well as the reverse reaction in the same proportion, so the role of the enzyme is to shorten the time required to reach the equilibrium, but the equilibrium constant remains unchanged;

Decrease the activation energy and accelerate the chemical reaction rate;

12 Like inorganic catalysts, poisoning also occurs.

Activity index

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Enzyme catalysis The ability of chemical reaction is called enzyme activity (or enzyme activity, active unit). According to the 1961 International Enzymology Conference: 1 unit of enzyme It refers to the conversion of 1 μ The enzyme amount of mol substrate, or 1 μ The enzyme amount of the relevant group of mol.

influence factor

Enzyme activity can be regulated and controlled by many factors, so that organisms can adapt to changes in external conditions and maintain Life activities 。 Without the involvement of enzymes, metabolism is almost impossible to maintain. The activity index of enzyme is in the unit of enzyme activity. It can be seen from the rice equation that the speed of enzymatic reaction is affected by the concentration of enzyme and substrate, as well as temperature, pH activator and inhibitor Impact.

(1) Enzyme concentration

It can be seen from the rice equation and the diagram of the relationship between the enzyme concentration and the rate of enzymatic reaction that the rate of enzymatic reaction is proportional to the concentration of the enzyme molecule. When the concentration of substrate molecule is sufficient, the more enzyme molecules, the faster the substrate conversion speed. But in fact, when the enzyme concentration is very high, the relationship does not remain, and the curve gradually tends to be flat. According to the analysis, this may be caused by the high concentration of substrate with many inhibitors.

(2) Substrate concentration

stay biochemical reaction Medium, if the enzyme concentration is Constant value When the initial concentration of substrate is low, the rate of enzymatic reaction is proportional to the substrate concentration, that is, it increases with the increase of substrate concentration. When all enzymes combine with the substrate Intermediate product After that, even if the substrate concentration is increased, the concentration of intermediates will not increase, and the speed of enzymatic reaction will not increase.

It can also be concluded that under the same substrate concentration, the rate of enzymatic reaction is proportional to the initial concentration of enzyme. The higher the initial concentration of enzyme, the faster the enzymatic reaction.

In actual measurement, even if the enzyme concentration is high enough, with the increase of substrate concentration reaction rate It did not increase or even be inhibited. The reason is that the high concentration of substrate reduces the Effective concentration , reduced the molecule Diffusivity Thus reducing the speed of enzymatic reaction. Excess substrates gather on the enzyme molecules to generate inactive intermediates, which cannot release the enzyme molecules, thus reducing the reaction speed.

Topoisomerase

(3) Temperature

Various enzymes Optimum temperature Within the range, the enzyme activity is the strongest and the speed of enzymatic reaction is the highest. Within the appropriate temperature range, the rate of enzymatic reaction can be increased by 1~2 times for every 10 ℃ increase in temperature. Different organisms Endoenzyme The optimum temperature of is different. For example, Animal tissue The optimum temperature for all kinds of enzymes is 37 ～ 40 ℃; The optimum temperature of various enzymes in microorganisms is 25~60 ℃, but there are exceptions, for example, the optimum temperature of black koji glucoamylase is 62~64 ℃; huge Bacillus , short Lactobacillus 、 Aerobacter Isosomatic Glucose isomerase The optimum temperature of is 80 ℃; Bacillus subtilis Of Liquefying amylase The optimum temperature of is 85 ～ 94 ℃. It can be seen that some enzymes of Bacillus thermal stability Higher. Too high or too low temperature will reduce the catalytic efficiency of the enzyme, that is, reduce the speed of enzymatic reaction.

When the optimum temperature of the enzyme is below 60 ℃, when the temperature reaches 60~80 ℃, most of the enzyme is destroyed and irreversible denaturation ； When the temperature is close to 100 ℃ Catalysis Completely lost. That's why people have a fever When you don't want to eat.

（4）pH

Enzymes in Optimum pH It shows activity within the range. If it is greater than or less than the optimal pH, it will reduce the enzyme activity. It is mainly manifested in two aspects: ① change the charged state of substrate molecules and enzyme molecules, thus affecting the combination of enzyme and substrate; ② Too high or too low pH will affect the stability of the enzyme, thus causing irreversible damage to the enzyme. The closer the pH value of most enzymes in the human body is to 7, the better the catalytic effect. But in the human body Pepsin It is suitable for the environment with pH value of 1~2, Trypsin The optimum pH of is about 8.

(5) Activator

can Activating enzyme The substance of is called enzyme activator.

Activator type:

① Inorganic cation , such as Sodium ion 、 Potassium ion 、 Copper ion 、 calcium ion Etc;

② Inorganic anion , such as Chloride ion , bromine ion, iodine ion sulfate Ions phosphate Ions, etc;

③ Organic compound , such as vitamin C 、 Cysteine 、 Reducibility glutathione Etc. Many enzymes only show catalytic activity Or strengthen its catalytic activity, which is called Activation 。 However, some enzymes are inactive after synthesis. This enzyme is called Zymogen 。 It must be activated by an appropriate activator before it becomes active.

(6) Inhibitors

Substances that can weaken, inhibit or even destroy enzyme activity are called enzyme inhibitors. It can reduce the speed of enzymatic reaction. Enzyme inhibitors include heavy metal ions carbon monoxide 、 hydrogen sulfide 、 Hydrocyanic acid 、 fluoride 、 Iodization acetic acid 、 alkaloid 、 dyestuff , pair- Chloromercuric benzoic acid 、 Diisopropyl fluorophosphoric acid 、 EDTA 、 surface active agent Etc.

The inhibition of enzymatic reaction can be divided into Competitive inhibition and Non competitive inhibition 。 Substances similar to the substrate structure compete with Active center of enzyme This effect is called competitive inhibition. Competitive inhibition is reversibility Inhibition: the inhibition can be finally relieved and the enzyme activity can be restored by increasing the substrate concentration. Substances similar to the substrate structure are called Competitive inhibitor 。 Inhibitors and Enzyme active center After binding to other sites, the substrate can still bind to the active center of the enzyme, but the enzyme does not show activity. This effect is called noncompetitive inhibition. Non competitive inhibition is irreversible, and the increase of substrate concentration cannot relieve the inhibition of enzyme activity. Inhibitors that bind to sites other than the active center of the enzyme are called Non competitive inhibitor 。

Some substances can be used as both inhibitors of one enzyme and activators of another enzyme.

Discipline application

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biology

In organisms, enzymes play a wide range of functions. Signal transduction and cell activity regulation are inseparable from the involvement of enzymes, especially kinases and phosphatases. Enzymes can also produce movement by catalyzing the hydrolysis of ATP on myosin Muscle contraction And can act as Cytoskeleton Some of them are involved in the transport of intracellular substances. Some are located in cell membrane On ATPase As Ion pump participate in Active transportation 。 Some strange functions in organisms also involve enzymes, for example, luciferase can glowworm luminescence. Viruses also contain enzymes or are involved in infecting cells (e.g HIV Integrase and Reverse transcriptase ）, or participate in virus particles from host cell Release of (e.g influenza virus Of Neuraminidase ）。

A very important function of complex enzymes is to participate in the work of the digestive system. Taking protease as the representative, it can convert macromolecule (Starch and protein) degrades into small molecules smaller than 15 microns to facilitate intestinal tract blood capillary Fully absorbed. Starch cannot be directly absorbed by the intestine, while enzymes can hydrolyze starch to maltose or further to glucose Small molecules that can be absorbed by the intestine. Different enzymes break down different food substrates. stay Herbivorous Ruminant There are some bacteria that can produce cellulase in the digestive system of Plant cell wall To provide absorbable nutrients.

In the metabolic pathway, multiple enzymes perform their functions in a specific order: the product of the former enzyme is the substrate of the latter enzyme; After each enzyme catalyzes the reaction, the product is transferred to another enzyme. In some cases, different enzymes can catalyze the same reaction in parallel, thus allowing more complex regulation: for example, one enzyme can continuously catalyze the reaction with lower activity, while another enzyme can catalyze with higher activity after induction. The existence of enzyme determines that the whole metabolism is carried out in the right way; Once there is no enzyme, metabolism can neither follow the required steps nor complete synthesis at a sufficient speed to meet the needs of cells. In fact, metabolic pathways, such as glycolysis, cannot be carried out independently without enzymes. For example, glucose can react directly with ATP to make one or more carbon atom Phosphorylation; In the absence of enzyme catalysis, the reaction proceeds so slowly that it can be ignored; Once hexokinase is added, the phosphorylation reaction of carbon atom at position 6 is greatly accelerated. Although the phosphorylation reaction of other carbon atoms is also slow, it can be found that the vast majority of products are glucose-6-phosphate after a period of time. So each cell can complete the whole reaction network of metabolic pathway through such a set of functional enzymes.

dynamics

Enzyme kinetics It is to study the enzyme binding substrate ability and catalysis reaction rate Science. Researchers react by enzyme analytical method (enzyme assay) to obtain reaction rate data for enzyme kinetic analysis.

In 1902, Victor Hendry put forward the quantitative theory of enzyme kinetics; Later, the theory was confirmed by others and expanded to Michaelis equation 。 Henry's greatest contribution lies in his first proposal that the enzymatic reaction consists of two steps: first, the substrate reversibly binds to the enzyme to form an enzyme substrate complex; Then, the enzyme completes the catalysis of the corresponding chemical reaction and releases the generated product.

The relationship curve between the initial reaction rate of enzyme (expressed as "V") and the substrate concentration (expressed as "[S]"). With the increase of substrate concentration, the reaction rate of enzyme also tends to the maximum reaction rate (expressed as "V max ”）。 Enzymes can catalyze millions of reactions in one second. For example, Whey acid nucleoside The reaction catalyzed by 5-phosphate decarboxylase takes 78 million years to convert half of the substrate into products without enzyme; For the same reaction process, if this decarboxylase is added, the time required is only 25 milliseconds. The rate of enzyme catalysis depends on reaction conditions and substrate concentration. If there are factors in the reaction conditions that can break the protein chain, such as high temperature, extreme pH and high salt concentration, the enzyme activity will be destroyed; However, increasing the substrate concentration in the reaction system will increase the enzyme activity. Under the condition that the enzyme concentration is fixed, the reaction rate catalyzed by the enzyme is accelerated and tends to the maximum reaction rate (V max ）。 The reason for this phenomenon is that when the concentration of the substrate in the reaction system increases, more and more free enzyme molecules combine with the substrate to form an enzyme substrate complex; When all enzyme molecules Active site They are saturated by the substrate, that is, when all enzyme molecules form the enzyme substrate complex, the catalytic reaction rate reaches the maximum. Of course, V max It is not the only kinetic constant of the enzyme, and the substrate concentration required to achieve a certain reaction rate is also an important kinetic index. This dynamic index is Michaelis constant （K m ）, means reaching V max The substrate concentration required for half the reaction rate. For specific substrates, each enzyme has its own characteristic K m Value, indicating the binding strength between substrate and enzyme (K m The lower the value, the stronger the binding, and the higher the affinity). Another important kinetic index is Catalytic constant , defined as the number of substrates catalyzed by an enzyme active site in one second, used to indicate the ability of the enzyme to catalyze specific substrates.

The catalytic efficiency of the enzyme can be measured by the catalytic constant/Michaelis index. This expression is also called specificity constant, which contains the reaction constants of all steps in the catalytic reaction. Since the specificity constant reflects both the affinity and catalytic ability of the enzyme for the substrate, it can be used to compare the catalytic efficiency of different enzymes for specific substrates or the catalytic efficiency of the same enzyme for different substrates.

Each of enzyme and substrate A collision Will cause the substrate to be catalyzed, so the production rate of the product is no longer dominated by the reaction rate, while the molecular Diffusion rate Played a decisive role. This characteristic of enzymes is called "catalytic perfection" or "kinetic perfection". Examples of related enzymes are Triose phosphate isomerase , carbonic anhydrase acetylcholinesterase , catalase Fumarase 、 β- Lactamase and Superoxide dismutase 。

Mie's equation is based on Law of mass action This law is based on the assumptions of free diffusion and thermodynamically driven collisions. However, due to the high concentration of enzyme/substrate/product and phase separation Or one-dimensional/two-dimensional Molecular motion Many biochemical or cellular processes obviously deviate from the assumption of mass action law. In these cases, the fractal Mie equation can be applied.

There are some enzymes whose catalytic product kinetic rate is even higher than the molecular diffusion rate, which cannot be explained by the currently recognized theory. There are many theoretical model Was proposed to explain this kind of phenomenon. In some cases, enzyme can be used to Additional effect To explain that some enzymes can be dipole The electric field is used to capture the substrate and place the substrate in the correct position to the catalytic active site. Another theoretical model introduces the concept of Quantum Theory The tunneling effect of, that is, protons or electrons can pass through the activation Energy barrier (It's like going through a tunnel), but there are still many disputes about the tunneling effect. Reported findings Tryptamine Presence of intermediate protons tunneling effect 。 Therefore, some researchers believe that there is also a tunneling effect in enzyme catalysis, which can directly penetrate Reaction energy barrier Instead of reducing the energy barrier to achieve catalytic effect in the way of the traditional theoretical model. There are relevant experimental reports that Alcohol dehydrogenase There is a tunneling effect in the catalytic reaction of β - lactamase, but whether the tunneling effect is widespread in enzyme catalyzed reactions is still uncertain.

thermodynamics

Like other catalysts, enzymes do not change the equilibrium constant Instead, the reaction rate is accelerated by reducing the activation energy of the reaction. Generally, the reaction is carried out in the presence or absence of enzyme reaction direction It is the same, but the reaction speed of the former is faster. However, it must be pointed out that in the absence of enzyme, the substrate can generate different products through other non catalyzed "free" reactions, because these different products are formed faster.

Enzymes can link two or more reactions, so one thermodynamics The reaction that is more likely to occur on the surface of the reactor will "drive" another reaction that is not thermodynamically likely to occur. For example, cells are often Enzymatic hydrolysis The energy generated will drive other chemical reactions.

Enzymes can catalyze equally Positive reaction And reverse reaction without changing the reaction itself chemical equilibrium 。 For example, carbonic anhydrase can catalyze the following two reciprocal reactions. Which reaction is catalyzed depends on the concentration of reactants.

Of course, if the reaction balance greatly tends to a certain direction, such as the reaction of releasing high energy, and the reverse reaction cannot occur effectively, then the enzyme actually does not catalyze the direction allowed by thermodynamics, but only catalyzes its reverse reaction.

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