Dictionary
any of several complex proteins that are produced by cells and act as catalysts in specific biochemical reactions
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.]] from inappropriately running out of control.]]An enzyme (from Greek language Greek ''énsymo'' (ένζυμο), formed by ''én'' = at or in and ''simo'' = leaven or yeast) is a protein that catalystcatalyzes, or speeds up, a chemical reaction. Enzymes are essential to sustain life because most chemical reactions in cell (biology)biological cells would occur too slowly, or would lead to different products, without enzymes. A malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a severe disease. For example, phenylketonuria is caused by an enzyme malfunction in the enzyme phenylalanine hydroxylase, which catalyses the first step in the degradation of phenylalanine. If this enzyme does not function, the resulting build-up of phenylalanine leads to mental retardation. Like all catalysts, enzymes work by lowering the activation energy of a reaction, thus allowing the reaction to proceed much faster. Enzymes may speed up reactions by a factor of many thousands. An enzyme, like any catalyst, remains unaltered by the completed reaction and can therefore continue to function. Because enzymes, like all catalysts, do not affect the relative energy between the products and reagents, they do not affect equilibrium of a reaction. However, the advantage of enzymes compared to most other catalysts is their sterio-, regio- and chemoselectivity and specificity. Enzyme activity can be affected by other molecules. Inhibitors are molecules that decrease or abolish enzyme activity; activators are molecules that increase the activity. ''Suicide inhibitors'' are inhibitors that incorporate themselves into the enzyme, permanently deactivating it. Inhibitors can be either natural or man-made. Many drugs are enzyme inhibitors. Aspirin, for example, inhibits an enzyme that produces the inflammation messenger prostaglandin, thus suppressing pain and inflammation. Enzymes are also used in everyday products such as washing detergents, where they speed up chemical reactions involved in cleaning the clothes (for example, breaking down starch stains).More than 5,000 enzymes are known. To name different enzymes, one typically uses the ending ''-ase'' with the name of the chemical being transformed (substrate), e.g., lactase is the enzyme that catalyzes the cleavage of lactose.
Etymology and history - ]]The word wiktionary:enzymeenzyme comes from Greek languageGreek: ''"in leaven"''.As early as the late 1700s and early 1800s, the digestion of meat by stomach secretions and the conversion of starch to sugars by plant extracts and saliva were observed.Studying the fermentation of sugar to alcohol by yeast, Louis Pasteur came to the conclusion that this fermentation was catalyzed by "Vitalismferments" in the yeast, which were thought to function only in the presence of living organisms.In 1897, Hans BuchnerHans and Eduard Buchner inadvertently used yeast extracts to ferment sugar, despite the absence of living yeast cells. They were interested in making extracts of yeast cells for medical purposes, and, as one possible way of preserving them, they added large amounts of sucrose to the extract. To their surprise, they found that the sugar was fermented, even though there were no living yeast cells in the mixture. The term "enzyme" was used to describe the substance(s) in yeast extract that brought about the fermentation of sucrose.An example of an enzyme would be amylase
3D-Structure - In enzymes, as with other proteins, function is determined by structure. An enzyme can be:A monomermonomeric protein, i.e., containing only one polypeptide chain, made up of about hundred amino acids or more; oran oligomeric protein consisting of several polypeptide chains, different or identical, that act together as a unit.As with any protein, each monomer is actually produced as a long, linear chain of amino acids, which folds in a particular fashion to produce a three-dimensional product. Individual monomers may then combine via non-covalent interactions to form a multimeric protein. Most enzymes are far larger molecules than the substrates they act on and that only a very small portion of the enzyme, around 10 amino acids, come into direct contact with the substrate(s). This region, where binding of the substrate(s) and then the reaction occurs, is known as the active site of the enzyme. Sometimes enzymes contain additionally other binding sites. Some enzymes have a binding site for a cofactor, which is needed for catalysis. Some enzymes have a binding site that serve regulatory functions, which increase or decrease the enzyme's activity. These typically bind small molecules, often direct or #Metabolic pathwaysindirect products or substrates of the reaction catalyzed. This provides a means for feedback regulation. The amino acid sidechains of an enzyme are either involved in forming the active site or a binding site, or are needed to form the 3D-structure of the protein. Some amino acid sidechains are not needed for function or structure of the enzyme.
Specificity - Enzymes are usually specific as to the reactions they catalyze and the substrate (biochemistry)substrates that are involved in these reactions. Shape and charge complementarity of enzyme and substrate are responsible for this specificity.
"Lock and key" hypothesis - Enzymes are very specific and it was suggested by Emil Fischer in 1890 that this was because the enzyme had a particular shape into which the substrate(s) fit exactly. This is often referred to as "the lock and key" hypothesis. An enzyme combines with its substrate(s) to form a short-lived enzyme-substrate complex.
Induced fit hypothesis - In 1958 Daniel Koshland suggested a modification to the "lock and key" hypothesis. Enzymes are rather flexible structures. The active site of an enzyme could be modified as the substrate interacts with the enzyme. The amino acids sidechains which make up the active site are molded into a precise shape which enables the enzyme to perform its catalytic function. In some cases the substrate molecule changes shape slightly as it enters the active site.A suitable analogy would be that of a hand changing the shape of a glove as the glove is put on.
Modifications - Many enzymes contain not only a protein part but need additionally various modifications. These modifications are made ''posttranslational'', i.e. after the polypeptide chain was synthesized. Additional groups can be synthesized onto the polypeptide chain. E.g. phosphorylation or glycolisation of the enzyme. Another kind of posttranslational modification is the cleavage and splicing of the polypeptide chain. E.g. chymotrypsin, a digestive protease, is produced in inactive form as chymotrypsinogen in the pancreas and transported in this form to the stomach where it is activated. This prevents the enzyme from harmful digestion of the pancreas or other tissue. This type of inactive precursor to an enzyme is known as a zymogen.
Enzyme cofactors - Some enzymes do not need any additional components to exhibit full activities. However, many enzymes are chemically inactive, and they require additional components to become active. An enzyme cofactor is the non-protein component of an enzyme essential for its catalytic activity. There are three types of cofactors, namely activators, coenzymes, prosthetic groups.
Activators - Certain enzymes require inorganic ions as cofactors. These inorganic ions are called activators. They are mainly metallic monovalent or divalent cations which are either loosely or firmly bound to the enzymes. For example in coagulationblood clotting, calcium ions, known as factor IV, are required to activate thrombokinase to convert prothrombin into thrombin.
Prosthetic groups - .]]Non-protein organic cofactors which are firmly bound to the enzyme molecules are called prosthetic groups. They combine to form an integral part in performing catalytic functions. FAD, a coenzyme containing heavy metals has a similar function as NAD and NADP in carrying hydrogen. Heme is a prosthetic group responsible for carrying electrons in the cytochrome system.
Coenzymes - The cofactors of some other enzymes are non-protein organic molecules known as coenzymes, which are not bonded to enzyme molecules like prosthetic groups. Being vitamin-derivatives, they usually serve as carriers to transfer atoms or functional groups from one enzyme to a substrate. Common examples are Nicotinamide adenine dinucleotideNAD (derived from nicotinic acid, a member of vitamin B complex) and NADP, which act as hydrogen carriers and Coenzyme A that transfers the acetyl groups.Those inactive protein parts of enzymes are called apoenzymes. An apoenzyme works effectively only in the presence of non-protein cofactors. An apoenzyme together with its cofactor constitutes a holoenzyme, i.e., an active enzyme. Most of the cofactors are either regenerated or chemically unchanged at the end of the reactions.
Allosteric modulation - Allosteric enzymes have either effector binding sites, or multiple protein subunits that interact with each other and thus influence catalytic activity. Oh my word
Kinetics - In 1913, Leonor Michaelis and Maud Menten proposed a quantitative theory of enzyme kinetics which is still widely used today (usually referred to as Michaelis-Menten kinetics). Enzymes can perform up to several million catalytic reactions per second; to determine the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is achieved. This is the maximum velocity !(''V''maxmaxM ),? which is the substrate concentration required for an enzyme to reach one half its maximum velocity. Each enzyme has a characteristic ''K''M for a given substrate. Since !''V''maxM and !''V''maxcatmcatmaxcatmcatm8 to 109 (l mol-1 s-1). At this point, every collision of the enzyme with its substrate will result in catalysis and the rate of product formation is not limited by the reaction rate but by the diffusion rate. Enzymes that reach this !''k''catm triose-phosphate isomerase, carbonic anhydrase, acetylcholinesterase, catalase, fumarase, ß-lactamase, and superoxide dismutase.
Thermodynamics - As with all catalysts, all reactions catalyzed by enzymes must be "spontaneous" (containing a net negative Gibbs free energy). With the enzyme, they run in the same direction as they would without the enzyme, just more quickly. However, the uncatalyzed, "spontaneous" reaction might lead to different products than the catalyzed reaction. Furthermore, enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive" a thermodynamically unfavorable one. For example, the cleavage of the high-energy compound Adenosine triphosphateATP is often used to drive other, energetically unfavorable chemical reactions.Many reactions catalyzed by an enzyme are reversible.: Enzymes catalyze the forward and backward reactions equally. They do not alter the equilibrium itself, but only the speed at which it is reached, for example, carbonic anhydrase which catalyzes a reaction in either direction depending on the conditions at the time.: (in Biological tissuetissues - high CO2 concentration): (in lungs - low CO2 concentration)
Inhibition - Enzymes reaction rates can be changed by competitive inhibition, non-competitive inhibition, uncompetitive inhibition and mixed inhibition.
Competitive inhibition - The inhibitor may bind to the substrate binding site as shown in the figure above, thus preventing substrate binding. An example for competitive inhibition is the enzyme succinate dehydrogenase by malonate. Succinate dehydrogenase catalyses the oxidation of succinate to fumarate. (bottom).]]
Uncompetitive inhibition - Uncompetitive inhibition occurs when the inhibitor binds only to the enzyme-substrate complex, not to the free enzyme, the enzyme-inhibitor-substrate (EIS) complex is catalytically inactive. This mode of inhibition is rare.
Non-competitive inhibition - Non-competitive inhibitors never bind to the active center, but to other parts of the enzyme that can be far away from the substrate binding site, consequently, there is no competition between the substrate and inhibitor for the enzyme. The extent of inhibition depends entirely on the inhibitor concentration and will not be affected by the substrate concentration. However, these inhibitors bind only loosely with the enzyme and can be removed to resume the enzymatic activities. For example, cyanide combines with the copper prosthetic groups of the enzyme cytochrome c oxidase, thus inhibiting respiration.By changing the Chemical conformationconformation (the three-dimensional structure) of the enzyme, the inhibitors either disable the ability of the enzyme to bind or turn over its substrate. The EI and EIS-complex have no catalytic activity.
Partially competitive inhibition - The mechanism of partially competitive is similar to that of non-competitive inhibition, except that the EIS-complex has catalytic activity, which may be lower or even higher (partially competitive activation) than that of the ES-complex.
Irreversible inhibitors - Some inhibitor bind irreversibly with the enzyme molecules, inhibiting the catalytic activities permanently. The enzymatic reactions will stop sooner or later and are not affected by an increase in substrate concentration. These are irreversible inhibitors. Examples are heavy metal ions including silver (element)silver, mercury (element)mercury and lead (element)lead ions.Another example of irreversible inhibition is provided by the nerve gas diisopropylfluorophosphate (DFP) designed for use in warfare. It combines with the amino acid serine (contains the —SH group) at the active site of the enzyme acetylcholinesterase. The enzyme deactivates the neurotransmitter acetylcholine. Neurotransmitters are needed to continue the passage of nerve impulses from one neuron to another across the synapse. Once the impulse has been transmitted, acetylcholinesterase functions to deactivate the acetycholine almost immediately by breaking it down. If the enzyme is inhibited, acetylcholine accumulates and nerve impulses cannot be stopped, causing prolonged muscle contraction. Paralysis occurs and death may result since the diaphragmrespiratory muscles are affected. Some insecticides currently in use, including those known as organophosphates (e.g. parathion), have a similar effect on insects, and can also cause harm to nervous systemnervous and muscular system of humans who are overexposed to them.
Metabolic pathways and allosteric enzymes - Several enzymes can work together in a specific order, creating metabolic pathways. In a metabolic pathway, one enzyme takes the product of another enzyme as a substrate. After the catalytic reaction, the product is then passed on to another enzyme. The end product(s) of such a pathway are often inhibitors for one of the first enzymes of the pathway (usually the first irreversible step, called ''committed step''), thus regulating the amount of end product made by thepathways. Such a regulatory mechanism is called a negative feedbacknegative feedback mechanism, because the amount of the end product produced is regulated by its own concentration. Negative feedback mechanism can effectively adjust the rate of synthesis of intermediate metabolites according to the demands of the cells. This helps with effective allocations of materials and energy economy, and it prevents the excess manufacture of end products. Like other homeostasishomeostatic devices, the control of enzymatic action helps to maintain a stable internal environment in living organisms. Enzymes that are regulated by end-production inhibition are usually allosteric enzymes. An allosteric enzyme molecule has an active site and also an allosteric site. The allosteric site can bind with allosteric effectors that affect the activity of the enzyme molecule. Allosteric effectors include allosteric activators and allosteric inhibitors. The binding with an allosteric activator activates an enzyme molecule because the active site is in the right conformation to bind with substrate molecules. The binding with an allosteric inhibitor inactivates the enzyme molecule because the conformation of the active site is altered. The activation and inhibition of an allosteric enzyme are reversible. , the enzyme of the first reaction in the pathway, is an allosteric enzyme, and CTP, the end product, is an allosteric inhibitor of ATCase.]]
Enzyme naming conventions - By common convention, an enzyme's name consists of a description of what it does, with the word ending in ''-ase''. Examples are alcohol dehydrogenase and DNA polymerase. Kinases are enzymes that transfer phosphate groups. This results in different enzymes with the same function having the same basic name; they are therefore distinguished by other characteristics, such their optimal pH (alkaline phosphatase) or their location (membrane ATPase). Furthermore, the reversibility of chemical reactions means that the normal physiological direction of an enzyme's function may not be that observed under laboratory conditions. This can result in the same enzyme being identified with two different names: one stemming from the formal laboratory identification as described above, the other representing its behavior in the cell. For instance the enzyme formally known as ''xylitol:NAD+ 2-oxidoreductase (D-xylulose-forming)'' is more commonly referred to in the cellular physiological sense as ''D-xylulose reductase'', reflecting the fact that the function of the enzyme in the cell is actually the reverse of what is often seen under ''in vitro'' conditions.The iubmb.unibe.ch - International Union of Biochemistry and Molecular Biology has developed a nomenclature for enzymes, the EC numbers; each enzyme is described by a sequence of four numbers, preceded by "EC". The first number broadly classifies the enzyme based on its mechanism: - Glucose isomerase Converts glucose in fructose (high fructose syrups derived from starchy materials have enhanced sweetening properties and lower caloriecalorific values)- Immobilised enzymes Production of high fructose syrupsNote: Although this process is widely used in the USA and Japan, legislation in the EEC restricts its use to protect sugar beet farmers.- RubberRubber industry Catalase To generate oxygen from peroxide to convert latex to foam rubber- PaperPaper industry Amylases Degrade starch to lower viscosity product needed for sizing and coating paper - PhotographyPhotographic industry Protease (ficin) Dissolve gelatin off the scrap Photographic filmfilm allowing recovery of silver present-}
See also - List of enzymes Enzyme Kinetics
References - Koshland D. The Enzymes, v. I, ch. 7, Acad. Press, New York, 1959 Perutz M. Proc. Roy. Soc., B 167, 448, 1967 M.V. Volkenshtein, R.R. Dogonadze, A.K. Madumarov, Z.D. Urushadze, Yu.I. Kharkats. Theory of Enzyme Catalysis.- ''Molekuliarnaya Biologia'', Moscow, 6, 1972, pp. 431-439 (In Russian, English summary) M.V. Volkenshtein, R.R. Dogonadze, A.K. Madumarov, Z.D. Urushadze, Yu.I. Kharkats. Electronic and Conformational Interactions in Enzyme Catalysis.- In: E.L. Andronikashvili (Ed.), ''Konformatsionnie Izmenenia Biopolimerov v Rastvorakh'', Publishing House "Nauka", Moscow, 1973, pp. 153-157 (In Russian, English summary) R.R. Dogonadze, Z.D. Urushadze, V.K. Khidureli. Calculation of Kinetic Parameters of Reactions with the Conformational Transformations.- In: E.L. Andronikashvili (Ed.), ''Konformatsionnie Izmenenia Biopolimerov v Rastvorakh'', Publishing House "Metsniereba", Tbilisi, 1975, pp. 368-375 (In Russian)
External links - commonsCategory:Enzymes us.expasy.org - ExPASy enzyme database, links to Swiss-Prot sequence data, entries in other databases and to related literature searches biochem.ucl.ac.uk - PDBsum links to the known 3-D structure data of enzymes in the Protein Data Bank brenda.uni-koeln.de - BRENDA, comprehensive compilation of information and literature references about all known enzymes; requires payment by commercial users !bioinformatics.weizmann.ac.il< /a> - Weizmann Institute's Genecards Database, extensive database of protein properties and their associated genes. drnelson.utmem.edu - Cytochrome P450 enzymes site lists over 4000 versions of enzymes from this cytochrome in plants and !animalsCategory:EnzymesCategor y:BiochemistryCategory:Metabol ismLink? FAbg !bg:Ензимcs:Enzymda:Enzymd e:Enzymes:Enzimaeo:Enzimofa:ز یمایهfr:Enzymeko:효소io :Enzimoid:Enzimit:Enzimahe:א זיםlt:Fermentasmk:Ензи мms:Enzimnl:Enzymja:酵素pl: Enzympt:Enzimaru:Фермен ыsimple:Enzymesl:Encimsr:Е зимsu:Énzimfi:Entsyymisv: Enzymtr:Enzimzh:酶
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