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Enzyme

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<p>정의<strong>Enzymes</strong> are proteins that catalyze (<em>i.e.</em> accelerate) chemical reactions.<sup class="reference" id="_ref-0">[1]</sup> In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, the products. Almost all processes in a biological cell need enzymes in order to occur at significant rates. Since enzymes are extremely selective for their substrates and speed up only a few reactions from among many possibilities, the set of enzymes made in a cell determines which metabolic pathways occur in that cell.</p><p>Like all catalysts, enzymes work by lowering the activation energy (<em>E</em><sub>a</sub> or Δ<em>G</em><sup>&Dagger;</sup>) for a reaction, thus dramatically accelerating the rate of the reaction. Most enzyme reaction rates are millions of times faster than those of comparable uncatalyzed reactions. As with all catalysts, enzymes are not consumed by the reactions they catalyze, nor do they alter the equilibrium of these reactions. However, enzymes do differ from most other catalysts by being much more specific. Enzymes are known to catalyze about 4,000 biochemical reactions.<sup class="reference" id="_ref-1">[2]</sup> Although almost all enzymes are proteins, not all biochemical catalysts are enzymes, since some RNA molecules called ribozymes also catalyze reactions.<sup class="reference" id="_ref-2">[3]</sup> Synthetic molecules called artificial enzymes also display enzyme-like catalysis.<sup class="reference" id="_ref-3">[4]</sup></p><p>Enzyme activity can be affected by other molecules. Inhibitors are molecules that decrease enzyme activity; activators are molecules that increase activity. Many drugs and poisons are enzyme inhibitors. Activity is also affected by temperature, chemical environment (e.g. pH), and the concentration of substrate. Some enzymes are used commercially, for example, in the synthesis of antibiotics. In addition, some household products use enzymes to speed up biochemical reactions (<em>e.g.</em>, enzymes in biological washing powders break down protein or fat stains on clothes; enzymes in meat tenderizers break down proteins, making the meat easier to chew).</p><p><script type="text/javascript">//<![CDATA[ if (window.showTocToggle) { var tocShowText = "show"; var tocHideText = "hide"; showTocToggle(); } //]]></script></p><p> </p><h2><span class="mw-headline">Etymology and history</span></h2><div class="thumb tright"><div class="thumbinner" style="WIDTH: 182px"><img class="thumbimage" height="252" alt="Eduard Buchner" src="http://upload.wikimedia.org/wikipedia/commons/thumb/b/b2/Eduardbuchner.jpg/180px-Eduardbuchner.jpg" width="180" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>Eduard Buchner</div></div></div><p>As early as the late 1700s and early 1800s, the digestion of meat by stomach secretions<sup class="reference" id="_ref-Reaumur1752_0">[5]</sup> and the conversion of starch to sugars by plant extracts and saliva were known. However, the mechanism by which this occurred had not been identified.<sup class="reference" id="_ref-4">[6]</sup></p><p>In the 19th century, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur came to the conclusion that this fermentation was catalyzed by a vital force contained within the yeast cells called "ferments", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells."<sup class="reference" id="_ref-5">[7]</sup></p><p>In 1878 German physiologist Wilhelm Kühne (1837–1900) first used the term <em>enzyme</em>, which comes from Greek <em>ενζυμον</em> "in leaven", to describe this process. The word <em>enzyme</em> was used later to refer to nonliving substances such as pepsin, and the word <em>ferment</em> used to refer to chemical activity produced by living organisms.</p><p>In 1897 Eduard Buchner began to study the ability of yeast extracts that lacked any living yeast cells to ferment sugar. In a series of experiments at the University of Berlin, he found that the sugar was fermented even when there were no living yeast cells in the mixture.<sup class="reference" id="_ref-6">[8]</sup> He named the enzyme that brought about the fermentation of sucrose "zymase".<sup class="reference" id="_ref-7">[9]</sup> In 1907 he received the Nobel Prize in Chemistry "for his biochemical research and his discovery of cell-free fermentation". Following Buchner's example; enzymes are usually named according to the reaction they carry out. Typically the suffix <em>-ase</em> is added to the name of the substrate (<em>e.g.</em>, lactase is the enzyme that cleaves lactose) or the type of reaction (<em>e.g.</em>, DNA polymerase forms DNA polymers).</p><p>Having shown that enzymes could function outside a living cell, the next step was to determine their biochemical nature. Many early workers noted that enzymatic activity was associated with proteins, but several scientists (such as Nobel laureate Richard Willstätter) argued that proteins were merely carriers for the true enzymes and that proteins <em>per se</em> were incapable of catalysis. However, in 1926, James B. Sumner showed that the enzyme urease was a pure protein and crystallized it; Sumner did likewise for the enzyme catalase in 1937. The conclusion that pure proteins can be enzymes was definitively proved by Northrop and Stanley, who worked on the digestive enzymes pepsin (1930), trypsin and chymotrypsin. These three scientists were awarded the 1946 Nobel Prize in Chemistry.<sup class="reference" id="_ref-8">[10]</sup></p><p>This discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This was first done for lysozyme, an enzyme found in tears, saliva and egg whites that digests the coating of some bacteria; the structure was solved by a group led by David Chilton Phillips and published in 1965.<sup class="reference" id="_ref-9">[11]</sup> This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail.</p><p> </p><h2><span class="mw-headline">Structures and mechanisms</span></h2><dl><dd></dd></dl><div class="thumb tright"><div class="thumbinner" style="WIDTH: 302px"><img class="thumbimage" height="274" alt="Ribbon-diagram showing carbonic anhydrase II. The grey sphere is the zinc cofactor in the active site. Diagram drawn from PDB 1MOO." src="http://upload.wikimedia.org/wikipedia/commons/thumb/4/40/Carbonic_anhydrase.png/300px-Carbonic_anhydrase.png" width="300" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>Ribbon-diagram showing carbonic anhydrase II. The grey sphere is the zinc cofactor in the active site. Diagram drawn from PDB 1MOO.</div></div></div><p>Enzymes are generally globular proteins and range from just 62 amino acid residues in size, for the monomer of 4-oxalocrotonate tautomerase,<sup class="reference" id="_ref-10">[12]</sup> to over 2,500 residues in the animal fatty acid synthase.<sup class="reference" id="_ref-11">[13]</sup> A small number of RNA-based biological catalysts exist, with the most common being the ribosome, these are either referred to as <em>RNA-enzymes</em>, or ribozymes. The activities of enzymes are determined by their three-dimensional structure.<sup class="reference" id="_ref-12">[14]</sup> Most enzymes are much larger than the substrates they act on, and only a small portion of the enzyme (around 3–4 amino acids) is directly involved in catalysis.<sup class="reference" id="_ref-13">[15]</sup> The region that contains these catalytic residues, binds the substrate, and then carries out the reaction is known as the active site. Enzymes can also contain sites that bind cofactors, which are needed for catalysis. Some enzymes also have binding sites for small molecules, which are often direct or indirect products or substrates of the reaction catalyzed. This binding can serve to increase or decrease the enzyme's activity, providing a means for feedback regulation.</p><p>Like all proteins, enzymes are made as long, linear chains of amino acids that fold to produce a three-dimensional product. Each unique amino acid sequence produces a specific structure, which has unique properties. Individual protein chains may sometimes group together to form a protein complex. Most enzymes can be denatured—that is, unfolded and inactivated—by heating, which destroys the three-dimensional structure of the protein. Depending on the enzyme, denaturation may be reversible or irreversible.</p><p> </p><h3><span class="mw-headline">Specificity</span></h3><p>Enzymes are usually very specific as to which reactions they catalyze and the substrates that are involved in these reactions. Complementary shape, charge and hydrophilic/hydrophobic characteristics of enzymes and substrates are responsible for this specificity. Enzymes can also show impressive levels of stereospecificity, regioselectivity and chemoselectivity.<sup class="reference" id="_ref-14">[16]</sup></p><p>Some of the enzymes showing the highest specificity and accuracy are involved in the copying and expression of the genome. These enzymes have "proof-reading" mechanisms. Here, an enzyme such as DNA polymerase catalyses a reaction in a first step and then checks that the product is correct in a second step.<sup class="reference" id="_ref-15">[17]</sup> This two-step process results in average error rates of less than 1 error in 100 million reactions in high-fidelity mammalian polymerases.<sup class="reference" id="_ref-16">[18]</sup> Similar proofreading mechanisms are also found in RNA polymerase,<sup class="reference" id="_ref-17">[19]</sup> aminoacyl tRNA synthetases<sup class="reference" id="_ref-18">[20]</sup> and ribosomes.<sup class="reference" id="_ref-19">[21]</sup></p><p>Some enzymes that produce secondary metabolites are described as promiscuous, as they can act on a relatively broad range of different substrates. It has been suggested that this broad substrate specificity is important for the evolution of new biosynthetic pathways.<sup class="reference" id="_ref-20">[22]</sup></p><p> </p><h4><span class="mw-headline">"Lock and key" model</span></h4><p>Enzymes are very specific, and it was suggested by Emil Fischer in 1894 that this was because both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another.<sup class="reference" id="_ref-21">[23]</sup> This is often referred to as "the lock and key" model. However, while this model explains enzyme specificity, it fails to explain the stabilization of the transition state that enzymes achieve. The "lock and key" model has proven inaccurate and the induced fit model is the most currently accepted enzyme-substrate-coenzyme figure.</p><p> </p><h4><span class="mw-headline">Induced fit model</span></h4><div class="thumb tright"><div class="thumbinner" style="WIDTH: 452px"><img class="thumbimage" height="176" alt="Diagrams to show the induced fit hypothesis of enzyme action." src="http://upload.wikimedia.org/wikipedia/commons/thumb/2/24/Induced_fit_diagram.svg/450px-Induced_fit_diagram.svg.png" width="450" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>Diagrams to show the induced fit hypothesis of enzyme action.</div></div></div><p>In 1958 Daniel Koshland suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continually reshaped by interactions with the substrate as the substrate interacts with the enzyme.<sup class="reference" id="_ref-22">[24]</sup> As a result, the substrate does not simply bind to a rigid active site, the amino acid side chains which make up the active site are moulded into the precise positions that enable the enzyme to perform its catalytic function. In some cases, such as glycosidases, the substrate molecule also changes shape slightly as it enters the active site.<sup class="reference" id="_ref-23">[25]</sup> The active site continues to change until the substrate is completely bound, at which point the final shape and charge is determined.<sup class="reference" id="_ref-24">[26]</sup></p><p> </p><h3><span class="mw-headline">Mechanisms</span></h3><p>Enzymes can act in several ways, all of which lower ΔG<sup>&Dagger;</sup>:<sup class="reference" id="_ref-25">[27]</sup></p>

<ul>

<li>~~유기체가 화학적 반응을 할 때 촉매 작용을 하는 살아 있는 세포에서 생성되는 복합물~~Lowering the activation energy by creating an environment in which the transition state is stabilized (e.g. straining the shape of a substrate - by binding the transition-state conformation of the substrate/product molecules, the enzyme distorts the bound substrate(s) into their transition state form, thereby reducing the amount of energy required to complete the transition). </li> <li>Lowering the energy of the transition state, but without distorting the substrate, by creating an environment with the opposite charge distribution to that of the transition state. </li> <li>Providing an alternative pathway. For example,temporarily reacting with the substrate to form an intermediate ES complex, which would be impossible in the absence of the enzyme. </li> <li>Reducing the reaction entropy change by bringing substrates together in the correct orientation to react. Considering ΔH<sup>&Dagger;</sup> alone overlooks this effect. </li></ul><p>Interestingly, this entropic effect involves destabilization of the ground state,<sup class="reference" id="_ref-26">[28]</sup> and its contribution to catalysis is relatively small.<sup class="reference" id="_ref-27">[29]</sup></p><p> </p><h4><span class="mw-headline">Transition State Stabilization</span></h4><p>The understanding of the origin of the reduction of ΔG<sup>&Dagger;</sup> requires one to find out how the enzymes can stabilize its transition state more than the transition state of the uncatalyzed reaction. Apparently, the most effective way for reaching large stabilization is the use of electrostatic effects, in particular, by having a relatively fixed polar environment that is oriented toward the charge distribution of the transition state.<sup class="reference" id="_ref-28">[30]</sup> Such an environment does not exist in the uncatalyzed reaction in water.</p><p> </p><h4><span class="mw-headline">Dynamics and function</span></h4><p>Recent investigations have provided new insights into the connection between internal dynamics of enzymes and their mechanism of catalysis.<sup class="reference" id="_ref-29">[31]</sup><sup class="reference" id="_ref-30">[32]</sup><sup class="reference" id="_ref-31">[33]</sup> An enzyme's internal dynamics are described as the movement of internal parts (<em>e.g.</em> amino acids, a group of amino acids, a loop region, an alpha helix, neighboring beta-sheets or even entire domain) of these biomolecules, which can occur at various time-scales ranging from femtoseconds to seconds. Networks of protein residues throughout an enzyme's structure can contribute to catalysis through dynamic motions.<sup class="reference" id="_ref-32">[34]</sup><sup class="reference" id="_ref-33">[35]</sup><sup class="reference" id="_ref-34">[36]</sup><sup class="reference" id="_ref-35">[37]</sup> Protein motions are vital to many enzymes, but whether small and fast vibrations or larger and slower conformational movements are more important depends on the type of reaction involved. These new insights also have implications in understanding allosteric effects and developing new drugs.</p><p>It should be clarified, however, that the dynamical time-dependent processes are not likely to help to accelerate enzymatic reactions, since such motions randomize and the rate constant is determined by the probability (P) of reaching the transition state, (P = exp {ΔG<sup>&Dagger;</sup>/RT}).<sup class="reference" id="_ref-36">[38]</sup> Furthermore, the reduction of ΔG<sup>&Dagger;</sup> requires having relatively smaller motions (in relation to the corresponding motions in solution reactions) for the transition between the reactant and the product states. Thus, it is not clear that motional or dynamical effects contribute to the catalysis of the chemical step.</p><p> </p><h3><span class="mw-headline">Allosteric modulation</span></h3><p>Allosteric enzymes change their structure in response to binding of effectors. Modulation can be direct, where the effector binds directly to binding sites in the enzyme, or indirect, where the effector binds to other proteins or protein subunits that interact with the allosteric enzyme and thus influence catalytic activity.</p><p> </p><h2><span class="mw-headline">Cofactors and coenzymes</span></h2><dl><dd><div class="noprint relarticle mainarticle"><em>Main articles: Cofactor (biochemistry) and Coenzyme</em></div></dd></dl><p> </p><h3><span class="mw-headline">Cofactors</span></h3><p>Some enzymes do not need any additional components to show full activity. However, others require non-protein molecules called cofactors to be bound for activity.<sup class="reference" id="_ref-37">[39]</sup> Cofactors can be either inorganic (<em>e.g.</em>, metal ions and iron-sulfur clusters) or organic compounds, (e.g., flavin and heme). Organic cofactors can be either prosthetic groups, which are tightly bound to an enzyme, or coenzymes, which are released from the enzyme's active site during the reaction. Coenzymes include NADH, NADPH and adenosine triphosphate. These molecules act to transfer chemical groups between enzymes.<sup class="reference" id="_ref-38">[40]</sup></p><p>An example of an enzyme that contains a cofactor is carbonic anhydrase, and is shown in the ribbon diagram above with a zinc cofactor bound as part of its active site.<sup class="reference" id="_ref-39">[41]</sup> These tightly-bound molecules are usually found in the active site and are involved in catalysis. For example, flavin and heme cofactors are often involved in redox reactions.</p><p>Enzymes that require a cofactor but do not have one bound are called <em>apoenzymes</em>. An apoenzyme together with its cofactor(s) is called a <em>holoenzyme</em> (this is the active form). Most cofactors are not covalently attached to an enzyme, but are very tightly bound. However, organic prosthetic groups can be covalently bound (<em>e.g.</em>, thiamine pyrophosphate in the enzyme pyruvate dehydrogenase).</p><p> </p><h3><span class="mw-headline">Coenzymes</span></h3><div class="thumb tleft"><div class="thumbinner" style="WIDTH: 152px"><img class="thumbimage" height="167" alt="Space-filling model of the coenzyme NADH" src="http://upload.wikimedia.org/wikipedia/commons/thumb/e/ed/NADH-3D-vdW.png/150px-NADH-3D-vdW.png" width="150" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>Space-filling model of the coenzyme NADH</div></div></div><p>Coenzymes are small organic molecules that transport chemical groups from one enzyme to another.<sup class="reference" id="_ref-40">[42]</sup> Some of these chemicals such as riboflavin, thiamine and folic acid are vitamins, this is when these compounds cannot be made in the body and must be acquired from the diet. The chemical groups carried include the hydride ion (H<sup>-</sup>) carried by NAD or NADP<sup>+</sup>, the acetyl group carried by coenzyme A, formyl, methenyl or methyl groups carried by folic acid and the methyl group carried by S-adenosylmethionine.</p><p>Since coenzymes are chemically changed as a consequence of enzyme action, it is useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different enzymes. For example, about 700 enzymes are known to use the coenzyme NADH.<sup class="reference" id="_ref-41">[43]</sup></p><p>Coenzymes are usually regenerated and their concentrations maintained at a steady level inside the cell: for example, NADPH is regenerated through the pentose phosphate pathway and <em>S</em>-adenosylmethionine by methionine adenosyltransferase.</p><p> </p><h2><span class="mw-headline">Thermodynamics</span></h2><dl><dd><div class="noprint relarticle mainarticle"><em>Main articles: Activation energy, Thermodynamic equilibrium, and Chemical equilibrium</em></div></dd></dl><div class="thumb tright"><div class="thumbinner" style="WIDTH: 302px"><img class="thumbimage" height="235" alt="Diagram of a catalytic reaction, showing the energy niveau at each stage of the reaction. The substrates usually need a large amount of energy to reach the transition state, which then decays into the end product. The enzyme stabilizes the transition state, reducing the energy needed to form this species and thus reducing the energy required to form products." src="http://upload.wikimedia.org/wikipedia/commons/thumb/e/e3/Activation2_updated.svg/300px-Activation2_updated.svg.png" width="300" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>Diagram of a catalytic reaction, showing the energy <em>niveau</em> at each stage of the reaction. The substrates usually need a large amount of energy to reach the transition state, which then decays into the end product. The enzyme stabilizes the transition state, reducing the energy needed to form this species and thus reducing the energy required to form products.</div></div></div><p>As all catalysts, enzymes do not alter the position of the chemical equilibrium of the reaction. Usually, in the presence of an enzyme, the reaction runs in the same direction as it would without the enzyme, just more quickly. However, in the absence of the enzyme, other possible uncatalyzed, "spontaneous" reactions might lead to different products, because in those conditions this different product is formed faster.</p><p>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 hydrolysis of ATP is often used to drive other chemical reactions.</p><p>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 catalyzes its reaction in either direction depending on the concentration of its reactants.</p><dl><dd><img class="tex" alt="\mathrm{CO_2 + H_2O{}^\mathrm{\quad Carbonic\ anhydrase}\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\overrightarrow{\qquad\qquad\qquad\qquad}H_2CO_3}" src="http://upload.wikimedia.org/math/c/8/c/c8c255d26e3f46da6bbacb1606142e6f.png" /> (in tissues; high CO<sub>2</sub> concentration) </dd><dd><img class="tex" alt="\mathrm{H_2CO_3{}^\mathrm{\quad Carbonic\ anhydrase}\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\overrightarrow{\qquad\qquad\qquad\qquad}CO_2 + H_2O}" src="http://upload.wikimedia.org/math/7/e/2/7e2012023ac3500d9e061834ffc2074e.png" /> (in lungs; low CO<sub>2</sub> concentration) </dd></dl><p>Nevertheless, if the equilibrium is greatly displaced in one direction, that is, in a very exergonic reaction, the reaction is <em>effectively</em> irreversible. Under these conditions the enzyme will, in fact, only catalyze the reaction in the thermodynamically allowed direction.</p><p> </p><h2><span class="mw-headline">Kinetics</span></h2><dl><dd><div class="noprint relarticle mainarticle"><em>Main article: Enzyme kinetics</em></div></dd></dl><div class="thumb tleft"><div class="thumbinner" style="WIDTH: 302px"><img class="thumbimage" height="117" alt="Mechanism for a single substrate enzyme catalyzed reaction. The enzyme (E) binds a substrate (S) and produces a product (P)." src="http://upload.wikimedia.org/wikipedia/en/thumb/9/96/Simple_mechanism.svg/300px-Simple_mechanism.svg.png" width="300" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>Mechanism for a single substrate enzyme catalyzed reaction. The enzyme (E) binds a substrate (S) and produces a product (P).</div></div></div><p>Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products. The rate data used in kinetic analyses are obtained from enzyme assays.</p><p>In 1902 Victor Henri <sup class="reference" id="_ref-42">[44]</sup> proposed a quantitative theory of enzyme kinetics, but his experimental data were not useful because the significance of the hydrogen ion concentration was not yet appreciated. After Peter Lauritz Sørensen had defined the logarithmic pH-scale and introduced the concept of buffering in 1909<sup class="reference" id="_ref-43">[45]</sup> the German chemist Leonor Michaelis and his Canadian postdoc Maud Leonora Menten repeated Henri's experiments and confirmed his equation which is referred to as Henri-Michaelis-Menten kinetics (sometimes also Michaelis-Menten kinetics).<sup class="reference" id="_ref-44">[46]</sup> Their work was further developed by G. E. Briggs and J. B. S. Haldane, who derived kinetic equations that are still widely used today.<sup class="reference" id="_ref-45">[47]</sup></p><p>The major contribution of Henri was to think of enzyme reactions in two stages. In the first, the substrate binds reversibly to the enzyme, forming the enzyme-substrate complex. This is sometimes called the Michaelis complex. The enzyme then catalyzes the chemical step in the reaction and releases the product.</p><div class="thumb tright"><div class="thumbinner" style="WIDTH: 302px"><img class="thumbimage" height="210" alt="Saturation curve for an enzyme reaction showing the relation between the substrate concentration (S) and rate (v)." src="http://upload.wikimedia.org/wikipedia/commons/thumb/9/99/Michaelis-Menten_saturation_curve_of_an_enzyme_reaction.svg/300px-Michaelis-Menten_saturation_curve_of_an_enzyme_reaction.svg.png" width="300" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>Saturation curve for an enzyme reaction showing the relation between the substrate concentration (S) and rate (<em>v</em>).</div></div></div><p>Enzymes can catalyze up to several million reactions per second. For example, the reaction catalyzed by orotidine 5'-phosphate decarboxylase will consume half of its substrate in 78 million years if no enzyme is present. However, when the decarboxylase is added, the same process takes just 25 milliseconds.<sup class="reference" id="_ref-46">[48]</sup> Enzyme rates depend on solution conditions and substrate concentration. Conditions that denature the protein abolish enzyme activity, such as high temperatures, extremes of pH or high salt concentrations, while raising substrate concentration tends to increase activity. To find the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is seen. This is shown in the saturation curve on the right. Saturation happens because, as substrate concentration increases, more and more of the free enzyme is converted into the substrate-bound ES form. At the maximum velocity (<em>V</em><sub>max</sub>) of the enzyme, all the enzyme active sites are bound to substrate, and the amount of ES complex is the same as the total amount of enzyme. However, <em>V</em><sub>max</sub> is only one kinetic constant of enzymes. The amount of substrate needed to achieve a given rate of reaction is also important. This is given by the Michaelis-Menten constant (<em>K</em><sub>m</sub>), which is the substrate concentration required for an enzyme to reach one-half its maximum velocity. Each enzyme has a characteristic <em>K</em><sub>m</sub> for a given substrate, and this can show how tight the binding of the substrate is to the enzyme. Another useful constant is <em>k</em><sub>cat</sub>, which is the number of substrate molecules handled by one active site per second.</p><p>The efficiency of an enzyme can be expressed in terms of <em>k</em><sub>cat</sub>/<em>K</em><sub>m</sub>. This is also called the specificity constant and incorporates the rate constants for all steps in the reaction. Because the specificity constant reflects both affinity and catalytic ability, it is useful for comparing different enzymes against each other, or the same enzyme with different substrates. The theoretical maximum for the specificity constant is called the diffusion limit and is about 10<sup>8</sup> to 10<sup>9</sup> (M<sup>-1</sup> s<sup>-1</sup>). 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 with this property are called <em>catalytically perfect</em> or <em>kinetically perfect</em>. Example of such enzymes are triose-phosphate isomerase, carbonic anhydrase, acetylcholinesterase, catalase, fumarase, β-lactamase, and superoxide dismutase.</p><p>Michaelis-Menten kinetics relies on the law of mass action, which is derived from the assumptions of free diffusion and thermodynamically-driven random collision. However, many biochemical or cellular processes deviate significantly from these conditions, because of very high concentrations, phase-separation of the enzyme/substrate/product, or one or two-dimensional molecular movement.<sup class="reference" id="_ref-47">[49]</sup> In these situations, a fractal Michaelis-Menten kinetics may be applied.<sup class="reference" id="_ref-48">[50]</sup><sup class="reference" id="_ref-49">[51]</sup><sup class="reference" id="_ref-50">[52]</sup><sup class="reference" id="_ref-51">[53]</sup></p><p>Some enzymes operate with kinetics which are faster than diffusion rates, which would seem to be impossible. Several mechanisms have been invoked to explain this phenomenon. Some proteins are believed to accelerate catalysis by drawing their substrate in and pre-orienting them by using dipolar electric fields. Other models invoke a quantum-mechanical tunneling explanation, whereby a proton or an electron can tunnel through activation barriers, although for proton tunneling this model remains somewhat controversial.<sup class="reference" id="_ref-52">[54]</sup><sup class="reference" id="_ref-53">[55]</sup> Quantum tunneling for protons has been observed in tryptamine.<sup class="reference" id="_ref-54">[56]</sup> This suggests that enzyme catalysis may be more accurately characterized as "through the barrier" rather than the traditional model, which requires substrates to go "over" a lowered energy barrier.</p><p> </p><h2><span class="mw-headline">Inhibition</span></h2><div class="thumb tright"><div class="thumbinner" style="WIDTH: 402px"><img class="thumbimage" height="280" alt="Competitive inhibitors bind reversibly to the enzyme, preventing the binding of substrate. On the other hand, binding of substrate prevents binding of the inhibitor. Substrate and inhibitor compete for the enzyme." src="http://upload.wikimedia.org/wikipedia/commons/thumb/f/fe/Competitive_inhibition.svg/400px-Competitive_inhibition.svg.png" width="400" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>Competitive inhibitors bind reversibly to the enzyme, preventing the binding of substrate. On the other hand, binding of substrate prevents binding of the inhibitor. Substrate and inhibitor compete for the enzyme.</div></div></div><div class="thumb tright"><div class="thumbinner" style="WIDTH: 402px"><img class="thumbimage" height="534" alt="Types of inhibition. This classification was introduced by W.W. Cleland." src="http://upload.wikimedia.org/wikipedia/en/thumb/3/3a/Inhibition.png/400px-Inhibition.png" width="400" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>Types of inhibition. This classification was introduced by W.W. Cleland.<sup class="reference" id="_ref-55">[57]</sup></div></div></div><dl><dd><div class="noprint relarticle mainarticle"><em>Main article: Enzyme inhibitor</em></div></dd></dl><p>Enzyme reaction rates can be decreased by various types of enzyme inhibitors.</p><dl><dt>Competitive inhibition </dt></dl><p>In competitive inhibition, the inhibitor and substrate compete for the enzyme (i.e., they can not bind at the same time). Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, methotrexate is a competitive inhibitor of the enzyme dihydrofolate reductase, which catalyzes the reduction of dihydrofolate to tetrahydrofolate. The similarity between the structures of folic acid and this drug are shown in the figure to the <em>right</em> bottom. Note that binding of the inhibitor need <em>not</em> be to the substrate binding site (as frequently stated), if binding of the inhibitor changes the conformation of the enzyme to prevent substrate binding and <em>vice versa</em>. In competitive inhibition the maximal velocity of the reaction is not changed, but higher substrate concentrations are required to reach a given velocity, increasing the apparent K<sub>m</sub>.</p><dl><dt>Uncompetitive inhibition </dt></dl><p>In uncompetitive inhibition the inhibitor can not bind to the free enzyme, but only to the ES-complex. The EIS-complex thus formed is enzymatically inactive. This type of inhibition is rare, but may occur in multimeric enzymes.</p><dl><dt>Non-competitive inhibition </dt></dl><p>Non-competitive inhibitors can bind to the enzyme at the same time as the substrate, i.e. they <em>never</em> bind to the active site. Both the EI and EIS complexes are enzymatically inactive. Because the inhibitor can not be driven from the enzyme by higher substrate concentration (in contrast to competitive inhibition), the apparent V<sub>max</sub> changes. But because the substrate can still bind to the enzyme, the K<sub>m</sub> stays the same.</p><dl><dt>Mixed inhibition </dt></dl><p>This type of inhibition resembles the non-competitive, except that the EIS-complex has residual enzymatic activity.</p><p>In many organisms inhibitors may act as part of a feedback mechanism. If an enzyme produces too much of one substance in the organism, that substance may act as an inhibitor for the enzyme at the beginning of the pathway that produces it, causing production of the substance to slow down or stop when there is sufficient amount. This is a form of negative feedback. Enzymes which are subject to this form of regulation are often multimeric and have allosteric binding sites for regulatory substances. Their substrate/velocity plots are not hyperbolar, but sigmoidal (S-shaped).</p><div class="thumb tright"><div class="thumbinner" style="WIDTH: 402px"><img class="thumbimage" height="128" alt="The coenzyme folic acid (left) and the anti-cancer drug methotrexate (right) are very similar in structure. As a result, methotrexate is a competitive inhibitor of many enzymes that use folates." src="http://upload.wikimedia.org/wikipedia/en/6/67/Methotrexate_and_folic_acid_compared.png" width="400" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>The coenzyme folic acid (left) and the anti-cancer drug methotrexate (right) are very similar in structure. As a result, methotrexate is a competitive inhibitor of many enzymes that use folates.</div></div></div><p>Irreversible inhibitors react with the enzyme and form a covalent adduct with the protein. The inactivation is irreversible. These compounds include eflornithine a drug used to treat the parasitic disease sleeping sickness.<sup class="reference" id="_ref-Poulin_0">[58]</sup> Penicillin and Aspirin also act in this manner. With these drugs, the compound is bound in the active site and the enzyme then converts the inhibitor into an activated form that reacts irreversibly with one or more amino acid residues.</p><p> </p><h3><span class="mw-headline">Uses of inactivators</span></h3><p>Inhibitors are often used as drugs, but they can also act as poisons. However, the difference between a drug and a poison is usually only a matter of amount, since most drugs are toxic at some level, as Paracelsus wrote, "<em>In all things there is a poison, and there is nothing without a poison.</em>"<sup class="reference" id="_ref-56">[59]</sup> Equally, antibiotics and other anti-infective drugs are just specific poisons that kill a pathogen but not its host.</p><p>An example of an inactivator being used as a drug is aspirin, which inhibits the COX-1 and COX-2 enzymes that produce the inflammation messenger prostaglandin, thus suppressing pain and inflammation. The poison cyanide is an irreversible enzyme inactivator that combines with the copper and iron in the active site of the enzyme cytochrome c oxidase and blocks cellular respiration.<sup class="reference" id="_ref-57">[60]</sup></p><p> </p><h2><span class="mw-headline">Biological function</span></h2><p>Enzymes serve a wide variety of functions inside living organisms. They are indispensable for signal transduction and cell regulation, often via kinases and phosphatases.<sup class="reference" id="_ref-58">[61]</sup> They also generate movement, with myosin hydrolysing ATP to generate muscle contraction and also moving cargo around the cell as part of the cytoskeleton.<sup class="reference" id="_ref-59">[62]</sup> Other ATPases in the cell membrane are ion pumps involved in active transport. Enzymes are also involved in more exotic functions, such as luciferase generating light in fireflies.<sup class="reference" id="_ref-60">[63]</sup> Viruses can also contain enzymes for infecting cells, such as the HIV integrase and reverse transcriptase, or for viral release from cells, like the influenza virus neuraminidase.</p><p>An important function of enzymes is in the digestive systems of animals. Enzymes such as amylases and proteases break down large molecules (starch or proteins, respectively) into smaller ones, so they can be absorbed by the intestines. Starch molecules, for example, are too large to be absorbed from the intestine, but enzymes hydrolyse the starch chains into smaller molecules such as maltose and eventually glucose, which can then be absorbed. Different enzymes digest different food substances. In ruminants which have a herbivorous diets, microorganisms in the gut produce another enzyme, cellulase to break down the cellulose cell walls of plant fiber.<sup class="reference" id="_ref-61">[64]</sup></p><p>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. Sometimes more than one enzyme can catalyse the same reaction in parallel, this can allow more complex regulation: with for example a low constant activity being provided by one enzyme but an inducible high activity from a second enzyme.</p><p>Enzymes determine what steps occur in these pathways. Without enzymes, metabolism would neither progress through the same steps, nor be fast enough to serve the needs of the cell. Indeed, a metabolic pathway such as glycolysis could not exist independently of enzymes. Glucose, for example, can react directly with ATP to become phosphorylated at one or more of its carbons. In the absence of enzymes, this occurs so slowly as to be insignificant. However, if hexokinase is added, these slow reactions continue to take place except that phosphorylation at carbon 6 occurs so rapidly that if the mixture is tested a short time later, glucose-6-phosphate is found to be the only significant product. Consequently, the network of metabolic pathways within each cell depends on the set of functional enzymes that are present.</p><p> </p><h2><span class="mw-headline">Control of activity</span></h2><p>There are five main ways that enzyme activity is controlled in the cell.</p><ol> <li><strong>Enzyme production</strong> (transcription and translation of enzyme genes) can be enhanced or diminished by a cell in response to changes in the cell's environment. This form of gene regulation is called enzyme induction and inhibition. For example, bacteria may become resistant to antibiotics such as penicillin because enzymes called beta-lactamases are induced that hydrolyse the crucial beta-lactam ring within the penicillin molecule. Another example are enzymes in the liver called cytochrome P450 oxidases, which are important in drug metabolism. Induction or inhibition of these enzymes can cause drug interactions. </li> <li>Enzymes can be <strong>compartmentalized</strong>, with different metabolic pathways occurring in different cellular compartments. For example, fatty acids are synthesized by one set of enzymes in the cytosol, endoplasmic reticulum and the Golgi apparatus and used by a different set of enzymes as a source of energy in the mitochondrion, through β-oxidation.<sup class="reference" id="_ref-62">[65]</sup> </li> <li>Enzymes can be regulated by <strong>inhibitors and activators</strong>. For example, the end product(s) of a metabolic pathway are often inhibitors for one of the first enzymes of the pathway (usually the first irreversible step, called <em>committed step</em>), thus regulating the amount of end product made by the pathways. Such a regulatory mechanism is called a negative 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 allocate materials and energy economically, and prevents the manufacture of excess end products. Like other homeostatic devices, the control of enzymatic action helps to maintain a stable internal environment in living organisms. </li> <li>Enzymes can be regulated through <strong>post-translational modification</strong>. This can include phosphorylation, myristoylation and glycosylation. For example, in the response to insulin, the phosphorylation of multiple enzymes, including glycogen synthase, helps control the synthesis or degradation of glycogen and allows the cell to respond to changes in blood sugar.<sup class="reference" id="_ref-63">[66]</sup> Another example of post-translational modification is the cleavage of the polypeptide chain. 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 stops the enzyme from digesting the pancreas or other tissues before it enters the gut. This type of inactive precursor to an enzyme is known as a zymogen. </li> <li>Some enzymes may become <strong>activated when localized to a different environment</strong> (eg. from a reducing (cytoplasm) to an oxidising (periplasm) environment, high pH to low pH etc). For example, hemagglutinin of the influenza virus undergoes a conformational change once it encounters the acidic environment of the host cell vesicle causing its activation.<sup class="reference" id="_ref-64">[67]</sup> </li></ol><p> </p><h2><span class="mw-headline">Involvement in disease</span></h2><div class="thumb tright"><div class="thumbinner" style="WIDTH: 202px"><img class="thumbimage" height="210" alt="Phenylalanine hydroxylase. Created from PDB 1KW0" src="http://upload.wikimedia.org/wikipedia/commons/thumb/9/97/Phenylalanine_hydroxylase_brighter.jpg/200px-Phenylalanine_hydroxylase_brighter.jpg" width="200" border="0" /><div class="thumbcaption"><div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div>Phenylalanine hydroxylase. Created from PDB 1KW0</div></div></div><p>Since the tight control of enzyme activity is essential for homeostasis, any malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a genetic disease. The importance of enzymes is shown by the fact that a lethal illness can be caused by the malfunction of just one type of enzyme out of the thousands of types present in our bodies.</p><p>One example is the most common type of phenylketonuria. A mutation of a single amino acid in the enzyme phenylalanine hydroxylase, which catalyzes the first step in the degradation of phenylalanine, results in build-up of phenylalanine and related products. This can lead to mental retardation if the disease is untreated.<sup class="reference" id="_ref-65">[68]</sup></p><p>Another example is when germline mutations in genes coding for DNA repair enzymes cause hereditary cancer syndromes such as xeroderma pigmentosum. Defects in these enzymes cause cancer since the body is less able to repair mutations in the genome. This causes a slow accumulation of mutations and results in the development of many types of cancer in the sufferer.</p><p> </p><h2><span class="mw-headline">Naming conventions</span></h2><p>An enzyme's name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in <em><strong>-ase</strong></em>. Examples are lactase, alcohol dehydrogenase and DNA polymerase. This may result in different enzymes, called isoenzymes, with the same function having the same basic name. Isoenzymes have a different amino acid sequence and might be distinguished by their optimal pH, kinetic properties or immunologically. Furthermore, the normal physiological reaction an enzyme catalyzes may not be the same as under artificial conditions. This can result in the same enzyme being identified with two different names. <em>E.g.</em> Glucose isomerase, used industrially to convert glucose into the sweetener fructose, is a xylose isomerase <em>in vivo</em>.</p><p>The International Union of Biochemistry and Molecular Biology have developed a nomenclature for enzymes, the <strong>EC numbers</strong>; each enzyme is described by a sequence of four numbers preceded by "EC". The first number broadly classifies the enzyme based on its mechanism:</p><p>The top-level classification is</p><ul> <li>EC 1 <em>Oxidoreductases</em>: catalyze oxidation/reduction reactions </li> <li>EC 2 <em>Transferases</em>: transfer a functional group (<em>e.g.</em> a methyl or phosphate group) </li> <li>EC 3 <em>Hydrolases</em>: catalyze the hydrolysis of various bonds </li> <li>EC 4 <em>Lyases</em>: cleave various bonds by means other than hydrolysis and oxidation </li> <li>EC 5 <em>Isomerases</em>: catalyze isomerization changes within a single molecule </li> <li>EC 6 <em>Ligases</em>: join two molecules with covalent bonds </li></ul><p>The complete nomenclature can be browsed at http://www.chem.qmul.ac.uk/iubmb/enzyme/.</p><p> </p><h2><span class="mw-headline">Industrial applications</span></h2><p>Enzymes are used in the chemical industry and other industrial applications when extremely specific catalysts are required. However, enzymes in general are limited in the number of reactions they have evolved to catalyse and also by their lack of stability in organic solvents and at high temperatures. Consequently, protein engineering is an active area of research and involves attempts to create new enzymes with novel properties, either through rational design or <em>in vitro</em> evolution.<sup class="reference" id="_ref-66">[69]</sup><sup class="reference" id="_ref-67">[70]</sup></p><p><table class="wikitable"> <tbody> <tr> <td align="center" width="24%"><strong>Application</strong></td> <td align="center" width="38%"><strong>Enzymes used</strong></td> <td align="center" width="38%"><strong>Uses</strong></td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid" rowspan="2"><strong>Baking industry</strong> <div class="center"> <div class="thumb tnone"> <div class="thumbinner" style="WIDTH: 182px"><img class="thumbimage" height="73" alt="alpha-amylase catalyzes the release of sugar monomers from starch" src="http://upload.wikimedia.org/wikipedia/commons/thumb/4/45/Amylose.svg/180px-Amylose.svg.png" width="180" border="0" /> <div class="thumbcaption"> <div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div> alpha-amylase catalyzes the release of sugar monomers from starch</div> </div> </div> </div> </td> <td style="BORDER-TOP: #aaaaaa 3px solid">Fungal alpha-amylase enzymes are normally inactivated at about 50 degrees Celsius, but are destroyed during the baking process.</td> <td style="BORDER-TOP: #aaaaaa 3px solid">Catalyze breakdown of starch in the flour to sugar. Yeast action on sugar produces carbon dioxide. Used in production of white bread, buns, and rolls.</td> </tr> <tr> <td>Proteases</td> <td>Biscuit manufacturers use them to lower the protein level of flour.</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid"><strong>Baby foods</strong></td> <td style="BORDER-TOP: #aaaaaa 3px solid">Trypsin</td> <td style="BORDER-TOP: #aaaaaa 3px solid">To predigest baby foods.</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid" rowspan="6"><strong>Brewing industry</strong> <div class="center"> <div class="thumb tnone"> <div class="thumbinner" style="WIDTH: 182px"><img class="thumbimage" height="135" alt="Germinating barley used for malt." src="http://upload.wikimedia.org/wikipedia/commons/thumb/3/32/Sjb_whiskey_malt.jpg/180px-Sjb_whiskey_malt.jpg" width="180" border="0" /> <div class="thumbcaption"> <div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div> Germinating barley used for malt.</div> </div> </div> </div> </td> <td style="BORDER-TOP: #aaaaaa 3px solid">Enzymes from barley are released during the mashing stage of beer production.</td> <td style="BORDER-TOP: #aaaaaa 3px solid">They degrade starch and proteins to produce simple sugar, amino acids and peptides that are used by yeast for fermentation.</td> </tr> <tr> <td>Industrially produced barley enzymes</td> <td>Widely used in the brewing process to substitute for the natural enzymes found in barley.</td> </tr> <tr> <td>Amylase, glucanases, proteases</td> <td>Split polysaccharides and proteins in the malt.</td> </tr> <tr> <td>Betaglucanases and arabinoxylanases</td> <td>Improve the wort and beer filtration characteristics.</td> </tr> <tr> <td>Amyloglucosidase and pullulanases</td> <td>Low-calorie beer and adjustment of fermentability.</td> </tr> <tr> <td>Proteases</td> <td>Remove cloudiness produced during storage of beers.</td> </tr> <tr> <td> </td> <td>Acetolactatedecarboxylase (ALDC)</td> <td>Avoid the formation of diacetyl</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid"><strong>Fruit juices</strong></td> <td style="BORDER-TOP: #aaaaaa 3px solid">Cellulases, pectinases</td> <td style="BORDER-TOP: #aaaaaa 3px solid">Clarify fruit juices</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid" rowspan="4"><strong>Dairy industry</strong> <div class="center"> <div class="thumb tnone"> <div class="thumbinner" style="WIDTH: 182px"><img class="thumbimage" height="144" alt="Roquefort cheese" src="http://upload.wikimedia.org/wikipedia/commons/thumb/9/92/Roquefort_cheese.jpg/180px-Roquefort_cheese.jpg" width="180" border="0" /> <div class="thumbcaption"> <div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div> Roquefort cheese</div> </div> </div> </div> </td> <td style="BORDER-TOP: #aaaaaa 3px solid">Rennin, derived from the stomachs of young ruminant animals (like calves and lambs).</td> <td style="BORDER-TOP: #aaaaaa 3px solid">Manufacture of cheese, used to hydrolyze protein.</td> </tr> <tr> <td>Microbially produced enzyme</td> <td>Now finding increasing use in the dairy industry.</td> </tr> <tr> <td>Lipases</td> <td>Is implemented during the production of Roquefort cheese to enhance the ripening of the blue-mould cheese.</td> </tr> <tr> <td>Lactases</td> <td>Break down lactose to glucose and galactose.</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid"><strong>Meat tenderizers</strong></td> <td style="BORDER-TOP: #aaaaaa 3px solid">Papain</td> <td style="BORDER-TOP: #aaaaaa 3px solid">To soften meat for cooking.</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid" rowspan="2"><strong>Starch industry</strong> <div class="center"> <div class="thumb tnone"> <div class="thumbinner" style="WIDTH: 208px"> <table style="BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; BORDER-LEFT-WIDTH: 0px; BACKGROUND: none transparent scroll repeat 0% 0%; BORDER-BOTTOM-WIDTH: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px; WIDTH: 204px; PADDING-TOP: 0px; BORDER-RIGHT-WIDTH: 0px" cellspacing="0"> <tbody> <tr> <td class="thumbimage" style="PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px; PADDING-TOP: 0px"><img height="97" alt="Glucose" src="http://upload.wikimedia.org/wikipedia/commons/thumb/c/c6/Alpha-D-Glucopyranose.svg/90px-Alpha-D-Glucopyranose.svg.png" width="90" border="0" /></td> <td style="BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px; WIDTH: 2px; PADDING-TOP: 0px; BORDER-RIGHT-WIDTH: 0px"> </td> <td class="thumbimage" style="PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px; PADDING-TOP: 0px"><img height="94" alt="Glucose" src="http://upload.wikimedia.org/wikipedia/commons/thumb/4/4a/Alpha-D-Fructofuranose.svg/110px-Alpha-D-Fructofuranose.svg.png" width="110" border="0" /></td> </tr> <tr> <td style="BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px; PADDING-TOP: 0px; BORDER-RIGHT-WIDTH: 0px"> <div class="thumbcaption">Glucose</div> </td> <td style="BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px; PADDING-TOP: 0px; BORDER-RIGHT-WIDTH: 0px"> </td> <td style="BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px; PADDING-TOP: 0px; BORDER-RIGHT-WIDTH: 0px"> <div class="thumbcaption">Fructose</div> </td> </tr> </tbody> </table> </div> </div> </div> </td> <td style="BORDER-TOP: #aaaaaa 3px solid">Amylases, amyloglucosideases and glucoamylases</td> <td style="BORDER-TOP: #aaaaaa 3px solid">Converts starch into glucose and various syrups.</td> </tr> <tr> <td>Glucose isomerase</td> <td>Converts glucose into fructose in production of high fructose syrups from starchy materials. These syrups have enhanced sweetening properties and lower calorific values than sucrose for the same level of sweetness.</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid"><strong>Paper industry</strong> <div class="center"> <div class="thumb tnone"> <div class="thumbinner" style="WIDTH: 162px"><img class="thumbimage" height="120" alt="A paper mill in South Carolina." src="http://upload.wikimedia.org/wikipedia/commons/thumb/c/c5/InternationalPaper6413.jpg/160px-InternationalPaper6413.jpg" width="160" border="0" /> <div class="thumbcaption"> <div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div> A paper mill in South Carolina.</div> </div> </div> </div> </td> <td style="BORDER-TOP: #aaaaaa 3px solid">Amylases, Xylanases, Cellulases and ligninases</td> <td style="BORDER-TOP: #aaaaaa 3px solid">Degrade starch to lower viscosity, aiding sizing and coating paper. Xylanases reduce bleach required for decolorising; cellulases smooth fibers, enhance water drainage, and promote ink removal; lipases reduce pitch and lignin-degrading enzymes remove lignin to soften paper.</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid" rowspan="2"><strong>Biofuel industry</strong> <div class="center"> <div class="thumb tnone"> <div class="thumbinner" style="WIDTH: 182px"><img class="thumbimage" height="103" alt="Cellulose in 3D" src="http://upload.wikimedia.org/wikipedia/commons/thumb/9/9c/Cellulose-3D-balls.png/180px-Cellulose-3D-balls.png" width="180" border="0" /> <div class="thumbcaption"> <div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div> Cellulose in 3D</div> </div> </div> </div> </td> <td style="BORDER-TOP: #aaaaaa 3px solid">Cellulases</td> <td style="BORDER-TOP: #aaaaaa 3px solid">Used to break down cellulose into sugars that can be fermented (see cellulosic ethanol).</td> </tr> <tr> <td>Ligninases</td> <td>Use of lignin waste</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid" rowspan="4"><strong>Biological detergent</strong> <div class="center"> <div class="thumb tnone"> <div class="thumbinner" style="WIDTH: 182px"><img class="thumbimage" height="135" alt="Laundry soap" src="http://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Washingpowder.jpg/180px-Washingpowder.jpg" width="180" border="0" /> <div class="thumbcaption"> <div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div> Laundry soap</div> </div> </div> </div> </td> <td style="BORDER-TOP: #aaaaaa 3px solid">Primarily proteases, produced in an extracellular form from bacteria</td> <td style="BORDER-TOP: #aaaaaa 3px solid">Used for presoak conditions and direct liquid applications helping with removal of protein stains from clothes.</td> </tr> <tr> <td>Amylases</td> <td>Detergents for machine dish washing to remove resistant starch residues.</td> </tr> <tr> <td>Lipases</td> <td>Used to assist in the removal of fatty and oily stains.</td> </tr> <tr> <td>Cellulases</td> <td>Used in biological fabric conditioners.</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid"><strong>Contact lens cleaners</strong></td> <td style="BORDER-TOP: #aaaaaa 3px solid">Proteases</td> <td style="BORDER-TOP: #aaaaaa 3px solid">To remove proteins on contact lens to prevent infections.</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid"><strong>Rubber industry</strong></td> <td style="BORDER-TOP: #aaaaaa 3px solid">Catalase</td> <td style="BORDER-TOP: #aaaaaa 3px solid">To generate oxygen from peroxide to convert latex into foam rubber.</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid"><strong>Photographic industry</strong></td> <td style="BORDER-TOP: #aaaaaa 3px solid">Protease (ficin)</td> <td style="BORDER-TOP: #aaaaaa 3px solid">Dissolve gelatin off scrap film, allowing recovery of its silver content.</td> </tr> <tr> <td style="BORDER-TOP: #aaaaaa 3px solid"><strong>Molecular biology</strong> <div class="center"> <div class="thumb tnone"> <div class="thumbinner" style="WIDTH: 182px"><img class="thumbimage" height="100" alt="Part of the DNA double helix." src="http://upload.wikimedia.org/wikipedia/commons/thumb/d/d9/DNA123_rotated.png/180px-DNA123_rotated.png" width="180" border="0" /> <div class="thumbcaption"> <div class="magnify" style="FLOAT: right"><img height="11" alt="" src="http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png" width="15" /></div> Part of the DNA double helix.</div> </div> </div> </div> </td> <td style="BORDER-TOP: #aaaaaa 3px solid">Restriction enzymes, DNA ligase and polymerases</td> <td style="BORDER-TOP: #aaaaaa 3px solid">Used to manipulate DNA in genetic engineering, important in pharmacology, agriculture and medicine. Essential for restriction digestion and the polymerase chain reaction. Molecular biology is also important in forensic science.</td> </tr> </tbody></table></p><p> </p><h2><span class="mw-headline">See also</span></h2><ul> <li>List of enzymes </li> <li>Enzyme assay </li> <li>Enzyme catalysis </li> <li>RNA Biocatalysis </li> <li>SUMO enzymes </li> <li>K<sub>i</sub> Database </li> <li>Proteonomics and protein engineering </li></ul><p> </p><h2><span class="mw-headline">References</span></h2><div class="references-small" style="-moz-column-count: 2; -webkit-column-count: 2; column-count: 2"><ol class="references"> <li id="_note-0"><strong>^</strong> Smith AD (Ed) <em>et al.</em> (1997) <em>Oxford Dictionary of Biochemistry and Molecular Biology</em> Oxford University Press ISBN 0-19-854768-4 </li> <li id="_note-1"><strong>^</strong> <cite style="FONT-STYLE: normal">Bairoch A. (2000). "The ENZYME database in 2000". <em>Nucleic Acids Res</em> <strong>28</strong>: 304–305. 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"Rational design of thermally stable proteins: relevance to bionanotechnology.". <em>J Nanosci Nanotechnol.</em> <strong>5</strong> (11): 1759–1767. PMID 16433409.</cite> </li> <li id="_note-67"><strong>^</strong> <cite style="FONT-STYLE: normal">Hult K, Berglund P. (2003). "Engineered enzymes for improved organic synthesis.". <em>Curr Opin Biotechnol.</em> <strong>14</strong> (4): 395–400. PMID 12943848.</cite> </li></ol></div><p> </p><h2><span class="mw-headline">Further reading</span></h2><p><table style="BACKGROUND: none transparent scroll repeat 0% 0%; WIDTH: 100%" cellspacing="0" cellpadding="0" class="multicol"> <tbody> <tr> <td valign="top" align="left" width="50%"> <p><strong>Etymology and history</strong></p> <ul> <li>New Beer in an Old Bottle: Eduard Buchner and the Growth of Biochemical Knowledge, edited by Athel Cornish-Bowden and published by Universitat de València (1997): ISBN 84-370-3328-4, A history of early enzymology. </li> <li>Williams, Henry Smith, 1863–1943. A History of Science: in Five Volumes. Volume IV: Modern Development of the Chemical and Biological Sciences, A textbook from the 19th century. </li> <li>Kleyn, J. and Hough J. The Microbiology of Brewing. <em>Annual Review of Microbiology</em> (1971) Vol. 25: 583–608 </li> </ul> <p><strong>Enzyme structure and mechanism</strong></p> <ul> <li>Fersht, A. Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding. W. H. Freeman, 1998 ISBN 0-7167-3268-8 </li> <li>Walsh, C., Enzymatic Reaction Mechanisms. W. H. Freeman and Company. 1979. ISBN 0-7167-0070-0 </li> <li>Page, M. I., and Williams, A. (Eds.), 1987. Enzyme Mechanisms. Royal Society of Chemistry. ISBN 0-85186-947-5 </li> <li>Bugg, T. Introduction to Enzyme and Coenzyme Chemistry, 2004, Blackwell Publishing Limited; 2nd edition. ISBN 1-40511-452-5 </li> <li>Warshel, A., Computer Modeling of Chemical Reactions in enzymes and Solutions John Wiley & Sons Inc. 1991. ISBN 0-471-18440-3 </li> </ul> <p><strong>Thermodynamics</strong></p> <ul> <li>Reactions and Enzymes Chapter 10 of On-Line Biology Book at Estrella Mountain Community College. </li> </ul> </td> <td valign="top" align="left" width="50%"> <p><strong>Kinetics and inhibition</strong></p> <ul> <li>Athel Cornish-Bowden, <em>Fundamentals of Enzyme Kinetics</em>. (3rd edition), Portland Press (2004), <a class="internal" href="http://en.wikipedia.org/w/index.php?title=Special:Booksources&isbn=1855781581">ISBN 1-85578-158-1</a>. </li> <li>Irwin H. Segel, <em>Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems</em>. Wiley-Interscience; New Ed edition (1993), <a class="internal" href="http://en.wikipedia.org/w/index.php?title=Special:Booksources&isbn=0471303097">ISBN 0-471-30309-7</a>. </li> <li>John W. Baynes, <em>Medical Biochemistry</em>, Elsevier-Mosby; 2th Edition (2005), <a class="internal" href="http://en.wikipedia.org/w/index.php?title=Special:Booksources&isbn=0723433410">ISBN 0-7234-3341-0</a>, p. 57. </li> </ul> <p><strong>Function and control of enzymes in the cell</strong></p> <ul> <li>Price, N. and Stevens, L., Fundamentals of Enzymology: Cell and Molecular Biology of Catalytic Proteins Oxford University Press, (1999), <a class="internal" href="http://en.wikipedia.org/w/index.php?title=Special:Booksources&isbn=019850229X">ISBN 0-19-850229-X</a> </li> <li><a class="external text" title="http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.chapter.86" href="http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.chapter.86" rel="nofollow">Nutritional and Metabolic Diseases</a> Chapter of the on-line textbook "Introduction to Genes and Disease" from the NCBI. </li> </ul> <p><strong>Enzyme-naming conventions</strong></p> <ul> <li><a class="external text" title="http://www.chem.qmul.ac.uk/iubmb/enzyme/" href="http://www.chem.qmul.ac.uk/iubmb/enzyme/" rel="nofollow">Enzyme Nomenclature</a>, Recommendations for enzyme names from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology. </li> <li>Koshland D. The Enzymes, v. I, ch. 7, Acad. Press, New York, (1959) </li> </ul> <p><strong>Industrial applications</strong></p> <ul> <li><a class="external text" title="http://www.mapsenzymes.com/History_of_Enzymes.asp" href="http://www.mapsenzymes.com/History_of_Enzymes.asp" rel="nofollow">History of industrial enzymes</a>, Article about the history of industrial enzymes, from the late 1900s to the present times. </li> </ul> </td> </tr> </tbody></table></p><p><a id="External_links" name="External_links"></a></p><h2><span class="mw-headline">External links</span></h2><div class="infobox sisterproject"><div class="floatleft"><span><a class="image" title="Commons-logo.svg" href="http://en.wikipedia.org/wiki/Image:Commons-logo.svg"></a></span></div><div style="MARGIN-LEFT: 60px"><div style="MARGIN-LEFT: 10px"><em><strong><a class="extiw" title="commons:Category:Enzymes" href="http://commons.wikimedia.org/wiki/Category:Enzymes"></a></strong></em></div></div></div><ul> <li><a class="external text" title="http://tutor.lscf.ucsb.edu/instdev/sears/biochemistry/tw-enz/tabs-enzymes-frames.htm" href="http://tutor.lscf.ucsb.edu/instdev/sears/biochemistry/tw-enz/tabs-enzymes-frames.htm" rel="nofollow">Structure/Function of Enzymes</a>, Web tutorial on enzyme structure and function. </li> <li><a class="external text" title="http://www.ebi.ac.uk/intenz/spotlight.jsp" href="http://www.ebi.ac.uk/intenz/spotlight.jsp" rel="nofollow">Enzyme spotlight</a> Monthly feature at the European Bioinformatics Institute on a selected enzyme. </li> <li><a class="external text" title="http://www.amfep.org" href="http://www.amfep.org/" rel="nofollow">AMFEP</a>, Association of Manufacturers and Formulators of Enzyme Products </li> <li><a class="external text" title="http://www.brenda.uni-koeln.de" href="http://www.brenda.uni-koeln.de/" rel="nofollow">BRENDA</a> database, a comprehensive compilation of information and literature references about all known enzymes; requires payment by commercial users. </li> <li><a class="external text" title="http://www.ebi.ac.uk/thornton-srv/databases/enzymes/" href="http://www.ebi.ac.uk/thornton-srv/databases/enzymes/" rel="nofollow">Enzyme Structures Database</a> links to the known 3-D structure data of enzymes in the <a title="Protein Data Bank" href="http://en.wikipedia.org/wiki/Protein_Data_Bank">Protein Data Bank</a>. </li> <li><a class="external text" title="http://us.expasy.org/enzyme/" href="http://us.expasy.org/enzyme/" rel="nofollow">ExPASy enzyme</a> database, links to <a title="Swiss-Prot" href="http://en.wikipedia.org/wiki/Swiss-Prot">Swiss-Prot</a> sequence data, entries in other databases and to related literature searches. </li> <li><a class="external text" title="http://www.genome.jp/kegg/" href="http://www.genome.jp/kegg/" rel="nofollow">KEGG: Kyoto Encyclopedia of Genes and Genomes</a> Graphical and hypertext-based information on biochemical pathways and enzymes. </li> <li><a class="external text" title="http://www-mitchell.ch.cam.ac.uk/macie" href="http://www-mitchell.ch.cam.ac.uk/macie" rel="nofollow">MACiE</a> database of enzyme reaction mechanisms. </li> <li><a title="MetaCyc" href="http://en.wikipedia.org/wiki/MetaCyc">MetaCyc</a> database of enzymes and metabolic pathways </li> <li><a class="external text" title="http://www.vega.org.uk/video/programme/19" href="http://www.vega.org.uk/video/programme/19" rel="nofollow">'Face-to-Face Interview with Sir John Cornforth who was awarded a Nobel Prize for work on stereochemistry of enzyme-catalyzed reactions</a> Freeview video by the Vega Science Trust </li>

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