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[[Image:TPI1_structure.png|thumb|310px|[[Protein structure|Ribbon diagram]] of the enzyme [[triosephosphate isomerase|TIM]], surrounded by the [[space-filling model]] of the protein. TIM is an extremely efficient enzyme involved in the process that converts [[sugar]]s to energy in the body.]]
{{subpages}}
'''Enzymes''' are [[protein]]s that [[catalyst|catalyze]] (''i.e.'' [[reaction rate|accelerate]]) [[chemical reaction]]s.<ref>Smith AD (Ed) ''et. al.'' (1997) ''Oxford Dictionary of Biochemistry and Molecular Biology'' Oxford University Press ISBN 0-19-854768-4</ref> In enzymatic reactions, the [[molecule]]s at the beginning of the process are called [[Substrate (biochemistry)|substrate]]s, and the enzyme converts them into different molecules, the products. Almost all processes in a [[cell (biology)|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 pathway]]s occur in that cell.
'''Enzymes''' are [[protein]]s that [[catalyst|catalyze]] (''i.e.'' [[reaction rate|accelerate]]) [[chemical reaction]]s.<ref>Smith AD (Ed) ''et. al.'' (1997) ''Oxford Dictionary of Biochemistry and Molecular Biology'' Oxford University Press ISBN 0-19-854768-4</ref> In enzymatic reactions, the [[molecule]]s at the beginning of the process are called [[Substrate (biochemistry)|substrate]]s, and the enzyme converts them into different molecules, the products. Almost all processes in a [[cell (biology)|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 pathway]]s occur in that cell.


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== Etymology and history ==
== Etymology and history ==
[[Image:Eduardbuchner.jpg|thumb|175px|right|[[Eduard Buchner]]]]
As early as the late [[18th century|1700s]] and early [[19th century|1800s]], the digestion of [[meat]] by stomach secretions<ref name="Reaumur1752">{{cite journal | last = de Réaumur | first = RAF | authorlink = René Antoine Ferchault de Réaumur | year = 1752 | title = Observations sur la digestion des oiseaux | journal = Histoire de l'academie royale des sciences | volume = 1752|pages = 266, 461}}</ref> and the conversion of [[starch]] to [[sugar]]s by plant extracts and [[saliva]] were known. However, the mechanism by which this occurred had not been identified.<ref>Williams, H. S. (1904) [http://etext.lib.virginia.edu/toc/modeng/public/Wil4Sci.html  A History of Science: in Five Volumes. Volume IV: Modern Development of the Chemical and Biological Sciences] Harper and Brothers (New York) Accessed 04 April 2007</ref>
As early as the late [[18th century|1700s]] and early [[19th century|1800s]], the digestion of [[meat]] by stomach secretions<ref name="Reaumur1752">{{cite journal | last = de Réaumur | first = RAF | authorlink = René Antoine Ferchault de Réaumur | year = 1752 | title = Observations sur la digestion des oiseaux | journal = Histoire de l'academie royale des sciences | volume = 1752|pages = 266, 461}}</ref> and the conversion of [[starch]] to [[sugar]]s by plant extracts and [[saliva]] were known. However, the mechanism by which this occurred had not been identified.<ref>Williams, H. S. (1904) [http://etext.lib.virginia.edu/toc/modeng/public/Wil4Sci.html  A History of Science: in Five Volumes. Volume IV: Modern Development of the Chemical and Biological Sciences] Harper and Brothers (New York) Accessed 04 April 2007</ref>


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In 1897 [[Eduard Buchner]] began to study the ability of yeast extracts to ferment sugar despite the absence of living yeast cells. In a series of experiments at the [[Humboldt University of Berlin|University of Berlin]], he found that the sugar was fermented even when there were no living yeast cells in the mixture.<ref>[http://nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-bio.html Nobel Laureate Biography of Eduard Buchner at http://nobelprize.org] Accessed 04 April 2007</ref> He named the enzyme that brought about the fermentation of sucrose "[[zymase]]".<ref>[http://nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-lecture.html Text of Eduard Buchner's 1907 Nobel lecture at http://nobelprize.org] Accessed 04 April 2007</ref> 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 ''-ase'' is added to the name of the [[substrate (biochemistry)|substrate]] (''e.g.'', [[lactase]] is the enzyme that cleaves [[lactose]]) or the type of reaction (''e.g.'', [[DNA polymerase]] forms DNA polymers).
In 1897 [[Eduard Buchner]] began to study the ability of yeast extracts to ferment sugar despite the absence of living yeast cells. In a series of experiments at the [[Humboldt University of Berlin|University of Berlin]], he found that the sugar was fermented even when there were no living yeast cells in the mixture.<ref>[http://nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-bio.html Nobel Laureate Biography of Eduard Buchner at http://nobelprize.org] Accessed 04 April 2007</ref> He named the enzyme that brought about the fermentation of sucrose "[[zymase]]".<ref>[http://nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-lecture.html Text of Eduard Buchner's 1907 Nobel lecture at http://nobelprize.org] Accessed 04 April 2007</ref> 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 ''-ase'' is added to the name of the [[substrate (biochemistry)|substrate]] (''e.g.'', [[lactase]] is the enzyme that cleaves [[lactose]]) or the type of reaction (''e.g.'', [[DNA polymerase]] forms DNA polymers).


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 ''per se'' 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 [[John Howard Northrop|Northrop]] and [[Wendell Meredith Stanley|Stanley]], who worked on the digestive enzymes pepsin (1930), trypsin and chymotrypsin. These three scientists were awarded the 1946 Nobel Prize in Chemistry.<ref>[http://nobelprize.org/nobel_prizes/chemistry/laureates/1946/ 1946 Nobel prize for Chemistry laureates at http://nobelprize.org] Accessed 04 April 2007</ref>
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 e.


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 white]]s that digests the coating of some bacteria; the structure was solved by a group led by [[David Chilton Phillips]] and published in 1965.<ref>{{cite journal |author=Blake CC, Koenig DF, Mair GA, North AC, Phillips DC, Sarma VR.|year= 1965|title= Structure of hen egg-white lysozyme. A three-dimensional Fourier synthesis at 2 Angstrom resolution. |journal= Nature |volume=22|issue=206|pages=757–761|id= PMID 5891407}}</ref> 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.
==Attribution==
{{WPAttribution}}


==Structures and mechanisms==
==Footnotes==
<small>
<references>


{{see also|Enzyme catalysis}}
</references>
 
</small>[[Category:Suggestion Bot Tag]]
[[Image:Carbonic anhydrase.png|thumb|right|300px|Ribbon-diagram showing [[carbonic anhydrase|carbonic anhydrase II]]. The grey sphere is the [[zinc]] cofactor in the active site. Diagram drawn from [http://www.rcsb.org/pdb/explore.do?structureId=1MOO PDB 1MOO].]]
 
Enzymes are proteins, and range from just 62 amino acid residues in size for the [[monomer]] of [[4-Oxalocrotonate tautomerase|4-oxalocrotonate tautomerase]],<ref>{{cite journal |author=Chen LH, Kenyon GL, Curtin F, Harayama S, Bembenek ME, Hajipour G, Whitman CP |title=4-Oxalocrotonate tautomerase, an enzyme composed of 62 amino acid residues per monomer |journal=J. Biol. Chem. |volume=267 |issue=25 |pages=17716-21 |year=1992 |pmid=1339435}}</ref> to over 2,500 residues in the animal [[fatty acid synthase]].<ref>{{cite journal |author=Smith S |title=The animal fatty acid synthase: one gene, one polypeptide, seven enzymes |url=http://www.fasebj.org/cgi/reprint/8/15/1248 |journal=FASEB J. |volume=8 |issue=15 |pages=1248–59 |year=1994 |pmid=8001737}}</ref> The activities of enzymes are determined by their [[quaternary structure|three-dimensional structure]].<ref>{{cite journal|author=Anfinsen C.B.|year= 1973|title= Principles that Govern the Folding of Protein Chains|journal= Science|pages= 223–230|id= PMID 4124164}}</ref> Most enzymes are much larger than the substrates they act on, and only a very small portion of the enzyme (around 3–4 [[amino acid]]s) is directly involved in catalysis.<ref>[http://www.ebi.ac.uk/thornton-srv/databases/CSA/ The Catalytic Site Atlas at The European Bioinformatics Institute] Accessed 04 April 2007</ref> 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 [[Cofactor (biochemistry)|cofactors]], which are needed for catalysis. Some enzymes also have binding sites for small molecules, which are often direct or [[#Metabolic pathways|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.
 
Like all proteins, enzymes are made as long, linear chains of amino acids that [[protein folding|fold]] to produce a [[tertiary structure|three-dimensional product]]. Each unique amino acid sequence produces a unique structure, which has unique properties. Individual protein chains may sometimes group together to form a [[protein complex]]. Most enzymes can be [[denaturation (biochemistry)|denatured]]—that is, unfolded and inactivated—by heating, which destroys the [[Tertiary structure|three-dimensional structure]] of the protein. Depending on the enzyme, denaturation may be reversible or irreversible.
 
===Specificity===
Enzymes are usually very specific as to which reactions they catalyze and the [[substrate (biochemistry)|substrate]]s 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]].<ref>{{cite journal |author= Jaeger KE, Eggert T.|year= 2004|title= Enantioselective biocatalysis optimized by directed evolution.| journal=Curr Opin Biotechnol.|volume= 15(4)|pages= 305–313|id= PMID 15358000}}</ref>
 
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.<ref>{{cite journal |author= Shevelev IV, Hubscher U.|year= 2002|title= The 3' 5' exonucleases.| journal= Nat Rev Mol Cell Biol.|volume= 3|issue= 5|pages= 364–376|id= PMID 11988770}}</ref> This two-step process results in average error rates of less than 1 error in 100 million reactions in high-fidelity mammalian polymerases.<ref>Berg J., Tymoczko J. and Stryer L. (2002) ''Biochemistry.'' W. H. Freeman and Company ISBN 0-7167-4955-6</ref> Similar proofreading mechanisms are also found in [[RNA polymerase]],<ref>{{cite journal |author= Zenkin N, Yuzenkova Y, Severinov K.|year= 2006|title= Transcript-assisted transcriptional proofreading.| journal= Science.|volume= 313|pages= 518–520|id= PMID 16873663}}</ref> [[aminoacyl tRNA synthetase]]s<ref>{{cite journal |author= Ibba M, Soll D.|year= 2000|title= Aminoacyl-tRNA synthesis.| journal= Annu Rev Biochem.|volume= 69|pages= 617–650|id= PMID 10966471}}</ref> and [[ribosome]]s.<ref>{{cite journal |author= Rodnina MV, Wintermeyer W.|year= 2001|title= Fidelity of aminoacyl-tRNA selection on the ribosome: kinetic and structural mechanisms.| journal= Annu Rev Biochem.|volume= 70|pages= 415–435|id= PMID 11395413}}</ref>
 
Some enzymes that produce [[secondary metabolite]]s 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.<ref>{{cite web |url=http://www-users.york.ac.uk/~drf1/rdf_sp1.htm |title=The Screening Hypothesis - a new explanation of secondary product diversity and function |accessdate=2006-10-11 |last=Firn |first=Richard }}</ref>
 
===="Lock and key" model====
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.<ref>{{cite journal |author= Fischer E.|year= 1894|title= Einfluss der Configuration auf die Wirkung der Enzyme| journal=Ber. Dt.
Chem. Ges.|volume=27|pages=2985–2993|url = http://gallica.bnf.fr/ark:/12148/bpt6k90736r/f364.chemindefer }}</ref> 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.
 
====Induced fit model====
[[Image:Induced fit diagram.svg|thumb|450px|Diagrams to show the induced fit hypothesis of enzyme action.]]
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.<ref>{{cite journal|url=http://www.pnas.org/cgi/reprint/44/2/98|author=Koshland D. E.|year= 1958|title= Application of a Theory of Enzyme Specificity to Protein Synthesis|journal=Proc. Natl. Acad. Sci.|volume=44|issue=2|pages=98–104|id= PMID 16590179}}</ref> As a result, the substrate does not simply bind to a rigid active site, the amino acid [[side chain]]s 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.<ref>{{cite journal|author=Vasella A, Davies GJ, Bohm M.|year= 2002|title= Glycosidase mechanisms.|journal=Curr Opin Chem Biol.|volume=6|issue=5|pages=619–629|id= PMID 12413546}}</ref> The active site continues to change until the substrate is completely bound, at which point the final shape and charge is determined.<ref>{{cite book |last=Boyer |first=Rodney |title=Concepts in Biochemistry |origyear=2002 |accessdate=2007-04-21 |edition=2nd ed.|publisher=John Wiley & Sons, Inc. |location=New York, Chichester, Weinheim, Brisbane, Singapore, Toronto. |language=English |isbn=0-470-00379-0 |pages=137–138 |chapter=6}}</ref>
 
===Mechanisms===
 
Enzymes can act in several ways, all of which lower ΔG<sup>‡</sup>:<ref>Fersht, A (1985) ''Enzyme Structure and Mechanism'' (2nd ed) p50–52 W H Freeman & co, New York ISBN 0-7167-1615-1</ref>
 
*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).
 
*Providing an alternative pathway (e.g. temporarily reacting with the substrate to form an intermediate ES Complex which would be impossible in the absence of the enzyme).
 
*Reducing the reaction entropy change by bringing substrates together in the correct orientation to react. Considering ΔH<sup>‡</sup> alone overlooks this effect.
 
====Dynamics and function====
 
Recent investigations have provided new insights into the connection between internal dynamics of enzymes and their mechanism of catalysis.<ref> Eisenmesser EZ, Bosco DA, Akke M, Kern D. ''Enzyme dynamics during catalysis.'' Science. 2002 February 22;295(5559):1520–3. PMID: 11859194  </ref><ref> Agarwal PK. ''Role of protein dynamics in reaction rate enhancement by enzymes.'' J Am Chem Soc. 2005 November 2;127(43):15248-56. PMID: 16248667</ref><ref>Eisenmesser EZ, Millet O, Labeikovsky W, Korzhnev DM, Wolf-Watz M, Bosco DA, Skalicky JJ, Kay LE, Kern D. ''Intrinsic dynamics of an enzyme underlies catalysis.'' Nature. 2005 November 3;438(7064):117-21. PMID: 16267559</ref>
An enzyme's internal dynamics are described as the movement of internal parts (''e.g.'' 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.<ref>{{cite journal|url=http://www.structure.org/content/article/abstract?uid=PIIS096921260500167X|author=Yang LW, Bahar I.|title=Coupling between catalytic site and collective dynamics: A requirement for mechanochemical activity of enzymes.| journal=Structure.|year=2005|month=June|day=5|volume=13|pages=893–904|id=PMID 15939021}}</ref><ref>{{cite journal|url=http://www.pnas.org/cgi/content/full/99/5/2794|author=Agarwal PK, Billeter SR, Rajagopalan PT, Benkovic SJ, Hammes-Schiffer S.|title=Network of coupled promoting motions in enzyme catalysis.| journal=Proc. Natl. Acad. Sci. U S A.|year=2002|month=March|day=5|volume=99|pages=2794–9|id=PMID 11867722}}</ref><ref>Agarwal PK, Geist A, Gorin A. ''Protein dynamics and enzymatic catalysis: investigating the peptidyl-prolyl cis-trans isomerization activity of cyclophilin A.'' Biochemistry. 2004 August 24;43(33):10605-18. PMID: 15311922 </ref><ref>{{cite journal|url=http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VRP-4D4JYMC-6&_coverDate=08%2F31%2F2004&_alid=465962916&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=6240&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=613585a6164baa38b4f6536d8da9170a|author=Tousignant A, Pelletier JN.|title=Protein motions promote catalysis.|journal=Chem Biol.|year=2004|month=Aug|volume=11|issue=8|pages=1037–42|id=PMID 15324804}}</ref> 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, producing designer enzymes and developing new drugs.
 
===Allosteric modulation===
[[Allosteric]] enzymes change their structure in response to binding of [[effector (biology)|effector]]s. Modulation can be direct, where the effector binds directly to [[binding site]]s in the enzyme, or indirect, where the effector binds to other proteins or [[protein subunit]]s that interact with the allosteric enzyme and thus influence catalytic activity.
 
==Cofactors and coenzymes==
{{main|Cofactor (biochemistry)|Coenzyme}}
===Cofactors===
Some enzymes do not need any additional components to show full activity. However, others require non-protein molecules to be bound for activity. Cofactors can be either [[inorganic]] (''e.g.'', metal ions and [[iron-sulfur cluster]]s) or [[organic molecules|organic compounds]], (e.g., [[flavin]] and [[heme]]). Organic cofactors (coenzymes) are usually [[prosthetic groups]], which are tightly bound to the enzymes that they assist. These tightly-bound cofactors are distinguished from other coenzymes, such as [[Nicotinamide adenine dinucleotide|NADH]], since they are not released from the active site during the reaction.
 
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 in its active site.<ref>{{cite journal |author= Fisher Z, Hernandez Prada JA, Tu C, Duda D, Yoshioka C, An H, Govindasamy L, Silverman DN and McKenna R.|year= 2005|title= Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II.| journal=Biochemistry.|volume= 44(4)|pages= 1097-115|id= PMID 15667203}}</ref> 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.
 
Enzymes that require a cofactor but do not have one bound are called apoenzymes. An apoenzyme together with its cofactor(s) is called a '''holoenzyme''' (''i.e.'', 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 (''e.g.'', [[thiamine pyrophosphate]] in the enzyme [[pyruvate dehydrogenase]]).
 
===Coenzymes===
[[Image:NADH-3D-vdW.png|thumb|left|150px|[[Molecular_graphics#Space-filling_models|Space-filling model]] of the coenzyme NADH]]
Coenzymes are small molecules that transport chemical groups from one enzyme to another.<ref>AF Wagner, KA Folkers (1975) ''Vitamins and coenzymes.'' Interscience Publishers New York| ISBN 0-88275-258-8</ref> 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 [[nicotinamide adenine dinucleotide|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]].
 
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.<ref>[http://www.brenda.uni-koeln.de/ BRENDA The Comprehensive Enzyme Information System] Accessed 04 April 2007</ref>
 
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 ''S''-adenosylmethionine by methionine adenosyltransferase.
 
==Thermodynamics==
{{main |Activation energy|Thermodynamic equilibrium|Chemical equilibrium}}
[[Image:Activation2_updated.svg|thumb|300px|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.]]
 
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.
 
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 [[Adenosine triphosphate|ATP]] is often used to drive other chemical reactions.
 
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.
 
: <math>\mathrm{CO_2 + H_2O
{}^\mathrm{\quad Carbonic\ anhydrase}
\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!
\overrightarrow{\qquad\qquad\qquad\qquad}
H_2CO_3}</math> (in [[Biological tissue|tissue]]s; high CO<sub>2</sub> concentration)
: <math>\mathrm{H_2CO_3
{}^\mathrm{\quad Carbonic\ anhydrase}
\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!
\overrightarrow{\qquad\qquad\qquad\qquad}
CO_2 + H_2O}</math> (in [[lung]]s; low CO<sub>2</sub> concentration)
 
Nevertheless, if the equilibrium is greatly displaced in one direction, that is, in a very [[exergonic]] reaction, the reaction is ''effectively'' irreversible. Under these conditions the enzyme will, in fact, only catalyze the reaction in the thermodynamically allowed direction.
 
== Kinetics ==
{{main|Enzyme kinetics}}
[[Image:Simple mechanism.svg|thumb|left|300px|Mechanism for a single substrate enzyme catalyzed reaction. The enzyme (E) binds a substrate (S) and produces a product (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 assay]]s. In 1913 [[Leonor Michaelis]] and [[Maud Menten]] proposed a quantitative theory of enzyme kinetics, which is referred to as [[Michaelis-Menten kinetics]].<ref>{{cite journal|author=Michaelis L., Menten M.|year=1913|title= Die Kinetik der Invertinwirkung|journal=Biochem. Z.|volume= 49|pages= 333–369}} [http://web.lemoyne.edu/~giunta/menten.html English translation] Accessed 6 April 2007</ref> Their work was further developed by [[George Edward Briggs|G. E. Briggs]] and [[J. B. S. Haldane]], who derived kinetic equations that are still widely used today.<ref> {{cite journal|url=http://www.biochemj.org/bj/019/0338/bj0190338_browse.htm|author=Briggs G. E., Haldane J. B. S.|year=1925|title= A note on the kinetics of enzyme action|journal=Biochem. J.|volume=19|pages=339–339|id= PMID 16743508}}</ref>
 
The major contribution of Michaelis and Menten 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-Menten complex in their honor. The enzyme then catalyzes the chemical step in the reaction and releases the product.
 
[[Image:MM curve v3.png|thumb|300px|right|Saturation curve for an enzyme reaction showing the relation between the substrate concentration (S) and rate (''v'').''']]
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.<ref>{{cite journal |author=Radzicka A, Wolfenden R.|year= 1995|title= A proficient enzyme. |journal= Science |volume=6|issue=267|pages=90–931|id= PMID 7809611}}</ref> 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, shown 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 (''V''<sub>max</sub>) of the enzyme, all enzyme active sites are saturated with substrate, and the amount of ES complex is the same as the total amount of enzyme. 
 
However, ''V''<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]] (''K''<sub>m</sub>), which is the substrate concentration required for an enzyme to reach one-half its maximum velocity. Each enzyme has a characteristic ''K''<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 ''k''<sub>cat</sub>, which is the number of substrate molecules handled by one active site per second.
 
The efficiency of an enzyme can be expressed in terms of ''k''<sub>cat</sub>/''K''<sub>m</sub>. This is also called the specificity constant and incorporates the [[rate constant]]s 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 ''[[catalytically perfect enzyme|catalytically perfect]]'' or ''kinetically perfect''. Example of such enzymes are [[triosephosphateisomerase|triose-phosphate isomerase]], [[carbonic anhydrase]], [[acetylcholinesterase]], [[catalase]], fumarase, ß-lactamase, and [[superoxide dismutase]].
 
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.<ref>{{cite journal |author=Ellis RJ |title=Macromolecular crowding: obvious but underappreciated |journal=Trends Biochem. Sci. |volume=26 |issue=10 |pages=597-604 |year=2001 |pmid=11590012}}</ref> In these situations, a [[fractal]] [[Michaelis-Menten kinetics]] may be applied.<ref>{{cite journal |author=Kopelman R |title=Fractal Reaction Kinetics |journal=Science |volume=241 |issue=4873 |pages=1620–26 |year=1988 |DOI=10.1126/science.241.4873.1620}}</ref><ref>{{cite journal |author=Savageau MA |title=Michaelis-Menten mechanism reconsidered: implications of fractal kinetics |journal=J. Theor. Biol. |volume=176 |issue=1 |pages=115-24 |year=1995 |pmid=7475096}}</ref><ref>{{cite journal |author=Schnell S, Turner TE |title=Reaction kinetics in intracellular environments with macromolecular crowding: simulations and rate laws |journal=Prog. Biophys. Mol. Biol. |volume=85 |issue=2–3 |pages=235-60 |year=2004 |pmid=15142746}}</ref><ref>{{cite journal |author=Xu F, Ding H |title=A new kinetic model for heterogeneous (or spatially confined) enzymatic catalysis: Contributions from the fractal and jamming (overcrowding) effects |journal=Appl. Catal. A: Gen. |volume=317 |issue=1 |pages=70–81 |year=2007 |doi=10.1016/j.apcata.2006.10.014 }}</ref>
 
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 [[quantum tunneling|tunneling]] explanation, whereby a proton or an electron can tunnel through activation barriers, although for proton tunneling this model remains somewhat controversial.<ref>{{cite journal|author= Garcia-Viloca M., Gao J., Karplus M., Truhlar D. G.|year= 2004|title= How enzymes work: analysis by modern rate theory and computer simulations.|journal= Science|volume=303|issue=5655|pages=186–195|id= PMID 14716003}}</ref><ref>
{{cite journal|author=Olsson M. H., Siegbahn P. E., Warshel A.|year= 2004|title= Simulations of the large kinetic isotope effect and the temperature dependence of the hydrogen atom transfer in lipoxygenase|journal = J. Am. Chem. Soc.|volume=126|issue=9|pages=2820-1828|id= PMID 14995199}}</ref> Quantum tunneling for protons has been observed in [[tryptamine]].<ref>{{cite journal|author=Masgrau L., Roujeinikova A., Johannissen L. O., Hothi P., Basran J., Ranaghan K. E., Mulholland A. J., Sutcliffe M. J., Scrutton N. S., Leys D.|year= 2006|title= Atomic Description of an Enzyme Reaction Dominated by Proton Tunneling|journal= Science| volume=312|issue=5771|pages=237–241|id= PMID 16614214}}</ref>  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.
 
==Inhibition==
[[Image:Competitive inhibition.svg|thumb|400px|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.]]
 
{{main|Enzyme inhibitor}}
Enzyme reaction rates can be decreased by various types of [[enzyme inhibitor]]s.
 
===Reversible inhibitors===
 
'''Competitive inhibition'''
 
In competitive inhibition the inhibitor binds to the substrate binding site (figure ''right'', top, thus preventing substrate from binding (EI complex). 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 [[folic acid|dihydrofolate]] to [[folic acid|tetrahydrofolate]]. The similarity between the structures of folic acid and this drug are shown in the figure to the ''right'' bottom.
 
'''Non-competitive inhibition'''
 
Non-competitive inhibitors can bind either to the active site, or to other parts of the enzyme far away from the substrate-binding site. Moreover, non-competitive inhibitors bind to the enzyme-substrate (ES) complex and to the free enzyme. Their binding to this site changes the shape of the enzyme and stops the active site binding substrate(s). Consequently, since there is no direct competition between the substrate and inhibitor for the enzyme, the extent of inhibition depends only on the inhibitor concentration and will not be affected by the substrate concentration.
 
===Irreversible inhibitors===
 
Some enzyme inhibitors react with the enzyme and form a [[covalent bond|covalent]] adduct with the protein. The inactivation produced by this type of inhibitor is irreversible. A class of these compounds called [[suicide inhibitor]]s includes [[eflornithine]] a drug used to treat the parasitic disease [[sleeping sickness]].<ref name=Poulin>Poulin R, Lu L, Ackermann B, Bey P, Pegg AE. [http://www.jbc.org/cgi/reprint/267/1/150 ''Mechanism of the irreversible inactivation of mouse ornithine decarboxylase by alpha-difluoromethylornithine. Characterization of sequences at the inhibitor and coenzyme binding sites.''] J Biol Chem. 1992 Jan 5;267(1):150–8. PMID 1730582</ref> [[Penicillin]] and its derivatives 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 with amino acid residues.
 
[[Image:Methotrexate and folic acid compared.png||thumb|400px|right|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.]]
 
===Uses of inhibitors===
 
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, "''In all things there is a poison, and there is nothing without a poison.''"<ref>Ball, Philip (2006) ''The Devil's Doctor: Paracelsus and the World of Renaissance Magic and Science.'' Farrar, Straus and Giroux ISBN 0-374-22979-1</ref> Equally, [[antibiotics]] and other anti-infective drugs are just specific poisons that kill a pathogen but not its [[host (biology)|host]].
 
An example of an inhibitor being used as a drug is [[aspirin]], which inhibits the [[Cyclooxygenase|COX-1]] and [[Cyclooxygenase|COX-2]] enzymes that produce the [[inflammation]] messenger [[prostaglandin]], thus suppressing pain and inflammation. The poison [[cyanide]] is an irreversible enzyme inhibitor that combines with the copper and iron in the active site of the enzyme [[cytochrome c oxidase]] and blocks [[cellular respiration]].<ref>{{cite journal|url=http://www.jbc.org/cgi/reprint/265/14/7945|author=Yoshikawa S and Caughey WS.|year=1990|month=May|volume=265|issue=14|title= Infrared evidence of cyanide binding to iron and copper sites in bovine heart cytochrome c oxidase. Implications regarding oxygen reduction.|journal= J Biol Chem.|pages= 7945–7958|id= PMID 2159465}}</ref>
 
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 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]].
 
== Biological function ==
Enzymes serve a wide variety of functions inside living organisms. They are indispensable for [[signal transduction]] and cell regulation, often via [[kinase]]s and [[phosphatase]]s.<ref>{{cite journal |author= Hunter T.|year= 1995|title= Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling.|journal= Cell.|volume= 80(2)|pages= 225–236|id= PMID 7834742}}</ref>  They also generate movement, with [[myosin]] hydrolysing ATP to generate [[muscle contraction]] and also moving cargo around the cell as part of the [[cytoskeleton]].<ref>{{cite journal |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11294886|author= Berg JS, Powell BC, Cheney RE.|year= 2001|title= A millennial myosin census.|journal= Mol Biol Cell.|volume= 12(4)|pages= 780–794|id= PMID 11294886}}</ref> Other ATPases in the cell membrane are [[Ion pump (biology)|ion pumps]] involved in [[active transport]]. Enzymes are also involved in more exotic functions, such as [[luciferase]] generating light in [[Firefly|fireflies]].<ref>{{cite journal |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=2030669|author= Meighen EA.|year= 1991|title= Molecular biology of bacterial bioluminescence.|journal= Microbiol Rev.|volume= 55(1)|pages= 123–142|id= PMID 2030669}}</ref> [[Virus]]es 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]].
 
An  important function of enzymes is in the [[digestive systems]] of animals. Enzymes such as [[amylases]] and [[proteases]] break down large molecules ([[starch]] or [[protein]]s, respectively) into smaller ones, so they can be absorbed by the intestines. Starch is inabsorbable in 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, bacteria in the gut produce another enzyme, [[cellulase]] to break down the cellulose cell walls of plant fiber.
 
Several enzymes can work together in a specific order, creating [[metabolic pathway]]s. 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.
 
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 [[phosphorylation|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.
 
==Control of activity==
 
There are five main ways that enzyme activity is controlled in the cell.
 
#'''Enzyme production''' ([[Transcription (genetics)|transcription]] and [[Translation (genetics)|translation]] of enzyme genes) can be enhanced or diminished by a cell in response to changes in the cell's environment. This form of [[Regulation of gene expression|gene regulation]] is called [[enzyme induction and inhibition]]. For example, bacteria may become [[Antibiotic resistance|resistant to antibiotics]] such as [[penicillin]] because enzymes called [[beta-lactamase]]s are induced that hydrolyse the crucial [[Beta-lactam|beta-lactam ring]] within the penicillin molecule. Another example are enzymes in the [[liver]] called [[cytochrome P450 oxidase]]s, which are important in [[drug metabolism]]. Induction or inhibition of these enzymes can cause [[drug interaction]]s.
#Enzymes can be '''compartmentalized''', with different metabolic pathways occurring in different [[cellular compartment]]s. 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]].<ref>{{cite journal |url=http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1218279&blobtype=pdf|author=Faergeman N. J, Knudsen J.|year= 1997|month=April|title= Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling|journal= Biochem J|volume=323|pages=1–12|id= PMID 9173866}}</ref>
#Enzymes can be regulated by '''[[Enzyme inhibitor|inhibitors]] and activators'''. 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 ''committed step''), thus regulating the amount of end product made by the pathways. Such a regulatory mechanism is called a [[negative feedback|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 [[homeostasis|homeostatic devices]], the control of enzymatic action helps to maintain a stable internal environment in living organisms.
#Enzymes can be regulated through '''[[post-translational modification]]'''. This can include [[phosphorylation]], [[Myristic acid|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]].<ref>{{cite journal |url=http://jcs.biologists.org/cgi/content/full/116/7/1175|author= Doble B. W., Woodgett J. R. |year=2003|month=April|title= GSK-3: tricks of the trade for a multi-tasking kinase|journal=J. Cell. Sci.|volume=116|pages=1175–1186|id= PMID 12615961}}</ref> 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]].
#Some enzymes may become '''activated when localized to a different environment''' (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 (biology)|vesicle]] causing its activation.<ref>{{cite journal|url=http://dx.doi.org/10.1016/0092-8674(93)90260-W|author=Carr C. M., Kim P. S. |year=2003|month=April|title= A spring-loaded mechanism for the conformational change of influenza hemagglutinin|journal=Cell|volume=73|pages=823–832|id= PMID 8500173}}</ref>
 
==Involvement in disease==
[[Image:Phenylalanine hydroxylase brighter.jpg|thumb|200px|[[Phenylalanine hydroxylase]]. Created from [http://www.rcsb.org/pdb/explore.do?structureId=1KW0 PDB 1KW0] ]]
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.
 
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.<ref> [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.234 Phenylketonuria: NCBI Genes and Disease] Accessed 04 April 2007</ref>
 
Another example is when [[germline mutation]]s 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.
 
== Naming conventions ==
 
An enzyme's name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in '''''-ase'''''. 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. ''E.g.'' [[Glucose isomerase]], used industrially to convert [[glucose]] into the sweetener [[fructose]], is a xylose isomerase ''in vivo''.
 
The [[International Union of Biochemistry and Molecular Biology]] have developed a [[wikt:nomenclature|nomenclature]] for enzymes, the '''[[EC number]]s'''; each enzyme is described by a sequence of four numbers preceded by "EC".
The first number broadly classifies the enzyme based on its mechanism:
 
The top-level classification is
* EC 1 ''[[Oxidoreductase]]s'': catalyze [[oxidation]]/reduction reactions
* EC 2 ''[[Transferase]]s'': transfer a [[functional group]] (''e.g.'' a methyl or phosphate group)
* EC 3 ''[[Hydrolase]]s'': catalyze the [[hydrolysis]] of various bonds
* EC 4 ''[[Lyase]]s'': cleave various bonds by means other than hydrolysis and oxidation
* EC 5 ''[[Isomerase]]s'': catalyze [[isomer]]ization changes within a single molecule
* EC 6 ''[[Ligase]]s'': join two molecules with [[covalent bond]]s
 
The complete nomenclature can be browsed at http://www.chem.qmul.ac.uk/iubmb/enzyme/.
 
==Industrial applications==
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 solvent]]s 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 ''in vitro'' evolution.<ref>{{cite journal|author=Renugopalakrishnan V, Garduno-Juarez R, Narasimhan G, Verma CS, Wei X, Li P.|year= 2005|title= Rational design of thermally stable proteins: relevance to bionanotechnology.|journal= J Nanosci Nanotechnol.|volume=5|issue=11|pages= 1759–1767|id= PMID 16433409}}</ref><ref>{{cite journal|author=Hult K, Berglund P.|year= 2003|title= Engineered enzymes for improved organic synthesis.|journal= Curr Opin Biotechnol.|volume=14|issue=4|pages= 395–400|id= PMID 12943848}}</ref>
 
{| class="wikitable"
|-
|width=24%  align=center|'''Application'''
|width=38%  align=center|'''Enzymes used'''
|width=38%  align=center|'''Uses'''
|-
|style="border-top: solid 3px #aaaaaa;" rowspan="2" | '''[[Baking|Baking industry]]''' [[Image:Amylose.svg|thumb|center|180px|alpha-amylase catalyzes the release of sugar monomers from starch]]
|style="border-top: solid 3px #aaaaaa;" |[[Fungus|Fungal]] alpha-amylase enzymes are normally inactivated at about 50 degrees Celsius, but are destroyed during the baking process.
|style="border-top: solid 3px #aaaaaa;" |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.
|-
| Proteases
| Biscuit manufacturers use them to lower the protein level of flour.
|-
|style="border-top: solid 3px #aaaaaa;" |'''[[Baby food]]s'''
|style="border-top: solid 3px #aaaaaa;" |[[Trypsin]]
|style="border-top: solid 3px #aaaaaa;" |To predigest baby foods.
|-
|style="border-top: solid 3px #aaaaaa;" rowspan="6" | '''[[Brewing|Brewing industry]]''' [[Image:Sjb whiskey malt.jpg|thumb|center|180px|Germinating [[barley]] used for malt.]]
|style="border-top: solid 3px #aaaaaa;" | Enzymes from barley are released during the mashing stage of beer production.
|style="border-top: solid 3px #aaaaaa;" | They degrade starch and proteins to produce simple sugar, amino acids and peptides that are used by yeast for fermentation.
|-
| Industrially produced barley enzymes
| Widely used in the brewing process to substitute for the natural enzymes found in barley.
|-
| Amylase, glucanases, proteases
| Split polysaccharides and proteins in the [[malt]].
|-
| Betaglucosidase
| Improve the filtration characteristics.
|-
| Amyloglucosidase
| Low-calorie [[beer]].
|-
| Proteases
| Remove cloudiness produced during storage of beers.
|-
|style="border-top: solid 3px #aaaaaa;" | '''[[Juice|Fruit juices]]'''
|style="border-top: solid 3px #aaaaaa;" | Cellulases, pectinases
|style="border-top: solid 3px #aaaaaa;" | Clarify fruit juices
|-
|style="border-top: solid 3px #aaaaaa;" rowspan="4" | '''[[Dairy|Dairy industry]]'''  [[Image:Roquefort cheese.jpg|thumb|center|180px|Roquefort cheese]]
|style="border-top: solid 3px #aaaaaa;" |[[Rennin]], derived from the stomachs of young [[ruminant|ruminant animals]] (like calves and lambs).
|style="border-top: solid 3px #aaaaaa;" |Manufacture of cheese, used to [[hydrolyze]] protein.
|-
| Microbially produced enzyme
| Now finding increasing use in the dairy industry.
|-
| [[Lipase]]s
| Is implemented during the production of [[Roquefort cheese]] to enhance the ripening of the [[Danish Blue cheese|blue-mould cheese]].
|-
| Lactases
| Break down [[lactose]] to [[glucose]] and galactose.
|-
|style="border-top: solid 3px #aaaaaa;" |'''[[tenderizing|Meat tenderizers]]'''
|style="border-top: solid 3px #aaaaaa;" |[[Papain]]
|style="border-top: solid 3px #aaaaaa;" |To soften meat for cooking.
|-
|style="border-top: solid 3px #aaaaaa;" rowspan="2"| '''[[Starch|Starch industry]]'''{{double image|center|Alpha-D-Glucopyranose.svg|90|Alpha-D-Fructofuranose.svg|110|Glucose|Fructose}}
|style="border-top: solid 3px #aaaaaa;" | Amylases, amyloglucosideases and glucoamylases
|style="border-top: solid 3px #aaaaaa;" | Converts [[starch]] into [[glucose]] and various [[Inverted sugar syrup|syrups]].
|-
| Glucose isomerase
| Converts [[glucose]] into [[fructose]] in production of [[High-fructose corn syrup|high fructose syrups]] from starchy materials. These syrups have enhanced sweetening properties and lower [[calorie|calorific values]] than sucrose for the same level of sweetness.
|-
|style="border-top: solid 3px #aaaaaa;" |'''[[Paper|Paper industry]]'''[[Image:InternationalPaper6413.jpg|160px|thumb|center|A paper mill in [[South Carolina]].]]
|style="border-top: solid 3px #aaaaaa;" |[[Amylase]]s, [[Xylanase]]s, [[Cellulase]]s and [[lignin]]ases
|style="border-top: solid 3px #aaaaaa;" |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.
|-
|style="border-top: solid 3px #aaaaaa;" rowspan="2" |'''[[Biofuel]] industry'''[[Image:Cellulose-3D-balls.png|180px|thumb|center|Cellulose in 3D]]
|style="border-top: solid 3px #aaaaaa;" |[[Cellulase]]s
|style="border-top: solid 3px #aaaaaa;" |Used to break down cellulose into sugars that can be fermented (see [[cellulosic ethanol]]).
|-
| [[Ligninase]]s
| Use of [[lignin]] waste
|-
|style="border-top: solid 3px #aaaaaa;" rowspan="4" | '''[[Detergent|Biological detergent]]'''[[Image:Washingpowder.jpg|180px|thumb|center|Laundry soap]]
|style="border-top: solid 3px #aaaaaa;" |Primarily [[protease]]s, produced in an [[extracellular]] form from [[bacteria]]
|style="border-top: solid 3px #aaaaaa;" |Used for presoak conditions and direct liquid applications helping with removal of protein stains from clothes.
|-
| [[Amylase]]s
| Detergents for machine dish washing to remove resistant starch residues.
|-
| [[Lipase]]s
| Used to assist in the removal of fatty and oily stains.
|-
| [[Cellulase]]s
| Used in biological fabric [[conditioner]]s.
|-
|style="border-top: solid 3px #aaaaaa;" |'''[[Contact lens|Contact lens cleaners]]'''
|style="border-top: solid 3px #aaaaaa;" |[[Proteases]]
|style="border-top: solid 3px #aaaaaa;" |To remove [[proteins]] on [[contact lens]] to prevent infections.
|-
|style="border-top: solid 3px #aaaaaa;" |'''[[Rubber|Rubber industry]]'''
|style="border-top: solid 3px #aaaaaa;" |[[Catalase]]
|style="border-top: solid 3px #aaaaaa;" |To generate [[oxygen]] from [[peroxide]] to convert [[latex]] into foam rubber.
|-
|style="border-top: solid 3px #aaaaaa;" |'''[[Photography|Photographic industry]]'''
|style="border-top: solid 3px #aaaaaa;" |Protease (ficin)
|style="border-top: solid 3px #aaaaaa;" |Dissolve [[gelatin]] off scrap [[Photographic film|film]], allowing recovery of its [[silver]] content.
|-
|style="border-top: solid 3px #aaaaaa;" |'''[[Molecular biology]]''' [[Image:DNA123 rotated.png|180px|thumb|center|Part of the DNA [[double helix]].]]
|style="border-top: solid 3px #aaaaaa;" |[[Restriction enzyme]]s, [[DNA ligase]] and [[polymerases]]
|style="border-top: solid 3px #aaaaaa;" |Used to manipulate DNA in [[genetic engineering]], important in [[pharmacology]], [[agriculture]] and [[medicine]]. Essential for [[Restriction enzyme|restriction digestion]] and the [[polymerase chain reaction]]. Molecular biology is also important in [[forensic science]].
|-
|}
 
== See also ==
 
* [[Enzyme kinetics]]
* [[Enzyme inhibitor]]
* [[Enzyme assay]]
* [[Enzyme catalysis]]
* [[SUMO enzymes]]
* [[Ki Database|K<sub>i</sub> Database]]
* [[Proteonomics]] and [[protein engineering]]
 
== References ==
<div class="reflist4" style="height: 220px; overflow: auto; padding: 3px" >
<references/>
</div>
 
== Further reading ==
{{Col-begin}}
{{col-break}}
'''Etymology and history'''
*[http://bip.cnrs-mrs.fr/bip10/buchner.htm 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.
*[http://etext.lib.virginia.edu/toc/modeng/public/Wil4Sci.html 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.
*Kleyn, J. and Hough J. The Microbiology of Brewing. ''Annual Review of Microbiology'' (1971) Vol. 25: 583–608
 
'''Enzyme structure and mechanism'''
*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
*Walsh, C., Enzymatic Reaction Mechanisms. W. H. Freeman and Company. 1979. ISBN 0-7167-0070-0
*Page, M. I., and Williams, A. (Eds.), 1987. Enzyme Mechanisms. Royal Society of Chemistry. ISBN 0-85186-947-5
* Bugg, T. Introduction to Enzyme and Coenzyme Chemistry, 2004, Blackwell Publishing Limited; 2nd edition. ISBN 1-40511-452-5
*Warshel, A., Computer Modeling of Chemical Reactions in enzymes and Solutions John Wiley & Sons Inc. 1991. ISBN 0-471-18440-3
 
'''Thermodynamics'''
*[http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookEnzym.html Reactions and Enzymes] Chapter 10 of On-Line Biology Book at Estrella Mountain Community College.
 
{{col-break}}
 
'''Kinetics and inhibition'''
 
*Athel Cornish-Bowden, ''Fundamentals of Enzyme Kinetics''. (3rd edition), Portland Press (2004), ISBN 1-85578-158-1.
*Irwin H. Segel, ''Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems''. Wiley-Interscience; New Ed edition (1993), ISBN 0-471-30309-7.
*John W. Baynes, ''Medical Biochemistry'', Elsevier-Mosby; 2th Edition (2005), ISBN 0-7234-3341-0, p. 57.
 
'''Function and control of enzymes in the cell'''
 
*Price, N. and Stevens, L., Fundamentals of Enzymology: Cell and Molecular Biology of Catalytic Proteins Oxford University Press, (1999), ISBN 0-19-850229-X
*[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.chapter.86 Nutritional and Metabolic Diseases] Chapter of the on-line textbook "Introduction to Genes and Disease" from the NCBI.
 
'''Enzyme-naming conventions'''
*[http://www.chem.qmul.ac.uk/iubmb/enzyme/ Enzyme Nomenclature], Recommendations for enzyme names from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology.
* Koshland D. The Enzymes, v. I, ch. 7, Acad. Press, New York, (1959)
 
'''Industrial applications'''
*[http://www.mapsenzymes.com/History_of_Enzymes.asp History of industrial enzymes], Article about the history of industrial enzymes, from the late 1900s to the present times.
 
{{Col-end}}
 
== External links ==
{{commonscat|Enzymes}}
{{portal|Food}}
 
*[http://tutor.lscf.ucsb.edu/instdev/sears/biochemistry/tw-enz/tabs-enzymes-frames.htm Structure/Function of Enzymes], Web tutorial on enzyme structure and function.
* {{McGrawHillAnimation|biochemistry|Enzyme%20Action%20and%20the%20Hydrolysis%20of%20Sucrose}}
* [http://www.ebi.ac.uk/intenz/spotlight.jsp Enzyme spotlight] Monthly feature at the European Bioinformatics Institute on a selected enzyme.
* [http://www.biiuk.com UK biotech and pharmaceutical industry] The Biosystems Informatics Institute (Bii) is a new UK government initiative funded by the Department of Trade and Industry and the Regional Development Agency, One NorthEast. From its outset the Institute will undertake industry-facing research and development in collaboration with the UK biotech and pharmaceutical industry.
* [http://www.amfep.org AMFEP], Association of Manufacturers and Formulators of Enzyme Products
* [http://www.brenda.uni-koeln.de BRENDA] database, a comprehensive compilation of information and literature references about all known enzymes; requires payment by commercial users.
* [http://www.ebi.ac.uk/thornton-srv/databases/enzymes/ Enzyme Structures Database] links to the known 3-D structure data of enzymes in the [[Protein Data Bank]].
* [http://us.expasy.org/enzyme/ ExPASy enzyme] database, links to  [[Swiss-Prot]] sequence data, entries in other databases and to related literature searches.
* [http://www.genome.jp/kegg/ KEGG: Kyoto Encyclopedia of Genes and Genomes] Graphical and hypertext-based information on biochemical pathways and enzymes.
* [http://www-mitchell.ch.cam.ac.uk/macie MACiE] database of enzyme reaction mechanisms.
* [[MetaCyc]] database of enzymes and metabolic pathways
* [http://www.vega.org.uk/video/programme/19 'Face-to-Face Interview with Sir John Cornforth who was awarded a Nobel Prize for work on stereochemistry of enzyme-catalyzed reactions] Freeview video by the Vega Science Trust
 
{{featured article}}
 
{{BranchesofFoodChemistry}}
{{Enzymes}}
 
<!--[[Category:Biomolecules]]
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Enzymes are proteins that catalyze (i.e. accelerate) chemical reactions.[1] 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.

Like all catalysts, enzymes work by lowering the activation energy (Ea or ΔG‡) 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.[2] Although all enzymes are proteins, not all biochemical catalysts are enzymes, since some RNA molecules called ribozymes also catalyze reactions.[3] Other synthetic molecules called artificial enzymes, can also display enzyme-like catalysis.[4]

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, 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 (e.g., 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).

Etymology and history

As early as the late 1700s and early 1800s, the digestion of meat by stomach secretions[5] 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.[6]

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."[7]

In 1878 German physiologist Wilhelm Kühne (1837–1900) coined the term enzyme, which comes from Greek ενζυμον "in leaven", to describe this process. The word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment used to refer to chemical activity produced by living organisms.

In 1897 Eduard Buchner began to study the ability of yeast extracts to ferment sugar despite the absence of living yeast cells. 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.[8] He named the enzyme that brought about the fermentation of sucrose "zymase".[9] 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 -ase is added to the name of the substrate (e.g., lactase is the enzyme that cleaves lactose) or the type of reaction (e.g., DNA polymerase forms DNA polymers).

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 e.

Attribution

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Footnotes

  1. ↑ Smith AD (Ed) et. al. (1997) Oxford Dictionary of Biochemistry and Molecular Biology Oxford University Press ISBN 0-19-854768-4
  2. ↑ Bairoch A. (2000). "The ENZYME database in 2000". Nucleic Acids Res 28: 304–305. PMID 10592255.
  3. ↑ Lilley D (2005). "Structure, folding and mechanisms of ribozymes". Curr Opin Struct Biol 15 (3): 313-23. PMID 15919196.
  4. ↑ Groves JT (1997). "Artificial enzymes. The importance of being selective". Nature 389 (6649): 329-30. PMID 9311771.
  5. ↑ de Réaumur, RAF (1752). "Observations sur la digestion des oiseaux". Histoire de l'academie royale des sciences 1752: 266, 461.
  6. ↑ Williams, H. S. (1904) A History of Science: in Five Volumes. Volume IV: Modern Development of the Chemical and Biological Sciences Harper and Brothers (New York) Accessed 04 April 2007
  7. ↑ Dubos J. (1951). "Louis Pasteur: Free Lance of Science, Gollancz. Quoted in Manchester K. L. (1995) Louis Pasteur (1822–1895)—chance and the prepared mind.". Trends Biotechnol 13 (12): 511–515. PMID 8595136.
  8. ↑ Nobel Laureate Biography of Eduard Buchner at http://nobelprize.org Accessed 04 April 2007
  9. ↑ Text of Eduard Buchner's 1907 Nobel lecture at http://nobelprize.org Accessed 04 April 2007

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