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[[Image:Triosephosphate isomerase.jpg|thumb|310px|Ribbon diagram of the enzyme [[triosephosphateisomerase|TIM]]. TIM is [[catalytically perfect enzyme|catalytically perfect]], meaning its conversion rate is limited, or nearly limited, to its substrate diffusion rate.]]
'''Enzymes''' are [[protein]]s that [[catalysis|catalyze]], or accelerate, [[biochemistry|biochemical]] [[chemical reaction|reaction]]s, a broad range of chemical reactions which take place in all living organisms. Enzymes are biochemical catalysts. In these reactions, the [[molecule]]s at the beginning of the process are called [[Substrate (biochemistry)|substrate]]s, and the enzyme converts these into different molecules: the products. Almost all processes in the [[cell (biology)|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.
Like all catalysts, enzymes work by providing an alternative [[Reaction coordinate|path]] of lower [[activation energy]] for a reaction and thus dramatically accelerate the rate of the reaction. A mechanical analogy of an enzyme would be a staircase, enabling changes in level by small increments. Some enzymes can make their conversion of substrate to product occur many millions of times faster. As with all catalysts, enzymes are not consumed by the reactions they catalyze, nor do they alter the [[Chemical equilibrium|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.<ref>{{cite journal|url=http://www.expasy.org/NAR/enz00.pdf|author= Bairoch A.|year= 2000|title= The ENZYME database in 2000 |journal=Nucleic Acids Res|volume=28|pages=304-305|id= PMID 10592255 }}</ref> Not all biochemical catalysts are proteins, since some [[RNA]] molecules called [[ribozyme]]s can also catalyze reactions.
Enzyme activity can be affected by other molecules. [[Enzyme inhibitor|Inhibitors]] are molecules that decrease enzyme activity, and activators are molecules that increase activity. [[Drug]]s and [[poison]]s are often enzyme inhibitors. Enzyme activity is also affected by [[temperature]], [[pH]], and the concentration of substrate. Some enzymes are used commercially, for example, in the synthesis of [[antibiotic]]s. In addition, some household cleaning products use enzymes to speed up biochemical reactions (''e.g.'', enzymes in biological washing powders break down protein or [[fat]] stains on clothes).
== 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>[http://etext.lib.virginia.edu/toc/modeng/public/Wil4Sci.html 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)]</ref>
In the 19th century, when studying the [[fermentation (food)|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 "[[Vitalism|ferments]]", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organisation of the yeast cells, not with the death or putrefaction of the cells."<ref>{{cite journal |author=Dubos J.|year= 1951|title= Louis Pasteur: Free Lance of Science, Gollancz. Quoted in Manchester K. L. (1995) Louis Pasteur (1822–1895)--chance and the prepared mind.|journal= Trends Biotechnol|volume=13|issue=12|pages=511-515|id= PMID 8595136}}</ref>
In 1878 German physiologist [[Wilhelm Kühne]] (1837–1900) coined the term ''[[wiktionary:enzyme|enzyme]]'', which comes from [[Greek language|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 [[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]</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]</ref> In 1907 he received the [[Nobel Prize in Chemistry]] "for his biochemical research and his discovery of cell-free fermentation".
Following Buchner; 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]</ref>
This discovery that enzymes could be crystalised 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.
==Structures and mechanisms==
[[Image:Carbonic anhydrase.jpg|thumb|right|300px|Ribbon-diagram showing the active sites of Carbonic anhydrase. The grey spheres are the [[zinc]] ions in the four active sites of this [[carbonic anhydrase]] enzyme and are held within two protein chains. Diagram drawn from [http://www.rcsb.org/pdb/explore.do?structureId=1DDZ PDB 1DDZ].]]
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]</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 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 one error 1 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 [[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>
Many enzymes that produce [[secondary metabolite]]s are [[promiscuous]], meaning 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====
[[Image:Induced fit diagram.png|thumb|400px|Diagrams to show the induced fit hypothesis of enzyme action.]]
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}}</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====
In 1958 [[Daniel Koshland]] suggested a modification to the lock and key model.<ref>{{cite journal|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> Since enzymes are rather flexible structures, the active site can be modified as the substrate interacts with the enzyme. As a result, the amino acid [[side chain]]s which make up the active site are molded into a precise shape which enables the enzyme to perform its catalytic function. In some cases the substrate molecule also changes shape slightly as it enters the active site.
====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 Feb 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 Nov 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 Nov 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> Agarwal PK, Billeter SR, Rajagopalan PT, Benkovic SJ, Hammes-Schiffer S. ''Network of coupled promoting motions in enzyme catalysis.'' Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2794-9. 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 Aug 24;43(33):10605-18. PMID: 15311922 </ref><ref>Tousignant A, Pelletier JN. ''Protein motions promote catalysis.'' Chem Biol. 2004 Aug;11(8):1037-42. 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==
===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 diagram above with four zinc cofactors bound in its active sites.<ref>{{cite journal |author= Mitsuhashi S, Mizushima T, Yamashita E, Yamamoto M, Kumasaka T, Moriyama H, Ueki T, Miyachi S, Tsukihara T.|year= 2000|title= X-ray structure of beta-carbonic anhydrase from the red alga, Porphyridium purpureum, reveals a novel catalytic site for CO(2) hydration.| journal=J Biol Chem.|volume= 275(8)|pages= 5521-5526|id= PMID 10681531}}</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 [[apoenzyme]]s. 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|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+ + 2e-) 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 cofactor NADH.<ref>[http://www.brenda.uni-koeln.de/ BRENDA The Comprehensive Enzyme Information System]</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.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 with all catalysts, all reactions catalyzed by enzymes must be "spontaneous" (containing a net negative [[Gibbs free energy]]). In the presence of an enzyme, a reaction runs in the same direction as it would without the enzyme, just more quickly. However, the uncatalyzed, "spontaneous" reaction might lead to different products than the catalyzed reaction. Furthermore, enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive" a thermodynamically unfavorable one. For example, the hydrolysis of [[Adenosine triphosphate|ATP]] is often used to drive other energetically unfavorable 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 physiological concentrations of the substrates and products have a large negative Gibbs free energy ([[exergonic]]), then the reaction is ''effectively'' irreversible. Under these conditions it is possible that the enzyme will only catalyze the reaction in one direction.
== Kinetics ==
{{main|Enzyme kinetics}}
[[Image:Simple mechanism.svg|thumb|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}}</ref> Their work was further developed by G. E. Briggs and [[J. B. S. Haldane]], who derived kinetic equations that are still widely used today.<ref> {{cite journal|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.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. 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]].
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.png|thumb|400px|A competitive inhibitor binds 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.]]
[[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.]]
{{main|Enzyme inhibition}}
Enzymes 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 as shown (''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 on the right.
'''Non-competitive inhibition'''
Non-competitive inhibitors never bind to the active site, but to other parts of the enzyme that can be far away from the substrate binding site (''right'', bottom). Moreover, non-competitive inhibitors only bind to the enzyme-substrate (ES) complex and not to 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 cannot be reversed. A class of these compounds called [[suicide inhibitor]]s includes [[eflornithine]] a drug used to treat the parasitic disease [[sleeping sickness]].
===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 can kill a pathogen but not its 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]] prosthetic groups of the enzyme [[cytochrome c oxidase]] and blocks [[cellular respiration]].
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. They also generate movement, with [[myosin]] hydrolysing ATP to generate [[muscle contraction]] and also moving cargo around the cell as part of the [[cytoskeleton]]. 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]].
[[Virus|Viruses]] can contain enzymes for infecting cells, such as the [[HIV]] [[integrase]] and [[reverse transcriptase]], or for viral release from cells, like the [[influenza]] virus [[neuraminidase]].
===Metabolism===
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 contant 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. However, if [[hexokinase]] is present, [[glucose-6-phosphate]] is the only product, as this reaction will occur most swiftly. Consequently, the network of metabolic pathways within each cell depends on the set of functional enzymes that are present.
==Control of activity==
There are four 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 |author=Faergeman N. J, Knudsen J.|year= 1997|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 with effective allocations of materials and energy economy, and it prevents the excess manufacture of 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 |author= Doble B. W., Woodgett J. R. |year=2003|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]].
==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]]. Mutation of this gene causes a single amino acid change in the enzyme [[phenylalanine hydroxylase]], which catalyzes the first step in the degradation of [[phenylalanine]]. The resulting build-up of phenylalanine and related products 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]</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 a description of what it does, with the word ending in ''-ase''. Examples are [[alcohol dehydrogenase]] and [[DNA polymerase]]. [[Kinase]]s are enzymes that transfer [[phosphate]] groups. This results in different enzymes with the same function having the same basic name; they are therefore distinguished by other characteristics, such as their optimal [[pH]] ([[alkaline phosphatase]]) or their ___location (membrane [[ATPase]]). Furthermore, the reversibility of chemical reactions means that the normal physiological direction of an enzyme reaction may not be seen under laboratory conditions. This can result in the same enzyme being identified with two different names: one coming from the laboratory identification and the other from its behavior in the cell. For instance, the enzyme formally known as ''xylitol:NAD+ 2-oxidoreductase (D-xylulose-forming)'' is more commonly referred to from the cellular viewpoint as ''D-xylulose reductase'', since the function of the enzyme in the cell is actually the reverse of what is often seen under laboratory conditions.
The [[International Union of Biochemistry and Molecular Biology]] and the [[International Union of Pure and Applied Chemistry]] have developed a [[nomenclature]] for enzymes, the [[EC number]]s; each enzyme is described by a sequence of four numbers preceded by "EC". However, this is not a perfect solution, as enzymes from different species or even very similar enzymes in the same species may have identical EC numbers.
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="4" | '''[[Detergent|Biological detergent]]'''[[Image:Washingpowder.jpg|180px|center|]]
|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 conditioners.
|-
|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;" rowspan="2"| '''[[Starch|Starch industry]]'''{{double image|center|Glucose Haworth.png|100|Alpha-D-Fructose-structure-corrected.png|100|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 (high fructose syrups derived from starchy materials have enhanced sweetening properties and lower [[calorie|calorific values]]).
|-
|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;" |'''[[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|ligninase]]s
|style="border-top: solid 3px #aaaaaa;" |Degrade starch to a lower [[viscosity]] product needed for sizing and coating paper. Xylanases reduce the amount of bleach required for decolorising; cellulases smooth fibers, enhance water drainage, and promote ink removal; lipases reduce pitch and lignin-degrading enzymes remove [[lignin]] from pulps to soften paper.
|-
|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]]
== References ==
<div class="references-small" style="-moz-column-count:2; column-count:2;">
<references/>
</div>
== Further reading ==
'''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
* M.V. Volkenshtein, R.R. [[Revaz Dogonadze|Dogonadze]], A.K. Madumarov, Z.D. Urushadze, Yu.I. Kharkats. Theory of Enzyme Catalysis.- ''Molekuliarnaya Biologia'', (1972), 431-439 (In Russian, English summary)
*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.
'''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]
'''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 1900's to the present times.
== External links ==
{{commons|Category:Enzymes}}
*[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.
* [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://us.expasy.org/enzyme/ ExPASy enzyme database], links to [[Swiss-Prot]] sequence data, entries in other databases and to related literature searches.
* [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://www-mitchell.ch.cam.ac.uk/macie MACiE], database of enzyme reaction mechanisms.
* [http://www.brenda.uni-koeln.de BRENDA], comprehensive compilation of information and literature references about all known enzymes; requires payment by commercial users.
* [http://www.genome.jp/kegg/ KEGG: Kyoto Encyclopedia of Genes and Genomes] Graphical and hypertext-based information on biochemical pathways and enzymes.
* [http://www.vega.org.uk/video/programme/19 'Face-to-Face Interview with Sir John Cornforth who was awarded a Noble Prize for work on stereochemistry of enzyme-catalyzed reactions] Freeview video by the Vega Science Trust
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