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{{short description|Large biological molecule that acts as a catalyst}}
{{redirect|Biocatalyst|the use of natural catalysts in organic chemistry|Biocatalysis}}
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[[File:Glucosidase enzyme.png|thumb|400px|The enzyme [[glucosidase]] converts the sugar [[maltose]] into two [[glucose]] sugars. [[Active site]] residues in red, maltose substrate in black, and [[Nicotinamide adenine dinucleotide|NAD]] [[Cofactor (biochemistry)|cofactor]] in yellow. ({{PDB|1OBB}})|alt=Ribbon diagram of glycosidase with an arrow showing the cleavage of the maltose sugar substrate into two glucose products.]]
{{Biochemistry sidebar}}
An '''enzyme''' is a [[biological macromolecule]], usually a [[protein]], that acts as a biological [[catalyst]], accelerating [[chemical reactions]] without being consumed in the process. The [[molecules]] on which enzymes act are called [[substrate (chemistry)|substrates]], which are converted into [[product (chemistry)|products]]. Nearly all [[metabolism|metabolic processes]] within a [[cell (biology)|cell]] depend on [[enzyme catalysis]] to occur at biologically relevant rates.<ref name = "Stryer_2002">{{cite book |vauthors=Stryer L, Berg JM, Tymoczko JL | title = Biochemistry | publisher = W.H. Freeman | location = San Francisco | year = 2002 | edition = 5th | isbn = 0-7167-4955-6 | url = https://www.ncbi.nlm.nih.gov/books/NBK21154/| archive-url = https://web.archive.org/web/20101210225405/http://www.ncbi.nlm.nih.gov/books/NBK21154/| url-status = dead| archive-date = 10 December 2010}}{{Open access}}</ref>{{rp|8.1}} [[Metabolic pathway]]s are typically composed of a series of enzyme-catalyzed steps. The study of enzymes is known as ''enzymology'', and a related field focuses on [[pseudoenzyme]]s—proteins that have lost catalytic activity but may retain regulatory or scaffolding functions, often indicated by alterations in their [[amino acid]] sequences or unusual 'pseudocatalytic' behavior.<ref>{{cite journal | vauthors = Murphy JM, Farhan H, Eyers PA | title = Bio-Zombie: the rise of pseudoenzymes in biology | journal = Biochemical Society Transactions | volume = 45 | issue = 2 | pages = 537–544 | date = April 2017 | pmid = 28408493 | doi = 10.1042/bst20160400 }}</ref><ref name="pmid24107129">{{cite journal | vauthors = Murphy JM, Zhang Q, Young SN, Reese ML, Bailey FP, Eyers PA, Ungureanu D, Hammaren H, Silvennoinen O, Varghese LN, Chen K, Tripaydonis A, Jura N, Fukuda K, Qin J, Nimchuk Z, Mudgett MB, Elowe S, Gee CL, Liu L, Daly RJ, Manning G, Babon JJ, Lucet IS | title = A robust methodology to subclassify pseudokinases based on their nucleotide-binding properties | journal = The Biochemical Journal | volume = 457 | issue = 2 | pages = 323–334 | date = January 2014 | pmid = 24107129 | pmc = 5679212 | doi = 10.1042/BJ20131174 }}</ref>

Enzymes are known to catalyze over 5,000 types of biochemical reactions.<ref>{{cite journal | vauthors = Schomburg I, Chang A, Placzek S, Söhngen C, Rother M, Lang M, Munaretto C, Ulas S, Stelzer M, Grote A, Scheer M, Schomburg D | title = BRENDA in 2013: integrated reactions, kinetic data, enzyme function data, improved disease classification: new options and contents in BRENDA | journal = Nucleic Acids Research | volume = 41 | issue = Database issue | pages = D764–D772 | date = January 2013 | pmid = 23203881 | pmc = 3531171 | doi = 10.1093/nar/gks1049 }}</ref> Other biological catalysts include [[Ribozyme|catalytic RNA molecules]], or [[ribozyme]]s, which are sometimes classified as enzymes despite being composed of RNA rather than protein. More recently, [[biomolecular condensate]]s have been recognized as a third category of biocatalysts, capable of catalyzing reactions by creating interfaces and gradients—such as ionic gradients—that drive biochemical processes, even when their component proteins are not intrinsically catalytic.<ref name=Ball-2025-01-21>{{cite journal |date=2025-01-21 |author=Philip Ball |editor=Jen Schwartz |title=Mysterious Blobs Found inside Cells Are Rewriting the Story of How Life Works. Tiny specks called biomolecular condensates are leading to a new understanding of the cell |journal=Scientific American |volume=332 |issue=2 (February) |url=https://www.scientificamerican.com/article/mysterious-blobs-found-in-cells-are-rewriting-how-life-works/ |quote=Condensates can act as catalysts for biochemical reactions, even if their component proteins do not. This is because condensates create an interface between two phases, which sets up a gradient in concentrations—of ions for example, creating an electric field that can trigger reactions. The researchers have demonstrated condensate-induced catalysis of a wide range of biochemical reactions, including those involving hydrolysis (in which water splits other molecules apart).}}</ref>

Enzymes increase the [[reaction rate]] by lowering a reaction's [[activation energy]], often by factors of millions. A striking example is [[orotidine 5'-phosphate decarboxylase]], which accelerates a reaction that would otherwise take millions of years to occur in milliseconds.<ref name="radzicka">{{cite journal | vauthors = Radzicka A, Wolfenden R | title = A proficient enzyme | journal = Science | volume = 267 | issue = 5194 | pages = 90–93 | date = January 1995 | pmid = 7809611 | doi = 10.1126/science.7809611 | s2cid = 8145198 | bibcode = 1995Sci...267...90R }}</ref><ref name="pmid17889251">{{cite journal | vauthors = Callahan BP, Miller BG | title = OMP decarboxylase--An enigma persists | journal = Bioorganic Chemistry | volume = 35 | issue = 6 | pages = 465–469 | date = December 2007 | pmid = 17889251 | doi = 10.1016/j.bioorg.2007.07.004 }}</ref> Like all catalysts, enzymes do not affect the overall [[Chemical equilibrium|equilibrium]] of a reaction and are regenerated at the end of each cycle. What distinguishes them is their high specificity, determined by their unique [[tertiary structure|three-dimensional structure]], and their sensitivity to factors such as [[temperature]] and [[pH]]. Enzyme activity can be enhanced by [[enzyme activator|activators]] or diminished by [[Enzyme inhibitor|inhibitors]], many of which serve as [[drug]]s or [[poison]]s. Outside optimal conditions, enzymes may lose their structure through [[Denaturation (biochemistry)|denaturation]], leading to loss of function.

Enzymes have widespread practical applications. In industry, they are used to catalyze the production of [[antibiotic]]s and other complex molecules. In everyday life, enzymes in [[Detergent enzymes|biological washing powders]] break down protein, starch, and [[fat]] stains, enhancing cleaning performance. [[Papain]] and other proteolytic enzymes are used in [[meat tenderizer]]s to hydrolyze proteins, improving texture and digestibility. Their specificity and efficiency make enzymes indispensable in both biological systems and commercial processes.

[[File:IUPAC definition for enzymes.png|thumb|right|550px|link=https://doi.org/10.1351/goldbook.E02159|IUPAC definition for enzymes]]
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== Etymology and history ==
By the late 17th and early 18th centuries, the digestion of [[meat]] by stomach secretions<ref name="Reaumur1752">{{cite journal |author-link=René Antoine Ferchault de Réaumur |vauthors=de Réaumur RA |year=1752 |title=Observations sur la digestion des oiseaux |url=https://gallica.bnf.fr/ark:/12148/bpt6k35505/f452.item |journal=Histoire de l'Académie Royale des Sciences |language=fr |volume=1752 |pages=266, 461}}</ref> and the conversion of [[starch]] to [[sugar]]s by plant extracts and [[saliva]] were known but the mechanisms by which these occurred had not been identified.<ref>{{cite book | url = http://etext.lib.virginia.edu/toc/modeng/public/Wil4Sci.html | vauthors = Williams HS | title = A History of Science: in Five Volumes''. ''Volume IV: Modern Development of the Chemical and Biological Sciences | publisher = Harper and Brothers | year = 1904 }}</ref><!--adjacent info: [[Jöns Jacob Berzelius]], [[α-Amylase#Salivary_amylase_(ptyalin)]], [[amylase#History]]-->

French chemist [[Anselme Payen]] was the first to discover an enzyme, [[diastase]], in 1833.<ref>{{cite journal | vauthors = Payen A, Persoz JF | year = 1833 | title = Mémoire sur la diastase, les principaux produits de ses réactions et leurs applications aux arts industriels | language = fr | trans-title = Memoir on diastase, the principal products of its reactions, and their applications to the industrial arts | journal = Annales de chimie et de physique | series = 2nd | volume = 53 | url = https://books.google.com/books?id=Q9I3AAAAMAAJ&pg=PA73 | pages = 73–92}}</ref> A few decades later, when studying the [[fermentation (food)|fermentation]] of sugar to [[ethanol|alcohol]] by [[yeast]], [[Louis Pasteur]] concluded that this fermentation was caused 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."<ref>{{cite journal | vauthors = Manchester KL | title = Louis Pasteur (1822–1895)--chance and the prepared mind | journal = Trends in Biotechnology | volume = 13 | issue = 12 | pages = 511–515 | date = December 1995 | pmid = 8595136 | doi = 10.1016/S0167-7799(00)89014-9 }}</ref>

In 1877, German physiologist [[Wilhelm Kühne]] (1837–1900) first used the term ''[[wiktionary:enzyme|enzyme]]'', which comes {{ety|grc|''[[wikt:ένζυμο|ἔνζυμον]]'' (énzymon)|[[Bread#Leavening|leavened]], in yeast}}, to describe this process.<ref>Kühne coined the word "enzyme" in: {{cite journal | vauthors = Kühne W | year = 1877 | url = https://books.google.com/books?id=jzdMAAAAYAAJ&pg=PA190 | language = de | title = Über das Verhalten verschiedener organisirter und sog. ungeformter Fermente | trans-title = On the behavior of various organized and so-called unformed ferments | journal = Verhandlungen des Naturhistorisch-medicinischen Vereins zu Heidelberg | series = new series | volume = 1 | issue = 3 | pages = 190–193 }} Relevant passage on page 190: ''"Um Missverständnissen vorzubeugen und lästige Umschreibungen zu vermeiden schlägt Vortragender vor, die ungeformten oder nicht organisirten Fermente, deren Wirkung ohne Anwesenheit von Organismen und ausserhalb derselben erfolgen kann, als ''Enzyme'' zu bezeichnen."'' (Translation: In order to obviate misunderstandings and avoid cumbersome periphrases, [the author, a university lecturer] suggests designating as "enzymes" the unformed or not organized ferments, whose action can occur without the presence of organisms and outside of the same.)</ref> The word ''enzyme'' was used later to refer to nonliving substances such as [[pepsin]], and the word ''ferment'' was used to refer to chemical activity produced by living organisms.<ref>{{cite book | veditors = Heilbron JL | title = The Oxford Companion to the History of Modern Science | vauthors = Holmes FL | chapter = Enzymes | page = 270 | chapter-url = https://books.google.com/books?id=abqjP-_KfzkC&q=history+of+enzymes+ferment+living+organisms&pg=PA270 | publisher = Oxford University Press | location = Oxford | year = 2003 | isbn = 9780199743766 }}</ref>

[[Image:Eduardbuchner.jpg|alt=Photograph of Eduard Buchner.|thumb|left|Eduard Buchner]]

[[Eduard Buchner]] submitted his first paper on the study of yeast extracts in 1897. In a series of experiments at the [[Humboldt University of Berlin|University of Berlin]], he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture.<ref name="urlEduard Buchner – Biographical">{{cite web | url = https://nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-bio.html | title = Eduard Buchner | work = Nobel Laureate Biography | publisher = Nobelprize.org | access-date = 23 February 2015 }}</ref> He named the enzyme that brought about the fermentation of sucrose "[[zymase]]".<ref name="urlEduard Buchner – Nobel Lecture: Cell-Free Fermentation">{{cite web | url = https://nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-lecture.html | title = Eduard Buchner – Nobel Lecture: Cell-Free Fermentation | year = 1907 | work = Nobelprize.org | access-date = 23 February 2015 }}</ref> In 1907, he received the [[Nobel Prize in Chemistry]] for "his discovery of cell-free fermentation". Following Buchner's example, enzymes are usually named according to the reaction they carry out: the suffix ''[[-ase]]'' is combined with the name of the [[substrate (biochemistry)|substrate]] (e.g., [[lactase]] is the enzyme that cleaves [[lactose]]) or to the type of reaction (e.g., [[DNA polymerase]] forms DNA polymers).<ref>The naming of enzymes by adding the suffix "-ase" to the substrate on which the enzyme acts, has been traced to French scientist [[Émile Duclaux]] (1840–1904), who intended to honor the discoverers of [[diastase]] – the first enzyme to be isolated – by introducing this practice in his book {{cite book | author = Duclaux E | title = Traité de microbiologie: Diastases, toxines et venins | language = fr | trans-title = Microbiology Treatise: diastases, toxins and venoms | year = 1899 | publisher = Masson and Co | location = Paris, France | url = https://books.google.com/books?id=Kp9EAAAAQAAJ }} See Chapter 1, especially page 9.</ref>

The biochemical identity of enzymes was still unknown in the early 1900s. Many scientists observed that enzymatic activity was associated with proteins, but others (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.<ref name = "Willstätter_1927">{{cite journal| vauthors = Willstätter R | title = Faraday lecture. Problems and methods in enzyme research | journal = Journal of the Chemical Society (Resumed) | date = 1927 | pages = 1359–1381 |  doi = 10.1039/JR9270001359 }} quoted in {{cite journal | vauthors = Blow D | title = So do we understand how enzymes work? | journal = Structure | volume = 8 | issue = 4 | pages = R77–R81 | date = April 2000 | pmid = 10801479 | doi = 10.1016/S0969-2126(00)00125-8 | doi-access = free }}</ref> In 1926, [[James B. Sumner]] showed that the enzyme [[urease]] was a pure protein and crystallized it; he did likewise for the enzyme [[catalase]] in 1937. The conclusion that pure proteins can be enzymes was definitively demonstrated by [[John Howard Northrop]] and [[Wendell Meredith Stanley]], who worked on the digestive enzymes [[pepsin]] (1930), [[trypsin]] and [[chymotrypsin]]. These three scientists were awarded the 1946 Nobel Prize in Chemistry.<ref name="urlThe Nobel Prize in Chemistry 1946">{{cite web | url = https://nobelprize.org/nobel_prizes/chemistry/laureates/1946/ | title = Nobel Prizes and Laureates: The Nobel Prize in Chemistry 1946 | work = Nobelprize.org | access-date = 23 February 2015 }}</ref>

The 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 | vauthors = Blake CC, Koenig DF, Mair GA, North AC, Phillips DC, Sarma VR | title = Structure of hen egg-white lysozyme. A three-dimensional Fourier synthesis at 2 Angstrom resolution | journal = Nature | volume = 206 | issue = 4986 | pages = 757–761 | date = May 1965 | pmid = 5891407 | doi = 10.1038/206757a0 | s2cid = 4161467 | bibcode = 1965Natur.206..757B }}</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.<ref name="pmid10390620">{{cite journal | vauthors = Johnson LN, Petsko GA | title = David Phillips and the origin of structural enzymology | journal = Trends in Biochemical Sciences | volume = 24 | issue = 7 | pages = 287–289 | date = July 1999 | pmid = 10390620 | doi = 10.1016/S0968-0004(99)01423-1 }}</ref>

== Classification and nomenclature ==
Enzymes can be classified by two main criteria: either [[Protein primary structure|amino acid sequence]] similarity (and thus evolutionary relationship) or enzymatic activity.

'''Enzyme activity'''. An enzyme's name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in ''-ase''.<ref name="Stryer_2002" />{{rp|8.1.3}} Examples are [[lactase]], [[alcohol dehydrogenase]] and [[DNA polymerase]]. Different enzymes that catalyze the same chemical reaction are called [[isozyme]]s.<ref name="Stryer_2002" />{{rp|10.3}}

The [[International Union of Biochemistry and Molecular Biology]] have developed a [[nomenclature]] for enzymes, the [[Enzyme Commission number|EC numbers (for "Enzyme Commission")]]. Each enzyme is described by "EC" followed by a sequence of four numbers which represent the hierarchy of enzymatic activity (from very general to very specific). That is, the first number broadly classifies the enzyme based on its mechanism while the other digits add more and more specificity.<ref name="moss">{{cite web | vauthors = Moss GP |title=Recommendations of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology on the Nomenclature and Classification of Enzymes by the Reactions they Catalyse |url=https://www.qmul.ac.uk/sbcs/iubmb/enzyme/ |website=International Union of Biochemistry and Molecular Biology |access-date=28 August 2021}}</ref>

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.
*EC 7, [[Translocase]]s: catalyze the movement of ions or molecules across membranes, or their separation within membranes.

These sections are subdivided by other features such as the substrate, products, and [[chemical mechanism]]. An enzyme is fully specified by four numerical designations. For example, [[hexokinase]] (EC 2.7.1.1) is a transferase (EC 2) that adds a phosphate group (EC 2.7) to a hexose sugar, a molecule containing an alcohol group (EC 2.7.1).<ref>{{cite web | title = EC 2.7.1.1 | url = http://www.chem.qmul.ac.uk/iubmb/enzyme/EC2/7/1/1.html | author = Nomenclature Committee | work = International Union of Biochemistry and Molecular Biology (NC-IUBMB) | publisher = School of Biological and Chemical Sciences, Queen Mary, University of London | access-date = 6 March 2015 | archive-url = https://web.archive.org/web/20141201224835/http://www.chem.qmul.ac.uk/iubmb/enzyme/EC2/7/1/1.html | archive-date = 1 December 2014 | url-status = dead}}</ref>

'''Sequence similarity'''. EC categories do '''not''' reflect sequence similarity. For instance, two ligases of the same EC number that catalyze exactly the same reaction can have completely different sequences. Independent of their function, enzymes, like any other proteins, have been classified by their sequence similarity into numerous families. These families have been documented in dozens of different protein and protein family databases such as [[Pfam]].<ref>{{cite book | vauthors = Mulder NJ | chapter = Protein Family Databases|date=2007-09-28 |title =eLS|pages=a0003058.pub2|place=Chichester, UK|publisher=John Wiley & Sons, Ltd|language=en|doi=10.1002/9780470015902.a0003058.pub2|isbn=978-0-470-01617-6 }}</ref>

'''Non-homologous isofunctional enzymes'''. Unrelated enzymes that have the same enzymatic activity have been called ''non-homologous isofunctional enzymes''.<ref>{{cite journal | vauthors = Omelchenko MV, Galperin MY, Wolf YI, Koonin EV | title = Non-homologous isofunctional enzymes: a systematic analysis of alternative solutions in enzyme evolution | journal = Biology Direct | volume = 5 | issue = 1 | article-number = 31 | date = April 2010 | pmid = 20433725 | pmc = 2876114 | doi = 10.1186/1745-6150-5-31 | doi-access = free }}</ref> [[Horizontal gene transfer]] may spread these genes to unrelated species, especially bacteria where they can replace endogenous genes of the same function, leading to hon-homologous gene displacement.

== Structure ==
[[File:Q10 graph c.svg|thumb|400px|Enzyme activity initially increases with temperature ([[Q10 (temperature coefficient)|Q10 coefficient]]) until the enzyme's structure unfolds ([[denaturation (biochemistry)|denaturation]]), leading to an optimal [[rate of reaction]] at an intermediate temperature.|alt=A graph showing that reaction rate increases exponentially with temperature until denaturation causes it to decrease again.]]

{{see also|Protein structure}}

Enzymes are generally [[globular protein]]s, acting alone or in larger [[protein complex|complexes]]. The sequence of the amino acids specifies the structure which in turn determines the catalytic activity of the enzyme.<ref>{{cite journal | vauthors = Anfinsen CB | title = Principles that govern the folding of protein chains | journal = Science | volume = 181 | issue = 4096 | pages = 223–230 | date = July 1973 | pmid = 4124164 | doi = 10.1126/science.181.4096.223 | bibcode = 1973Sci...181..223A }}</ref> Although structure determines function, a novel enzymatic activity cannot yet be predicted from structure alone.<ref>{{cite journal | vauthors = Dunaway-Mariano D | title = Enzyme function discovery | journal = Structure | volume = 16 | issue = 11 | pages = 1599–1600 | date = November 2008 | pmid = 19000810 | doi = 10.1016/j.str.2008.10.001 | doi-access = free }}</ref> Enzyme structures unfold ([[denaturation (biochemistry)|denature]]) when heated or exposed to chemical denaturants and this disruption to the structure typically causes a loss of activity.<ref>{{cite book | vauthors = Petsko GA, Ringe D | title = Protein structure and function | date = 2003 | publisher = New Science | location = London | isbn=978-1405119221 | chapter = Chapter 1: From sequence to structure | chapter-url = https://books.google.com/books?id=2yRDWkHhN9QC&q=Protein+Denaturation+unfold+loss+of+function&pg=PA27 | page = 27 }}</ref> Enzyme denaturation is normally linked to temperatures above a species' normal level; as a result, enzymes from bacteria living in volcanic environments such as [[hot spring]]s are prized by industrial users for their ability to function at high temperatures, allowing enzyme-catalysed reactions to be operated at a very high rate.

Enzymes are usually much larger than their substrates. Sizes range from just 62 amino acid residues, for the [[monomer]] of [[4-Oxalocrotonate tautomerase|4-oxalocrotonate tautomerase]],<ref>{{cite journal | vauthors = 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 = The Journal of Biological Chemistry | volume = 267 | issue = 25 | pages = 17716–17721 | date = September 1992 | pmid = 1339435 | doi = 10.1016/S0021-9258(19)37101-7 | doi-access = free }}</ref> to over 2,500 residues in the animal [[fatty acid synthase]].<ref>{{cite journal | vauthors = Smith S | title = The animal fatty acid synthase: one gene, one polypeptide, seven enzymes | journal = FASEB Journal | volume = 8 | issue = 15 | pages = 1248–1259 | date = December 1994 | pmid = 8001737 | doi = 10.1096/fasebj.8.15.8001737 | doi-access = free | s2cid = 22853095 }}</ref> Only a small portion of their structure (around 2–4 amino acids) is directly involved in catalysis: the catalytic site.<ref>{{cite web | url = http://www.ebi.ac.uk/thornton-srv/databases/CSA/ | title = The Catalytic Site Atlas | publisher = The European Bioinformatics Institute | access-date = 4 April 2007 | archive-date = 27 September 2018 | archive-url = https://web.archive.org/web/20180927214709/http://www.ebi.ac.uk/thornton-srv/databases/CSA/ | url-status = dead }}</ref> This catalytic site is located next to one or more [[binding site]]s where residues orient the substrates. The catalytic site and binding site together compose the enzyme's [[active site]]. The remaining majority of the enzyme structure serves to maintain the precise orientation and dynamics of the active site.<ref name = "Suzuki_2015_7">{{cite book | author = Suzuki H | title = How Enzymes Work: From Structure to Function | publisher = CRC Press | location = Boca Raton, FL | year = 2015 | isbn = 978-981-4463-92-8 | chapter = Chapter 7: Active Site Structure | pages = 117–140 }}</ref>

In some enzymes, no amino acids are directly involved in catalysis; instead, the enzyme contains sites to bind and orient catalytic [[cofactor (biochemistry)|cofactors]].<ref name="Suzuki_2015_7" /> Enzyme structures may also contain [[allosteric site]]s where the binding of a small molecule causes a [[conformational change]] that increases or decreases activity.<ref>{{cite book | author = Krauss G | title = Biochemistry of Signal Transduction and Regulation | date = 2003 | publisher = Wiley-VCH | location = Weinheim | isbn = 9783527605767 | edition = 3rd | pages = 89–114 | chapter = The Regulations of Enzyme Activity | chapter-url = https://books.google.com/books?id=iAvu2XRLnfYC&q=enzyme+metabolic+pathways+feedback+regulation&pg=PA91}}</ref>

A small number of [[Ribonucleic acid|RNA]]-based biological catalysts called [[ribozyme]]s exist, which again can act alone or in complex with proteins. The most common of these is the [[ribosome]] which is a complex of protein and catalytic RNA components.<ref name = "Stryer_2002"/>{{rp|2.2}}

== Mechanism ==
[[File:Enzyme structure.svg|thumb|400px|Organisation of [[protein structure|enzyme structure]] and [[lysozyme]] example. Binding sites in blue, catalytic site in red and [[peptidoglycan]] substrate in black. ({{PDB|9LYZ}})|alt=Lysozyme displayed as an opaque globular surface with a pronounced cleft which the substrate depicted as a stick diagram snuggly fits into.]]

=== Substrate binding ===
Enzymes must bind their substrates before they can catalyse any chemical reaction. Enzymes are usually very specific as to what [[substrate (biochemistry)|substrates]] they bind and then the chemical reaction catalysed. [[Chemical specificity|Specificity]] is achieved by binding pockets with complementary shape, charge and [[hydrophilic]]/[[hydrophobic]] characteristics to the substrates. Enzymes can therefore distinguish between very similar substrate molecules to be [[chemoselectivity|chemoselective]], [[regioselectivity|regioselective]] and [[stereospecificity|stereospecific]].<ref>{{cite journal | vauthors = Jaeger KE, Eggert T | title = Enantioselective biocatalysis optimized by directed evolution | journal = Current Opinion in Biotechnology | volume = 15 | issue = 4 | pages = 305–313 | date = August 2004 | pmid = 15358000 | doi = 10.1016/j.copbio.2004.06.007 }}</ref>

Some of the enzymes showing the highest specificity and accuracy are involved in the copying and [[Gene expression|expression]] of the [[genome]]. Some of these enzymes have "[[Proofreading (biology)|proof-reading]]" mechanisms. Here, an enzyme such as [[DNA polymerase]] catalyzes a reaction in a first step and then checks that the product is correct in a second step.<ref>{{cite journal | vauthors = Shevelev IV, Hübscher U | title = The 3' 5' exonucleases | journal = Nature Reviews. Molecular Cell Biology | volume = 3 | issue = 5 | pages = 364–376 | date = May 2002 | pmid = 11988770 | doi = 10.1038/nrm804 | s2cid = 31605786 }}</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 name = "Stryer_2002"/>{{rp|5.3.1}} Similar proofreading mechanisms are also found in [[RNA polymerase]],<ref>{{cite journal | vauthors = Zenkin N, Yuzenkova Y, Severinov K | title = Transcript-assisted transcriptional proofreading | journal = Science | volume = 313 | issue = 5786 | pages = 518–520 | date = July 2006 | pmid = 16873663 | doi = 10.1126/science.1127422 | s2cid = 40772789 | bibcode = 2006Sci...313..518Z }}</ref> [[aminoacyl tRNA synthetase]]s<ref>{{cite journal | vauthors = Ibba M, Soll D | title = Aminoacyl-tRNA synthesis | journal = Annual Review of Biochemistry | volume = 69 | pages = 617–650 | year = 2000 | pmid = 10966471 | doi = 10.1146/annurev.biochem.69.1.617 }}</ref> and [[ribosome]]s.<ref>{{cite journal | vauthors = Rodnina MV, Wintermeyer W | title = Fidelity of aminoacyl-tRNA selection on the ribosome: kinetic and structural mechanisms | journal = Annual Review of Biochemistry | volume = 70 | pages = 415–435 | year = 2001 | pmid = 11395413 | doi = 10.1146/annurev.biochem.70.1.415 }}</ref>

Conversely, some enzymes display [[enzyme promiscuity]], having broad specificity and acting on a range of different physiologically relevant substrates. Many enzymes possess small side activities which arose fortuitously (i.e. [[Neutral evolution|neutrally]]), which may be the starting point for the evolutionary selection of a new function.<ref name=Tawfik10>{{cite journal | vauthors = Khersonsky O, Tawfik DS | title = Enzyme promiscuity: a mechanistic and evolutionary perspective | journal = Annual Review of Biochemistry | volume = 79 | pages = 471–505 | year = 2010 | pmid = 20235827 | doi = 10.1146/annurev-biochem-030409-143718 }}</ref><ref>{{cite journal | vauthors = O'Brien PJ, Herschlag D | title = Catalytic promiscuity and the evolution of new enzymatic activities | journal = Chemistry & Biology | volume = 6 | issue = 4 | pages = R91–R105 | date = April 1999 | pmid = 10099128 | doi = 10.1016/S1074-5521(99)80033-7 | doi-access = free }}</ref>

[[File:Hexokinase induced fit.svg|alt=Hexokinase displayed as an opaque surface with a pronounced open binding cleft next to unbound substrate (top) and the same enzyme with more closed cleft that surrounds the bound substrate (bottom)|thumb|400px|Enzyme changes shape by induced fit upon substrate binding to form enzyme-substrate complex. [[Hexokinase]] has a large induced fit motion that closes over the substrates [[adenosine triphosphate]] and [[xylose]]. Binding sites in blue, substrates in black and [[magnesium|Mg<sup>2+</sup>]] cofactor in yellow. ({{PDB|2E2N}}, {{PDB2|2E2Q}})]]

==== "Lock and key" model ====
To explain the observed specificity of enzymes, in 1894 [[Hermann Emil Fischer|Emil Fischer]] proposed that both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another.<ref>{{cite journal | vauthors = Fischer E | year = 1894 | title = Einfluss der Configuration auf die Wirkung der Enzyme | language = de | trans-title = Influence of configuration on the action of enzymes | journal=Berichte der Deutschen Chemischen Gesellschaft zu Berlin | volume = 27 | issue = 3 | pages = 2985–93 | url = https://gallica.bnf.fr/ark:/12148/bpt6k90736r/f364.chemindefer|doi=10.1002/cber.18940270364 }} From page 2992: ''"Um ein Bild zu gebrauchen, will ich sagen, dass Enzym und Glucosid wie Schloss und Schlüssel zu einander passen müssen, um eine chemische Wirkung auf einander ausüben zu können."'' (To use an image, I will say that an enzyme and a glucoside [i.e., glucose derivative] must fit like a lock and key, in order to be able to exert a chemical effect on each other.)</ref> This is often referred to as "the lock and key" model.<ref name="Stryer_2002" />{{rp|8.3.2}} This early model explains enzyme specificity, but fails to explain the stabilization of the transition state that enzymes achieve.<ref name="Cooper_2000">{{cite book | author = Cooper GM | title = The Cell: a Molecular Approach | date = 2000 | publisher = ASM Press | location = Washington (DC ) | isbn = 0-87893-106-6 | edition = 2nd | chapter = Chapter 2.2: The Central Role of Enzymes as Biological Catalysts | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK9921/ | url-access = registration | url = https://archive.org/details/cell00geof }}</ref>

==== Induced fit model ====
In 1958, [[Daniel E. Koshland, Jr.|Daniel Koshland]] suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continuously reshaped by interactions with the substrate as the substrate interacts with the enzyme.<ref>{{cite journal | vauthors = Koshland DE | title = Application of a Theory of Enzyme Specificity to Protein Synthesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 44 | issue = 2 | pages = 98–104 | date = February 1958 | pmid = 16590179 | pmc = 335371 | doi = 10.1073/pnas.44.2.98 | doi-access = free | bibcode = 1958PNAS...44...98K }}</ref> As a result, the substrate does not simply bind to a rigid active site; the amino acid [[Side chain|side-chains]] that make up the active site are molded 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 | vauthors = Vasella A, Davies GJ, Böhm M | title = Glycosidase mechanisms | journal = Current Opinion in Chemical Biology | volume = 6 | issue = 5 | pages = 619–629 | date = October 2002 | pmid = 12413546 | doi = 10.1016/S1367-5931(02)00380-0 }}</ref> The active site continues to change until the substrate is completely bound, at which point the final shape and charge distribution is determined.<ref>{{cite book | vauthors = Boyer R | title = Concepts in Biochemistry | edition = 2nd | publisher = John Wiley & Sons, Inc. | location = New York, Chichester, Weinheim, Brisbane, Singapore, Toronto. | isbn = 0-470-00379-0 | pages=137–8 | chapter = Chapter 6: Enzymes I, Reactions, Kinetics, and Inhibition | year = 2002 | oclc = 51720783 }}</ref>
Induced fit may enhance the fidelity of molecular recognition in the presence of competition and noise via the [[conformational proofreading]] mechanism.<ref>{{cite journal | vauthors = Savir Y, Tlusty T | title = Conformational proofreading: the impact of conformational changes on the specificity of molecular recognition | journal = PLOS ONE | volume = 2 | issue = 5 | pages = e468 | date = May 2007 | pmid = 17520027 | pmc = 1868595 | doi = 10.1371/journal.pone.0000468 | veditors = Scalas E | doi-access = free | bibcode = 2007PLoSO...2..468S }}</ref>

=== Catalysis ===

{{See also|Enzyme catalysis|Transition state theory}}

Enzymes can accelerate reactions in several ways, all of which lower the [[activation energy]] (ΔG<sup>‡</sup>, [[Gibbs free energy]])<ref name="Fersht_1985">{{cite book | author = Fersht A | title = Enzyme Structure and Mechanism | publisher = W.H. Freeman | location = San Francisco | year = 1985 | pages = 50–2 | isbn = 978-0-7167-1615-0}}</ref>
# By stabilizing the transition state:
#* Creating an environment with a charge distribution complementary to that of the transition state to lower its energy<ref>{{cite journal | vauthors = Warshel A, Sharma PK, Kato M, Xiang Y, Liu H, Olsson MH | title = Electrostatic basis for enzyme catalysis | journal = Chemical Reviews | volume = 106 | issue = 8 | pages = 3210–3235 | date = August 2006 | pmid = 16895325 | doi = 10.1021/cr0503106 }}</ref>
# By providing an alternative reaction pathway:
#* Temporarily reacting with the substrate, forming a covalent intermediate to provide a lower energy transition state<ref>{{cite book | vauthors = Cox MM, Nelson DL | title = Lehninger Principles of Biochemistry | date = 2013 | publisher = W.H. Freeman | location = New York, N.Y. | isbn = 978-1464109621 | edition = 6th | chapter = Chapter 6.2: How enzymes work | page = 195 }}</ref>
# By destabilizing the substrate ground state:
#* Distorting bound substrate(s) into their transition state form to reduce the energy required to reach the transition state<ref name=PMID12947189>{{cite journal | vauthors = Benkovic SJ, Hammes-Schiffer S | title = A perspective on enzyme catalysis | journal = Science | volume = 301 | issue = 5637 | pages = 1196–1202 | date = August 2003 | pmid = 12947189 | doi = 10.1126/science.1085515 | s2cid = 7899320 | bibcode = 2003Sci...301.1196B }}</ref>
#* By orienting the substrates into a productive arrangement to reduce the reaction [[entropy]] change<ref>{{cite book | author = Jencks WP | title = Catalysis in Chemistry and Enzymology | publisher = Dover | location = Mineola, N.Y | year = 1987 | isbn = 978-0-486-65460-7 }}</ref> (the contribution of this mechanism to catalysis is relatively small)<ref>{{cite journal | vauthors = Villa J, Strajbl M, Glennon TM, Sham YY, Chu ZT, Warshel A | title = How important are entropic contributions to enzyme catalysis? | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 22 | pages = 11899–11904 | date = October 2000 | pmid = 11050223 | pmc = 17266 | doi = 10.1073/pnas.97.22.11899 | doi-access = free | bibcode = 2000PNAS...9711899V }}</ref>
Enzymes may use several of these mechanisms simultaneously. For example, [[protease]]s such as [[trypsin]] perform covalent catalysis using a [[catalytic triad]], stabilize charge build-up on the transition states using an [[oxyanion hole]], complete [[hydrolysis]] using an oriented water substrate.<ref>{{cite journal | vauthors = Polgár L | title = The catalytic triad of serine peptidases | journal = Cellular and Molecular Life Sciences | volume = 62 | issue = 19–20 | pages = 2161–2172 | date = October 2005 | pmid = 16003488 | doi = 10.1007/s00018-005-5160-x | s2cid = 3343824 | pmc = 11139141 }}</ref>

=== Dynamics ===

{{See also|Protein dynamics}}

Enzymes are not rigid, static structures; instead they have complex internal dynamic motions – that is, movements of parts of the enzyme's structure such as individual amino acid residues, groups of residues forming a [[turn (biochemistry)|protein loop]] or unit of [[protein secondary structure|secondary structure]], or even an entire [[protein domain]]. These motions give rise to a [[conformational ensemble]] of slightly different structures that interconvert with one another at [[thermodynamic equilibrium|equilibrium]]. Different states within this ensemble may be associated with different aspects of an enzyme's function. For example, different conformations of the enzyme [[dihydrofolate reductase]] are associated with the substrate binding, catalysis, cofactor release, and product release steps of the catalytic cycle,<ref>{{cite journal | vauthors = Ramanathan A, Savol A, Burger V, Chennubhotla CS, Agarwal PK | title = Protein conformational populations and functionally relevant substates | journal = Accounts of Chemical Research | volume = 47 | issue = 1 | pages = 149–156 | date = January 2014 | pmid = 23988159 | doi = 10.1021/ar400084s | osti = 1565147 }}</ref> consistent with [[catalytic resonance theory]]. The transitions between the different conformations during the catalytic cycle involve internal [[Viscoelasticity|viscoelastic]] motion that is facilitated by high-[[Strain (mechanics)|strain]] regions where amino acids are rearranged.<ref>{{Cite journal |last1=Weinreb |first1=Eyal |last2=McBride |first2=John M. |last3=Siek |first3=Marta |last4=Rougemont |first4=Jacques |last5=Renault |first5=Renaud |last6=Peleg |first6=Yoav |last7=Unger |first7=Tamar |last8=Albeck |first8=Shira |last9=Fridmann-Sirkis |first9=Yael |last10=Lushchekina |first10=Sofya |last11=Sussman |first11=Joel L. |last12=Grzybowski |first12=Bartosz A. |last13=Zocchi |first13=Giovanni |last14=Eckmann |first14=Jean-Pierre |last15=Moses |first15=Elisha |date=2025-03-28 |title=Enzymes as viscoelastic catalytic machines |url=https://www.nature.com/articles/s41567-025-02825-9 |journal=Nature Physics |volume=21 |issue=5 |language=en |pages=787–798 |doi=10.1038/s41567-025-02825-9 |bibcode=2025NatPh..21..787W |issn=1745-2481|url-access=subscription }}</ref>

=== Substrate presentation ===
[[Substrate presentation]] is a process where the enzyme is sequestered away from its substrate. Enzymes can be sequestered to the plasma membrane away from a substrate in the nucleus or cytosol.<ref>{{cite journal | vauthors = Agrawal D, Budakoti M, Kumar V | title = Strategies and tools for the biotechnological valorization of glycerol to 1, 3-propanediol: Challenges, recent advancements and future outlook | journal = Biotechnology Advances | volume = 66 | article-number = 108177 | date = September 2023 | pmid = 37209955 | doi = 10.1016/j.biotechadv.2023.108177 | hdl = 1826/19759 | hdl-access = free }}</ref> Or within the membrane, an enzyme can be sequestered into lipid rafts away from its substrate in the disordered region. When the enzyme is released it mixes with its substrate. Alternatively, the enzyme can be sequestered near its substrate to activate the enzyme. For example, the enzyme can be soluble and upon activation bind to a lipid in the plasma membrane and then act upon molecules in the plasma membrane.<ref>{{cite journal | vauthors = Selvy PE, Lavieri RR, Lindsley CW, Brown HA | title = Phospholipase D: enzymology, functionality, and chemical modulation | journal = Chemical Reviews | volume = 111 | issue = 10 | pages = 6064–6119 | date = October 2011 | pmid = 21936578 | pmc = 3233269 | doi = 10.1021/cr200296t }}</ref>

=== Allosteric modulation ===
{{main|Allosteric regulation}}

Allosteric sites are pockets on the enzyme, distinct from the active site, that bind to molecules in the cellular environment. These molecules then cause a change in the conformation or dynamics of the enzyme that is transduced to the active site and thus affects the reaction rate of the enzyme.<ref>{{cite journal | vauthors = Tsai CJ, Del Sol A, Nussinov R | title = Protein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms | journal = Molecular BioSystems | volume = 5 | issue = 3 | pages = 207–216 | date = March 2009 | pmid = 19225609 | pmc = 2898650 | doi = 10.1039/b819720b }}</ref> In this way, allosteric interactions can either inhibit or activate enzymes. Allosteric interactions with metabolites upstream or downstream in an enzyme's metabolic pathway cause [[feedback]] regulation, altering the activity of the enzyme according to the [[Flux (metabolism)|flux]] through the rest of the pathway.<ref>{{cite journal | vauthors = Changeux JP, Edelstein SJ | title = Allosteric mechanisms of signal transduction | journal = Science | volume = 308 | issue = 5727 | pages = 1424–1428 | date = June 2005 | pmid = 15933191 | doi = 10.1126/science.1108595 | s2cid = 10621930 | bibcode = 2005Sci...308.1424C }}</ref>

==Cofactors==
[[File:Transketolase + TPP.png|thumb|400px|alt=Thiamine pyrophosphate displayed as an opaque globular surface with an open binding cleft where the substrate and cofactor both depicted as stick diagrams fit into.|Chemical structure for [[thiamine pyrophosphate]] and protein structure of [[transketolase]]. Thiamine pyrophosphate cofactor in yellow and [[xylulose 5-phosphate]] substrate in black. ({{PDB|4KXV}})]]

{{main|Cofactor (biochemistry)}}

Some enzymes do not need additional components to show full activity. Others require non-protein molecules called cofactors to be bound for activity.<ref>{{cite web | url = http://www.chem.qmul.ac.uk/iupac/bioinorg/CD.html#34 | title = Glossary of Terms Used in Bioinorganic Chemistry: Cofactor | access-date = 30 October 2007 | vauthors = de Bolster MW | year = 1997 | publisher = International Union of Pure and Applied Chemistry | archive-url = https://web.archive.org/web/20170121172848/http://www.chem.qmul.ac.uk/iupac/bioinorg/CD.html#34 | archive-date = 21 January 2017 | url-status = dead}}</ref> Cofactors can be either [[inorganic]] (e.g., metal [[ion]]s and [[iron–sulfur cluster]]s) or [[organic compound]]s (e.g., [[flavin group|flavin]] and [[heme]]). These cofactors serve many purposes; for instance, metal ions can help in stabilizing nucleophilic species within the active site.<ref>{{Cite book |title=Fundamentals of Biochemistry | vauthors = Voet D, Voet J, Pratt C |publisher=John Wiley & Sons, Inc. |year=2016 |isbn=978-1-118-91840-1 |location=Hoboken, New Jersey |pages=336}}</ref> Organic cofactors can be either [[coenzyme]]s, which are released from the enzyme's active site during the reaction, or [[prosthetic groups]], which are tightly bound to an enzyme. Organic prosthetic groups can be covalently bound (e.g., [[biotin]] in enzymes such as [[pyruvate carboxylase]]).<ref name="pmid10470036">{{cite journal | vauthors = Chapman-Smith A, Cronan JE | title = The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity | journal = Trends in Biochemical Sciences | volume = 24 | issue = 9 | pages = 359–363 | date = September 1999 | pmid = 10470036 | doi = 10.1016/s0968-0004(99)01438-3 }}</ref>

An example of an enzyme that contains a cofactor is [[carbonic anhydrase]], which uses a zinc cofactor bound as part of its active site.<ref>{{cite journal | vauthors = Fisher Z, Hernandez Prada JA, Tu C, Duda D, Yoshioka C, An H, Govindasamy L, Silverman DN, McKenna R | title = Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II | journal = Biochemistry | volume = 44 | issue = 4 | pages = 1097–1105 | date = February 2005 | pmid = 15667203 | doi = 10.1021/bi0480279 }}</ref> These tightly bound ions or molecules are usually found in the active site and are involved in catalysis.<ref name = "Stryer_2002"/>{{rp|8.1.1}} For example, flavin and heme cofactors are often involved in [[redox]] reactions.<ref name = "Stryer_2002"/>{{rp|17}}

Enzymes that require a cofactor but do not have one bound are called ''apoenzymes'' or ''apoproteins''. An enzyme together with the cofactor(s) required for activity is called a ''holoenzyme'' (or haloenzyme). The term ''holoenzyme'' can also be applied to enzymes that contain multiple protein subunits, such as the [[DNA polymerase]]s; here the holoenzyme is the complete complex containing all the subunits needed for activity.<ref name = "Stryer_2002"/>{{rp|8.1.1}}

===Coenzymes===

Coenzymes are small organic molecules that can be loosely or tightly bound to an enzyme. Coenzymes transport chemical groups from one enzyme to another.<ref name = "Wagner_1975">{{cite book | author = Wagner AL | title = Vitamins and Coenzymes | publisher = Krieger Pub Co | year = 1975 | isbn = 0-88275-258-8}}</ref> Examples include [[Nicotinamide adenine dinucleotide|NADH]], [[Nicotinamide adenine dinucleotide phosphate|NADPH]] and [[adenosine triphosphate]] (ATP). Some coenzymes, such as [[flavin mononucleotide]] (FMN), [[flavin adenine dinucleotide]] (FAD), [[thiamine pyrophosphate]] (TPP), and [[tetrahydrofolate]] (THF), are derived from [[vitamin]]s. These coenzymes cannot be synthesized by the body ''[[De novo synthesis|de novo]]'' and closely related compounds (vitamins) 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 phosphate group, carried by [[adenosine triphosphate]] 
* the acetyl group, carried by [[coenzyme A]] 
* formyl, methenyl or methyl groups, carried by [[folic acid]] and 
* the methyl group, carried by [[S-adenosylmethionine]]<ref name = "Wagner_1975"/>
 
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 1000 enzymes are known to use the coenzyme NADH.<ref>{{cite web | url = https://www.brenda-enzymes.org | title = BRENDA The Comprehensive Enzyme Information System | publisher = Technische Universität Braunschweig | access-date = 23 February 2015 }}</ref>

Coenzymes are usually continuously 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]]. This continuous regeneration means that small amounts of coenzymes can be used very intensively. For example, the human body turns over its own weight in ATP each day.<ref>{{cite journal | vauthors = Törnroth-Horsefield S, Neutze R | title = Opening and closing the metabolite gate | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 50 | pages = 19565–19566 | date = December 2008 | pmid = 19073922 | pmc = 2604989 | doi = 10.1073/pnas.0810654106 | doi-access = free | bibcode = 2008PNAS..10519565T }}</ref>

==Thermodynamics==
[[File:Enzyme catalysis energy levels 2.svg|thumb|400px|alt=A two dimensional plot of reaction coordinate (x-axis) vs. energy (y-axis) for catalyzed and uncatalyzed reactions. The energy of the system steadily increases from reactants (x = 0) until a maximum is reached at the transition state (x = 0.5), and steadily decreases to the products (x = 1). However, in an enzyme catalysed reaction, binding generates an enzyme-substrate complex (with slightly reduced energy) then increases up to a transition state with a smaller maximum than the uncatalysed reaction.|The energies of the stages of a [[chemical reaction]]. Uncatalysed (dashed line), substrates need a lot of [[activation energy]] to reach a [[transition state]], which then decays into lower-energy products. When enzyme catalysed (solid line), the enzyme binds the substrates (ES), then stabilizes the transition state (ES<sup>‡</sup>) to reduce the activation energy required to produce products (EP) which are finally released.]]

{{main |Activation energy|Thermodynamic equilibrium|Chemical equilibrium}}

As with all catalysts, enzymes do not alter the position of the chemical equilibrium of the reaction. In the presence of an enzyme, the reaction runs in the same direction as it would without the enzyme, just more quickly.<ref name = "Stryer_2002"/>{{rp|8.2.3}} For example, [[carbonic anhydrase]] catalyzes its reaction in either direction depending on the concentration of its reactants:<ref>{{cite book |vauthors=McArdle WD, Katch F, Katch VL | title = Essentials of Exercise Physiology | date = 2006 | publisher = Lippincott Williams & Wilkins | location = Baltimore, Maryland | isbn = 978-0781749916 | pages = 312–3 | edition = 3rd | chapter = Chapter 9: The Pulmonary System and Exercise | chapter-url = https://books.google.com/books?id=L4aZIDbmV3oC&q=carbonic+anhydrase+lung+tissue+low+high+carbon+dioxide+equilibrium&pg=PA313}}</ref>

{{NumBlk|:| <chem>CO2{} + H2O ->[\text{Carbonic anhydrase}] H2CO3</chem> (in [[Tissue (biology)|tissues]]; high CO<sub>2</sub> concentration)|{{EquationRef|1}}}}

{{NumBlk|:| <chem>CO2{} + H2O <-[\text{Carbonic anhydrase}] H2CO3</chem> (in [[lung]]s; low CO<sub>2</sub> concentration)|{{EquationRef|2}}}}

The rate of a reaction is dependent on the [[activation energy]] needed to form the [[transition state]] which then decays into products. Enzymes increase reaction rates by lowering the energy of the transition state. First, binding forms a low energy enzyme-substrate complex (ES). Second, the enzyme stabilises the transition state such that it requires less energy to achieve compared to the uncatalyzed reaction (ES<sup>‡</sup>). Finally the enzyme-product complex (EP) dissociates to release the products.<ref name = "Stryer_2002"/>{{rp|8.3}}

Enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive" a thermodynamically unfavourable one so that the combined energy of the products is lower than the substrates. For example, the hydrolysis of [[Adenosine triphosphate|ATP]] is often used to drive other chemical reactions.<ref name="Nicholls">{{cite book |vauthors=Ferguson SJ, Nicholls D, Ferguson S | title = Bioenergetics 3 | publisher = Academic | location = San Diego | year = 2002 | isbn = 0-12-518121-3 | edition = 3rd}}</ref>

==Kinetics==

 {{multiple image
 | direction = vertical
 | width = 325
 | footer =

 | image1 = Enzyme mechanism 2.svg
 | alt1 = Schematic reaction diagrams for uncatalzyed (Substrate to Product) and catalyzed (Enzyme + Substrate to Enzyme/Substrate complex to Enzyme + Product)
 | caption1 = A chemical reaction mechanism with or without [[enzyme catalysis]]. The enzyme (E) binds [[substrate (chemistry)|substrate]] (S) to produce [[product (chemistry)|product]] (P).

 | image2 = Michaelis Menten curve 2.svg
 | alt2 = A two dimensional plot of substrate concentration (x axis) vs. reaction rate (y axis). The shape of the curve is hyperbolic. The rate of the reaction is zero at zero concentration of substrate and the rate asymptotically reaches a maximum at high substrate concentration.
 | caption2 = [[Michaelis–Menten kinetics|Saturation curve]] for an enzyme reaction showing the relation between the substrate concentration and reaction rate.
 }}

{{main|Enzyme kinetics}}

Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products.<ref>{{Cite book|title=Enzyme kinetics : principles and methods | vauthors = Bisswanger H | year = 2017 |isbn=9783527806461|edition= Third, enlarged and improved |location=Weinheim, Germany | publisher = Wiley-VCH |oclc=992976641}}</ref> The rate data used in kinetic analyses are commonly obtained from [[enzyme assay]]s. In 1913 [[Leonor Michaelis]] and [[Maud Leonora Menten]] proposed a quantitative theory of enzyme kinetics, which is referred to as [[Michaelis–Menten kinetics]].<ref>{{cite journal | vauthors = Michaelis L, Menten M | year = 1913 | title = Die Kinetik der Invertinwirkung | journal = Biochem. Z. | volume = 49 | pages = 333–369 | language = de | trans-title = The Kinetics of Invertase Action }}; {{cite journal | vauthors = Michaelis L, Menten ML, Johnson KA, Goody RS | title = The original Michaelis constant: translation of the 1913 Michaelis-Menten paper | journal = Biochemistry | volume = 50 | issue = 39 | pages = 8264–8269 | date = October 2011 | pmid = 21888353 | pmc = 3381512 | doi = 10.1021/bi201284u }}</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. This work was further developed by [[George Edward Briggs|G.&nbsp;E. Briggs]] and [[J.&nbsp;B.&nbsp;S. Haldane]], who derived kinetic equations that are still widely used today.<ref>{{cite journal | vauthors = Briggs GE, Haldane JB | title = A Note on the Kinetics of Enzyme Action | journal = The Biochemical Journal | volume = 19 | issue = 2 | pages = 338–339 | year = 1925 | pmid = 16743508 | pmc = 1259181 | doi = 10.1042/bj0190338 }}</ref>

Enzyme rates depend on [[Solution (chemistry)|solution]] conditions and substrate [[concentration]]. To find the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is seen. This is shown in the saturation curve on the right. Saturation happens because, as substrate concentration increases, more and more of the free enzyme is converted into the substrate-bound ES complex. At the maximum reaction rate (''V''<sub>max</sub>) of the enzyme, all the enzyme active sites are bound to substrate, and the amount of ES complex is the same as the total amount of enzyme.<ref name = "Stryer_2002"/>{{rp|8.4}}

''V''<sub>max</sub> is only one of several important kinetic parameters. 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 reaction rate; generally, each enzyme has a characteristic ''K''<sub>M</sub> for a given substrate. Another useful constant is ''k''<sub>cat</sub>, also called the ''turnover number'', which is the number of substrate molecules handled by one active site per second.<ref name = "Stryer_2002"/>{{rp|8.4}}

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 up to and including the first irreversible step. 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]], [[β-lactamase]], and [[superoxide dismutase]].<ref name = "Stryer_2002"/>{{rp|8.4.2}} The turnover of such enzymes can reach several million reactions per second.<ref name = "Stryer_2002"/>{{rp|9.2}} But most enzymes are far from perfect: the average values of <math>k_{\rm cat}/K_{\rm m}</math> and <math>k_{\rm cat}</math> are about <math> 10^5 {\rm s}^{-1}{\rm M}^{-1}</math> and <math>10 {\rm s}^{-1}</math>, respectively.<ref name="Bar-Even_2011">{{cite journal | vauthors = Bar-Even A, Noor E, Savir Y, Liebermeister W, Davidi D, Tawfik DS, Milo R | title = The moderately efficient enzyme: evolutionary and physicochemical trends shaping enzyme parameters | journal = Biochemistry | volume = 50 | issue = 21 | pages = 4402–4410 | date = May 2011 | pmid = 21506553 | doi = 10.1021/bi2002289 }}</ref>

Michaelis–Menten kinetics relies on the [[law of mass action]], which is derived from the assumptions of free [[diffusion]] and thermodynamically driven random collision. Many biochemical or cellular processes deviate significantly from these conditions, because of [[macromolecular crowding]] and constrained molecular movement.<ref>{{cite journal | vauthors = Ellis RJ | title = Macromolecular crowding: obvious but underappreciated | journal = Trends in Biochemical Sciences | volume = 26 | issue = 10 | pages = 597–604 | date = October 2001 | pmid = 11590012 | doi = 10.1016/S0968-0004(01)01938-7 }}</ref> More recent, complex extensions of the model attempt to correct for these effects.<ref>{{cite journal | vauthors = Kopelman R | title = Fractal reaction kinetics | journal = Science | volume = 241 | issue = 4873 | pages = 1620–1626 | date = September 1988 | pmid = 17820893 | doi = 10.1126/science.241.4873.1620 | s2cid = 23465446 | bibcode = 1988Sci...241.1620K }}</ref>

==Inhibition==

 {{multiple image
 | direction = vertical
 | width = 400
 | footer =

 | image1 = DHFR methotrexate inhibitor.svg
 | alt1 =

 | image2 = Methotrexate vs folate 2.svg
 | alt2 = Two dimensional representations of the chemical structure of folic acid and methotrexate highlighting the differences between these two substances (amidation of pyrimidone and methylation of secondary amine).
 | caption2 = The coenzyme [[folic acid]] (left) and the anti-cancer drug [[methotrexate]] (right) are very similar in structure (differences show in green). As a result, methotrexate is a competitive inhibitor of many enzymes that use folates.
 }}

{{main|Enzyme inhibitor}}

Enzyme reaction rates can be decreased by various types of enzyme inhibitors.<ref name = "Cornish-Bowden_2004">{{cite book | author = Cornish-Bowden A | title = Fundamentals of Enzyme Kinetics | date = 2004 | publisher = Portland Press | location = London | isbn = 1-85578-158-1 | edition = 3 }}</ref>{{rp|73–74}}

===Types of inhibition===

====Competitive====
A [[competitive inhibitor]] and substrate cannot bind to the enzyme at the same time.<ref name = "Price_1979">{{cite journal | vauthors = Price NC | year = 1979 | title = What is meant by 'competitive inhibition'? | journal = Trends in Biochemical Sciences | volume = 4 | issue=11 | pages = N272–N273 | doi = 10.1016/0968-0004(79)90205-6 }}</ref> Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, the drug [[methotrexate]] is a competitive inhibitor of the enzyme [[dihydrofolate reductase]], which catalyzes the reduction of [[folic acid|dihydrofolate]] to tetrahydrofolate.<ref name="Goodsell 340–341">{{cite journal | vauthors = Goodsell DS | title = The molecular perspective: methotrexate | journal = The Oncologist | volume = 4 | issue = 4 | pages = 340–341 | date = 1999-08-01 | pmid = 10476546 | doi = 10.1634/theoncologist.4-4-340 | doi-access = free }}</ref> The similarity between the structures of dihydrofolate and this drug are shown in the accompanying figure. This type of inhibition can be overcome with high substrate concentration. In some cases, the inhibitor can bind to a site other than the binding-site of the usual substrate and exert an [[#Allosteric modulation|allosteric effect]] to change the shape of the usual binding-site.<ref>{{cite journal | vauthors = Wu P, Clausen MH, Nielsen TE | title = Allosteric small-molecule kinase inhibitors | journal = Pharmacology & Therapeutics | volume = 156 | pages = 59–68 | date = December 2015 | pmid = 26478442 | doi = 10.1016/j.pharmthera.2015.10.002 | s2cid = 1550698 | url = https://backend.orbit.dtu.dk/ws/files/129911346/PT_Revised_Main_Manuscript_with_embedded_figures.pdf }}</ref>

====Non-competitive====
A [[non-competitive inhibition|non-competitive inhibitor]] binds to a site other than where the substrate binds. The substrate still binds with its usual affinity and hence K<sub>m</sub> remains the same. However the inhibitor reduces the catalytic efficiency of the enzyme so that V<sub>max</sub> is reduced. In contrast to competitive inhibition, non-competitive inhibition cannot be overcome with high substrate concentration.<ref name = "Cornish-Bowden_2004"/>{{rp|76–78}}

====Uncompetitive====
An [[uncompetitive inhibitor]] cannot bind to the free enzyme, only to the enzyme-substrate complex; hence, these types of inhibitors are most effective at high substrate concentration. In the presence of the inhibitor, the enzyme-substrate complex is inactive.<ref name = "Cornish-Bowden_2004"/>{{rp|78}} This type of inhibition is rare.<ref>{{cite journal | vauthors = Cornish-Bowden A | title = Why is uncompetitive inhibition so rare? A possible explanation, with implications for the design of drugs and pesticides | journal = FEBS Letters | volume = 203 | issue = 1 | pages = 3–6 | date = July 1986 | pmid = 3720956 | doi = 10.1016/0014-5793(86)81424-7 | bibcode = 1986FEBSL.203....3C | s2cid = 45356060 | author-link1 = Athel Cornish-Bowden }}</ref>

====Mixed====
A [[mixed inhibition|mixed inhibitor]] binds to an allosteric site and the binding of the substrate and the inhibitor affect each other. The enzyme's function is reduced but not eliminated when bound to the inhibitor. This type of inhibitor does not follow the Michaelis–Menten equation.<ref name = "Cornish-Bowden_2004"/>{{rp|76–78}}

====Irreversible====
An [[irreversible inhibitor]] permanently inactivates the enzyme, usually by forming a [[covalent bond]] to the protein.<ref>{{cite journal | vauthors = Strelow JM | title = A Perspective on the Kinetics of Covalent and Irreversible Inhibition | journal = SLAS Discovery | volume = 22 | issue = 1 | pages = 3–20 | date = January 2017 | pmid = 27703080 | doi = 10.1177/1087057116671509 | doi-access = free }}</ref> [[Penicillin]]<ref>{{cite journal | vauthors = Fisher JF, Meroueh SO, Mobashery S | title = Bacterial resistance to beta-lactam antibiotics: compelling opportunism, compelling opportunity | journal = Chemical Reviews | volume = 105 | issue = 2 | pages = 395–424 | date = February 2005 | pmid = 15700950 | doi = 10.1021/cr030102i }}</ref> and [[aspirin]]<ref name="Johnson">{{cite journal | vauthors = Johnson DS, Weerapana E, Cravatt BF | title = Strategies for discovering and derisking covalent, irreversible enzyme inhibitors | journal = Future Medicinal Chemistry | volume = 2 | issue = 6 | pages = 949–964 | date = June 2010 | pmid = 20640225 | pmc = 2904065 | doi = 10.4155/fmc.10.21 }}</ref> are common drugs that act in this manner.

===Functions of inhibitors===

In many organisms, inhibitors may act as part of a [[feedback]] mechanism. If an enzyme produces too much of one substance in the organism, that substance may act as an inhibitor for the enzyme at the beginning of the pathway that produces it, causing production of the substance to slow down or stop when there is sufficient amount. This is a form of [[negative feedback]]. Major metabolic pathways such as the [[citric acid cycle]] make use of this mechanism.<ref name = "Stryer_2002" />{{rp|17.2.2}}

Since inhibitors modulate the function of enzymes they are often used as drugs. Many such drugs are reversible competitive inhibitors that resemble the enzyme's native substrate, similar to [[methotrexate]] above; other well-known examples include [[statin]]s used to treat high [[cholesterol]],<ref name="Endo1992">{{cite journal | vauthors = Endo A | title = The discovery and development of HMG-CoA reductase inhibitors | journal = Journal of Lipid Research | volume = 33 | issue = 11 | pages = 1569–1582 | date = November 1992 | pmid = 1464741 | doi = 10.1016/S0022-2275(20)41379-3 | doi-access = free }}</ref> and [[protease inhibitors]] used to treat [[retroviral]] infections such as [[HIV]].<ref>{{cite journal | vauthors = Wlodawer A, Vondrasek J | title = Inhibitors of HIV-1 protease: a major success of structure-assisted drug design | journal = Annual Review of Biophysics and Biomolecular Structure | volume = 27 | pages = 249–284 | date = 1998 | pmid = 9646869 | doi = 10.1146/annurev.biophys.27.1.249 | s2cid = 10205781 }}</ref> A common example of an irreversible inhibitor that is used as a drug is [[aspirin]], which inhibits the [[Cyclooxygenase|COX-1]] and [[Cyclooxygenase|COX-2]] enzymes that produce the [[inflammation]] messenger [[prostaglandin]].<ref name="Johnson" /> Other enzyme inhibitors are poisons. For example, 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 | vauthors = Yoshikawa S, Caughey WS | title = Infrared evidence of cyanide binding to iron and copper sites in bovine heart cytochrome c oxidase. Implications regarding oxygen reduction | journal = The Journal of Biological Chemistry | volume = 265 | issue = 14 | pages = 7945–7958 | date = May 1990 | pmid = 2159465 | doi = 10.1016/S0021-9258(19)39023-4 | doi-access = free }}</ref>

== Factors affecting enzyme activity ==
As enzymes are made up of proteins, their actions are sensitive to change in many physio chemical factors such as pH, temperature, substrate concentration, etc.

The following table shows pH optima for various enzymes.<ref>{{Cite book|title=Fundamentals of biochemistry| vauthors = Jain JL | publisher = S. Chand and Co |isbn=8121903432|location=New Delhi|oclc=818809626|date = May 1999}}</ref>
{| class="wikitable sortable"
|+
!Enzyme
!Optimum pH
!pH description
|-
|Pepsin
|1.5–1.6
|Highly acidic
|-
|Invertase
|4.5
|Acidic
|-
|Lipase (stomach)
|4.0–5.0
|Acidic
|-
|Lipase (castor oil)
|4.7
|Acidic
|-
|Lipase (pancreas)
|8.0
|Alkaline
|-
|Amylase (malt)
|4.6–5.2
|Acidic
|-
|Amylase (pancreas)
|6.7–7.0
|Acidic-neutral
|-
|Cellobiase
|5.0
|Acidic
|-
|Maltase
|6.1–6.8
|Acidic
|-
|Sucrase
|6.2
|Acidic
|-
|Catalase
|7.0
|Neutral
|-
|Urease
|7.0
|Neutral
|-
|Cholinesterase
|7.0
|Neutral
|-
|Ribonuclease
|7.0–7.5
|Neutral
|-
|Fumarase
|7.8
|Alkaline
|-
|Trypsin
|7.8–8.7
|Alkaline
|-
|Adenosine triphosphate
|9.0
|Alkaline
|-
|Arginase
|10.0
|Highly alkaline
|}

== Biological function ==

Enzymes serve a wide variety of [[function (biology)|functions]] inside living organisms. They are indispensable for [[signal transduction]] and cell regulation, often via [[kinase]]s and [[phosphatase]]s.<ref>{{cite journal | vauthors = Hunter T | title = Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling | journal = Cell | volume = 80 | issue = 2 | pages = 225–236 | date = January 1995 | pmid = 7834742 | doi = 10.1016/0092-8674(95)90405-0 | s2cid = 13999125 | doi-access = free }}</ref> They also generate movement, with [[myosin]] hydrolyzing [[adenosine triphosphate]] (ATP) to generate [[muscle contraction]], and also transport cargo around the cell as part of the [[cytoskeleton]].<ref>{{cite journal | vauthors = Berg JS, Powell BC, Cheney RE | title = A millennial myosin census | journal = Molecular Biology of the Cell | volume = 12 | issue = 4 | pages = 780–794 | date = April 2001 | pmid = 11294886 | pmc = 32266 | doi = 10.1091/mbc.12.4.780 }}</ref> Other [[ATPase]]s 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 [[fireflies]].<ref>{{cite journal | vauthors = Meighen EA | title = Molecular biology of bacterial bioluminescence | journal = Microbiological Reviews | volume = 55 | issue = 1 | pages = 123–142 | date = March 1991 | pmid = 2030669 | pmc = 372803 | doi = 10.1128/MMBR.55.1.123-142.1991 }}</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]].<ref name="pmid12370077">{{cite journal | vauthors = De Clercq E | title = Highlights in the development of new antiviral agents | journal = Mini Reviews in Medicinal Chemistry | volume = 2 | issue = 2 | pages = 163–175 | date = April 2002 | pmid = 12370077 | doi = 10.2174/1389557024605474 }}</ref>

An important function of enzymes is in the [[digestive systems]] of animals. Enzymes such as [[amylase]]s and [[protease]]s break down large molecules ([[starch]] or [[protein]]s, respectively) into smaller ones, so they can be absorbed by the intestines. Starch molecules, for example, are too large to be absorbed from the intestine, but enzymes hydrolyze the starch chains into smaller molecules such as [[maltose]] and eventually [[glucose]], which can then be absorbed. Different enzymes digest different food substances. In [[ruminant]]s, which have [[herbivorous]] diets, microorganisms in the gut produce another enzyme, [[cellulase]], to break down the cellulose cell walls of plant fiber.<ref>{{cite journal | vauthors = Mackie RI, White BA | title = Recent advances in rumen microbial ecology and metabolism: potential impact on nutrient output | journal = Journal of Dairy Science | volume = 73 | issue = 10 | pages = 2971–2995 | date = October 1990 | pmid = 2178174 | doi = 10.3168/jds.S0022-0302(90)78986-2 | doi-access = free }}</ref>

===Metabolism===

[[Image:Glycolysis metabolic pathway.svg|thumb|upright=2|alt=Schematic diagram of the glycolytic metabolic pathway starting with glucose and ending with pyruvate via several intermediate chemicals. Each step in the pathway is catalyzed by a unique enzyme.|The [[metabolic pathway]] of [[glycolysis]] releases energy by converting [[glucose]] to [[pyruvate]] via a series of intermediate metabolites. Each chemical modification (red box) is performed by a different enzyme.]]

Several enzymes can work together in a specific order, creating [[metabolic pathway]]s.<ref name = "Stryer_2002" />{{rp|30.1}} 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 catalyze the same reaction in parallel; this can allow more complex regulation: with, for example, a low constant activity provided by one enzyme but an inducible high activity from a second enzyme.<ref name="Rouzer_2009">{{cite journal | vauthors = Rouzer CA, Marnett LJ | title = Cyclooxygenases: structural and functional insights | journal = Journal of Lipid Research | volume = 50 | issue = Suppl | pages = S29–S34 | date = April 2009 | pmid = 18952571 | pmc = 2674713 | doi = 10.1194/jlr.R800042-JLR200  |doi-access=free }}</ref>

Enzymes determine what steps occur in these pathways. Without enzymes, metabolism would neither progress through the same steps and could not be regulated to serve the needs of the cell. Most central metabolic pathways are regulated at a few steps, typically through enzymes whose activity involves the phosphorylation by ATP. Because this reaction releases so much energy, other reactions that are [[endothermic|thermodynamically unfavorable]] can be coupled to ATP hydrolysis, driving the overall series of linked metabolic reactions.<ref name = "Stryer_2002" />{{rp|30.1}}

=== Control of activity ===

There are five main ways that enzyme activity is controlled in the cell.<ref name = "Stryer_2002" />{{rp|30.1.1}}

====Regulation====
Enzymes can be either [[enzyme activator|activated]] or [[enzyme inhibitor|inhibited]] by other molecules. 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.<ref name = "Suzuki_2015_8"/>{{rp|141–48}} 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.<ref name = "Suzuki_2015_8"/>{{rp|141}}

====Post-translational modification====
Examples of [[post-translational modification]] include [[phosphorylation]], [[myristoylation]] and [[glycosylation]].<ref name = "Suzuki_2015_8">{{cite book | author = Suzuki H | title = How Enzymes Work: From Structure to Function | publisher = CRC Press | location = Boca Raton, FL | year = 2015 | isbn = 978-981-4463-92-8 | chapter = Chapter 8: Control of Enzyme Activity | pages = 141–69 }}</ref>{{rp|149–69}} 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 name = "Doble_2003">{{cite journal | vauthors = Doble BW, Woodgett JR | title = GSK-3: tricks of the trade for a multi-tasking kinase | journal = Journal of Cell Science | volume = 116 | issue = Pt 7 | pages = 1175–1186 | date = April 2003 | pmid = 12615961 | pmc = 3006448 | doi = 10.1242/jcs.00384 }}</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]]<ref name = "Suzuki_2015_8"/>{{rp|149–53}} or proenzyme.

====Quantity====
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]]. 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.<ref name="pmid8452343">{{cite journal | vauthors = Bennett PM, Chopra I | title = Molecular basis of beta-lactamase induction in bacteria | journal = Antimicrobial Agents and Chemotherapy | volume = 37 | issue = 2 | pages = 153–158 | date = February 1993 | pmid = 8452343 | pmc = 187630 | doi = 10.1128/aac.37.2.153 }}</ref> Another example comes from 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.<ref name = "Skett_Gibson_2001">{{cite book |vauthors=Skett P, Gibson GG | title = Introduction to Drug Metabolism | date = 2001 | publisher = Nelson Thornes Publishers | location = Cheltenham, UK | isbn = 978-0748760114 | pages = 87–118 | edition = 3 | chapter = Chapter 3: Induction and Inhibition of Drug Metabolism }}</ref> Enzyme levels can also be regulated by changing the rate of enzyme [[catabolism|degradation]].<ref name="Stryer_2002" />{{rp|30.1.1}} The opposite of enzyme induction is [[enzyme repression]].

====Subcellular distribution====
Enzymes can be compartmentalized, with different metabolic pathways occurring in different [[cellular compartment]]s. For example, [[fatty acid]]s are synthesized by one set of enzymes in the [[cytosol]], [[endoplasmic reticulum]] and [[golgi apparatus|Golgi]] and used by a different set of enzymes as a source of energy in the [[mitochondrion]], through [[β-oxidation]].<ref>{{cite journal | vauthors = Faergeman NJ, Knudsen J | title = Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling | journal = The Biochemical Journal | volume = 323 | issue = Pt 1 | pages = 1–12 | date = April 1997 | pmid = 9173866 | pmc = 1218279 | doi = 10.1042/bj3230001 }}</ref> In addition, [[protein targeting|trafficking]] of the enzyme to different compartments may change the degree of [[protonation]] (e.g., the neutral [[cytoplasm]] and the acidic [[lysosome]]) or oxidative state (e.g., oxidizing [[periplasm]] or reducing [[cytoplasm]]) which in turn affects enzyme activity.<ref name = "Suzuki_2015_4">{{cite book | author = Suzuki H | title = How Enzymes Work: From Structure to Function | publisher = CRC Press | location = Boca Raton, FL | year = 2015 | isbn = 978-981-4463-92-8 | chapter = Chapter 4: Effect of pH, Temperature, and High Pressure on Enzymatic Activity | pages = 53–74 }}</ref> In contrast to partitioning into membrane bound organelles, enzyme subcellular localisation may also be altered through polymerisation of enzymes into macromolecular cytoplasmic filaments.<ref>{{cite journal | vauthors = Noree C, Sato BK, Broyer RM, Wilhelm JE | title = Identification of novel filament-forming proteins in Saccharomyces cerevisiae and Drosophila melanogaster | journal = The Journal of Cell Biology | volume = 190 | issue = 4 | pages = 541–551 | date = August 2010 | pmid = 20713603 | pmc = 2928026 | doi = 10.1083/jcb.201003001 }}</ref><ref>{{cite journal | vauthors = Aughey GN, Liu JL | title = Metabolic regulation via enzyme filamentation | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 51 | issue = 4 | pages = 282–293 | date = 2015 | pmid = 27098510 | pmc = 4915340 | doi = 10.3109/10409238.2016.1172555 }}</ref>

====Organ specialization====
In [[multicellular]] [[eukaryote]]s, cells in different [[organ (anatomy)|organs]] and [[tissue (biology)|tissues]] have different patterns of [[gene expression]] and therefore have different sets of enzymes (known as [[isozyme]]s) available for metabolic reactions. This provides a mechanism for regulating the overall metabolism of the organism. For example, [[hexokinase]], the first enzyme in the [[glycolysis]] pathway, has a specialized form called [[glucokinase]] expressed in the liver and [[pancreas]] that has a lower [[affinity (pharmacology)|affinity]] for glucose yet is more sensitive to glucose concentration.<ref>{{cite journal | vauthors = Kamata K, Mitsuya M, Nishimura T, Eiki J, Nagata Y | title = Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase | journal = Structure | volume = 12 | issue = 3 | pages = 429–438 | date = March 2004 | pmid = 15016359 | doi = 10.1016/j.str.2004.02.005 | doi-access = free }}</ref> This enzyme is involved in sensing [[blood sugar]] and regulating insulin production.<ref>{{cite journal | vauthors = Froguel P, Zouali H, Vionnet N, Velho G, Vaxillaire M, Sun F, Lesage S, Stoffel M, Takeda J, Passa P | title = Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus | journal = The New England Journal of Medicine | volume = 328 | issue = 10 | pages = 697–702 | date = March 1993 | pmid = 8433729 | doi = 10.1056/NEJM199303113281005 | doi-access = free }}</ref>

=== Involvement in disease ===
[[File:Phenylalanine hydroxylase mutations.svg|thumb|upright=2|alt= Ribbon diagram of phenylalanine hydroxylase with bound cofactor, coenzyme and substrate|In [[phenylalanine hydroxylase]] over 300 different mutations throughout the structure cause [[phenylketonuria]]. [[Phenylalanine]] substrate and [[tetrahydrobiopterin]] coenzyme in black, and [[Iron|Fe<sup>2+</sup>]] cofactor in yellow. ({{PDB|1KW0}})]]
[[File:Autosomal recessive inheritance for affected enzyme.png|thumb|upright=1.4|Hereditary defects in enzymes are generally inherited in an [[autosomal inheritance|autosomal]] fashion because there are more non-X chromosomes than X-chromosomes, and a [[recessive inheritance|recessive]] fashion because the enzymes from the unaffected genes are generally sufficient to prevent symptoms in carriers.]]
{{see also|Genetic disorder}}

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 malfunction of just one type of enzyme out of the thousands of types present in the human body can be fatal. An example of a fatal genetic disease due to enzyme insufficiency is [[Tay–Sachs disease]], in which patients lack the enzyme [[hexosaminidase]].<ref>{{cite journal | vauthors = Okada S, O'Brien JS | title = Tay-Sachs disease: generalized absence of a beta-D-N-acetylhexosaminidase component | journal = Science | volume = 165 | issue = 3894 | pages = 698–700 | date = August 1969 | pmid = 5793973 | doi = 10.1126/science.165.3894.698 | s2cid = 8473726 | bibcode = 1969Sci...165..698O }}</ref><ref>{{cite web | title = Learning About Tay–Sachs Disease | url = http://www.genome.gov/10001220 | publisher = U.S. National Human Genome Research Institute | access-date = 1 March 2015 }}</ref>

One example of enzyme deficiency is the most common type of [[phenylketonuria]]. Many different single amino acid mutations in the enzyme [[phenylalanine hydroxylase]], which catalyzes the first step in the degradation of [[phenylalanine]], result in build-up of phenylalanine and related products. Some mutations are in the active site, directly disrupting binding and catalysis, but many are far from the active site and reduce activity by destabilising the protein structure, or affecting correct oligomerisation.<ref name=pmid10527663>{{cite journal | vauthors = Erlandsen H, Stevens RC | title = The structural basis of phenylketonuria | journal = Molecular Genetics and Metabolism | volume = 68 | issue = 2 | pages = 103–125 | date = October 1999 | pmid = 10527663 | doi = 10.1006/mgme.1999.2922 }}</ref><ref>{{cite journal | vauthors = Flatmark T, Stevens RC | title = Structural Insight into the Aromatic Amino Acid Hydroxylases and Their Disease-Related Mutant Forms | journal = Chemical Reviews | volume = 99 | issue = 8 | pages = 2137–2160 | date = August 1999 | pmid = 11849022 | doi = 10.1021/cr980450y }}</ref> This can lead to [[intellectual disability]] if the disease is untreated.<ref>{{cite book | title = Genes and Disease [Internet] | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK22253/ | chapter = Phenylketonuria | publisher = National Center for Biotechnology Information (US) | location = Bethesda (MD) | year = 1998–2015 }}</ref> Another example is [[pseudocholinesterase deficiency]], in which the body's ability to break down choline ester drugs is impaired.<ref>{{cite web | title = Pseudocholinesterase deficiency | url = https://medlineplus.gov/genetics/condition/pseudocholinesterase-deficiency/ | publisher = U.S. National Library of Medicine | access-date = 5 September 2013 }}</ref>
Oral administration of enzymes can be used to treat some functional enzyme deficiencies, such as [[pancreatic insufficiency]]<ref>{{cite journal | vauthors = Fieker A, Philpott J, Armand M | title = Enzyme replacement therapy for pancreatic insufficiency: present and future | journal = Clinical and Experimental Gastroenterology | volume = 4 | pages = 55–73 | date = 2011 | pmid = 21753892 | pmc = 3132852 | doi = 10.2147/CEG.S17634 | doi-access = free }}</ref> and [[lactose intolerance]].<ref>{{cite journal | vauthors = Misselwitz B, Pohl D, Frühauf H, Fried M, Vavricka SR, Fox M | title = Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment | journal = United European Gastroenterology Journal | volume = 1 | issue = 3 | pages = 151–159 | date = June 2013 | pmid = 24917953 | pmc = 4040760 | doi = 10.1177/2050640613484463 }}</ref>

Another way enzyme malfunctions can cause disease comes from [[germline mutation]]s in genes coding for [[DNA repair]] enzymes. Defects in these enzymes cause cancer because cells are less able to repair mutations in their [[genome]]s. This causes a slow accumulation of mutations and results in the [[carcinogenesis|development of cancers]]. An example of such a hereditary [[cancer syndrome]] is [[xeroderma pigmentosum]], which causes the development of [[skin cancer]]s in response to even minimal exposure to [[ultraviolet light]].<ref>{{cite journal | vauthors = Cleaver JE | title = Defective repair replication of DNA in xeroderma pigmentosum | journal = Nature | volume = 218 | issue = 5142 | pages = 652–656 | date = May 1968 | pmid = 5655953 | doi = 10.1038/218652a0 | s2cid = 4171859 | bibcode = 1968Natur.218..652C }}</ref><ref name="Andrews">{{cite book | vauthors = James WD, Elston D, Berger TG | title = Andrews' Diseases of the Skin: Clinical Dermatology | date = 2011 | publisher = Saunders/ Elsevier | location = London | isbn = 978-1437703146 | edition = 11th | page = 567 }}</ref>

== Evolution ==
Similar to any other protein, enzymes change over time through [[mutation]]s and sequence divergence. Given their central role in [[metabolism]], enzyme evolution plays a critical role in [[adaptation]]. A key question is therefore whether and how enzymes can change their enzymatic activities alongside. It is generally accepted that many new enzyme activities have evolved through [[gene duplication]] and mutation of the duplicate copies although evolution can also happen without duplication. One example of an enzyme that has changed its activity is the ancestor of [[methionyl aminopeptidase]] (MAP) and creatine amidinohydrolase ([[creatinase]]) which are clearly homologous but catalyze very different reactions (MAP removes the amino-terminal [[methionine]] in new proteins while creatinase hydrolyses [[creatine]] to [[sarcosine]] and [[urea]]). In addition, MAP is metal-ion dependent while creatinase is not, hence this property was also lost over time.<ref>{{cite journal | vauthors = Murzin AG | title = Can homologous proteins evolve different enzymatic activities? | journal = Trends in Biochemical Sciences | volume = 18 | issue = 11 | pages = 403–405 | date = November 1993 | pmid = 8291080 | doi = 10.1016/0968-0004(93)90132-7 }}</ref> Small changes of enzymatic activity are extremely common among enzymes. In particular, substrate binding specificity (see above) can easily and quickly change with single amino acid changes in their substrate binding pockets. This is frequently seen in the main enzyme classes such as [[kinase]]s.<ref>{{cite journal | vauthors = Ochoa D, Bradley D, Beltrao P | title = Evolution, dynamics and dysregulation of kinase signalling | journal = Current Opinion in Structural Biology | volume = 48 | pages = 133–140 | date = February 2018 | pmid = 29316484 | doi = 10.1016/j.sbi.2017.12.008 }}</ref>

Artificial (in vitro) evolution is now commonly used to modify enzyme activity or specificity for industrial applications (see below).

== Industrial applications ==
{{main|Industrial enzymes}}

Enzymes are used in the [[chemical industry]] and other industrial applications when extremely specific catalysts are required. Enzymes in general are limited in the number of reactions they have evolved to catalyze and also by their lack of stability in [[organic solvent]]s and at high temperatures. As a consequence, [[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 | vauthors = Renugopalakrishnan V, Garduño-Juárez R, Narasimhan G, Verma CS, Wei X, Li P | title = Rational design of thermally stable proteins: relevance to bionanotechnology | journal = Journal of Nanoscience and Nanotechnology | volume = 5 | issue = 11 | pages = 1759–1767 | date = November 2005 | pmid = 16433409 | doi = 10.1166/jnn.2005.441 }}</ref><ref>{{cite journal | vauthors = Hult K, Berglund P | title = Engineered enzymes for improved organic synthesis | journal = Current Opinion in Biotechnology | volume = 14 | issue = 4 | pages = 395–400 | date = August 2003 | pmid = 12943848 | doi = 10.1016/S0958-1669(03)00095-8 }}</ref> These efforts have begun to be successful, and a few enzymes have now been designed "from scratch" to catalyze reactions that do not occur in nature.<ref>{{cite journal | vauthors = Jiang L, Althoff EA, Clemente FR, Doyle L, Röthlisberger D, Zanghellini A, Gallaher JL, Betker JL, Tanaka F, Barbas CF, Hilvert D, Houk KN, Stoddard BL, Baker D | title = De novo computational design of retro-aldol enzymes | journal = Science | volume = 319 | issue = 5868 | pages = 1387–1391 | date = March 2008 | pmid = 18323453 | pmc = 3431203 | doi = 10.1126/science.1152692 | bibcode = 2008Sci...319.1387J }}</ref>

{| class="wikitable"
|- style="text-align:center;"
! style="width:24%; "|Application
! style="width:38%; "|Enzymes used
! style="width:38%; "|Uses
|- valign="top"
| style="border-top:solid 3px #aaa;" rowspan="2"|'''[[Biofuel|Biofuel industry]]'''
| style="border-top:solid 3px #aaa;"|[[Cellulase]]s
| style="border-top:solid 3px #aaa;"|Break down cellulose into sugars that can be fermented to produce [[cellulosic ethanol]].<ref name="cheng">{{cite journal | vauthors = Sun Y, Cheng J | title = Hydrolysis of lignocellulosic materials for ethanol production: a review | journal = Bioresource Technology | volume = 83 | issue = 1 | pages = 1–11 | date = May 2002 | pmid = 12058826 | doi = 10.1016/S0960-8524(01)00212-7 | bibcode = 2002BiTec..83....1S }}</ref>
|- valign="top"
| [[Ligninase]]s
| Pretreatment of [[biomass]] for biofuel production.<ref name="cheng" />
|- valign="top"
| style="border-top:solid 3px #aaa;" rowspan="2"| '''[[Biological detergent]]'''
| style="border-top:solid 3px #aaa;"|[[Protease]]s, [[amylase]]s, [[lipase]]s
| style="border-top:solid 3px #aaa;"|Remove protein, starch, and fat or oil stains from laundry and dishware.<ref name="Kirk">{{cite journal | vauthors = Kirk O, Borchert TV, Fuglsang CC | title = Industrial enzyme applications | journal = Current Opinion in Biotechnology | volume = 13 | issue = 4 | pages = 345–351 | date = August 2002 | pmid = 12323357 | doi = 10.1016/S0958-1669(02)00328-2 }}</ref>
|- valign="top"
| [[Mannanase]]s
| Remove food stains from the common food additive [[guar gum]].<ref name="Kirk" />
|- valign="top"
| style="border-top:solid 3px #aaa;" rowspan="4"| '''[[Brewing|Brewing industry]]'''
| style="border-top:solid 3px #aaa;"|[[Amylase]], [[glucanase]]s, [[protease]]s
| style="border-top:solid 3px #aaa;"|Split polysaccharides and proteins in the [[malt]].<ref name="briggs">{{cite book | vauthors = Briggs DE | title = Malts and Malting | date = 1998 | publisher = Blackie Academic | location = London | isbn = 978-0412298004 | edition = 1st }}</ref>{{rp|150–9}}
|- valign="top"
| [[Betaglucanase]]s
| Improve the [[wort]] and beer filtration characteristics.<ref name="briggs" />{{rp|545}}
|- valign="top"
| [[Amyloglucosidase]] and [[pullulanase]]s
| Make low-calorie [[beer]] and adjust fermentability.<ref name="briggs" />{{rp|575}}
|- valign="top"
| [[Acetolactate decarboxylase]] (ALDC)
| Increase fermentation efficiency by reducing [[diacetyl]] formation.<ref>{{cite journal | vauthors = Dulieu C, Moll M, Boudrant J, Poncelet D | title = Improved performances and control of beer fermentation using encapsulated alpha-acetolactate decarboxylase and modeling | journal = Biotechnology Progress | volume = 16 | issue = 6 | pages = 958–965 | year = 2000 | pmid = 11101321 | doi = 10.1021/bp000128k | s2cid = 25674881 | doi-access = free }}</ref>
|- valign="top"
| style="border-top:solid 3px #aaa;"|'''[[Cooking|Culinary uses]]'''
| style="border-top:solid 3px #aaa;"|[[Papain]]
| style="border-top:solid 3px #aaa;"|[[Tenderizer|Tenderize]] meat for cooking.<ref>{{cite book | vauthors = Tarté R | title = Ingredients in Meat Products Properties, Functionality and Applications | date = 2008 | publisher = Springer | location = New York | isbn = 978-0-387-71327-4 | pages = 177 }}</ref>
|- valign="top"
| style="border-top:solid 3px #aaa;" rowspan="2"| '''[[Dairy|Dairy industry]]'''
| style = "border-top:solid 3px #aaa;"|[[Chymosin|Rennin]]
| style="border-top:solid 3px #aaa;"|[[Hydrolyze]] protein in the manufacture of [[cheese]].<ref>{{cite web|url=http://www.gmo-compass.org/eng/database/enzymes/83.chymosin.html|access-date=1 March 2015|date=10 July 2010|title=Chymosin – GMO Database|work=GMO Compass|publisher=European Union|url-status=dead|archive-url=https://web.archive.org/web/20150326181805/http://www.gmo-compass.org/eng/database/enzymes/83.chymosin.html|archive-date=26 March 2015}}</ref>
|- valign="top"
| [[Lipase]]s
| Produce [[Camembert cheese]] and [[blue cheese]]s such as [[Roquefort]].<ref>{{cite journal | vauthors = Molimard P, Spinnler HE | title = Review: Compounds Involved in the Flavor of Surface Mold-Ripened Cheeses: Origins and Properties | journal = Journal of Dairy Science | date = February 1996 | volume = 79 | issue = 2 | pages = 169–184 | doi = 10.3168/jds.S0022-0302(96)76348-8| doi-access = free }}</ref>
|- valign="top"
| style="border-top:solid 3px #aaa;" rowspan="4"| '''[[Food processing]]'''
| style="border-top:solid 3px #aaa;"|[[Amylase]]s
| style="border-top:solid 3px #aaa;"|Produce sugars from [[starch]], such as in making [[high-fructose corn syrup]].<ref>{{cite journal | vauthors = Guzmán-Maldonado H, Paredes-López O | title = Amylolytic enzymes and products derived from starch: a review | journal = Critical Reviews in Food Science and Nutrition | volume = 35 | issue = 5 | pages = 373–403 | date = September 1995 | pmid = 8573280 | doi = 10.1080/10408399509527706 }}</ref>
|- valign="top"
| [[Protease]]s
| Lower the protein level of [[flour]], as in [[biscuit]]-making.<ref name="GMOdatabase" />
|- valign="top"
||[[Trypsin]]
|Manufacture [[hypoallergenic]] baby foods.<ref name="GMOdatabase">{{cite web | url = http://www.gmo-compass.org/eng/database/enzymes/94.protease.html | title = Protease – GMO Database | date = 10 July 2010 | work = GMO Compass | publisher = European Union | access-date = 28 February 2015 | url-status = dead | archive-url = https://web.archive.org/web/20150224164346/http://www.gmo-compass.org/eng/database/enzymes/94.protease.html | archive-date = 24 February 2015}}</ref>
|- valign="top"
| [[Cellulase]]s, [[pectinase]]s
| Clarify [[fruit juice]]s.<ref>{{cite journal | vauthors = Alkorta I, Garbisu C, Llama MJ, Serra JL | title = Industrial applications of pectic enzymes: a review | journal = Process Biochemistry | date = January 1998 | volume = 33 | issue = 1 | pages = 21–28 | doi = 10.1016/S0032-9592(97)00046-0 }}</ref>
|- valign="top"
| style="border-top:solid 3px #aaa;"|'''[[Molecular biology]]'''
| style="border-top:solid 3px #aaa;"|[[Nuclease]]s, [[DNA ligase]] and [[polymerase]]s
| style="border-top:solid 3px #aaa;"|Use [[restriction enzyme|restriction digestion]] and the [[polymerase chain reaction]] to create [[recombinant DNA]].<ref name="Stryer_2002" />{{rp|6.2}}
|- valign="top"
| style="border-top:solid 3px #aaa;"|'''[[Paper|Paper industry]]'''
| style="border-top:solid 3px #aaa;"|[[Xylanase]]s, [[hemicellulase]]s and [[lignin peroxidase]]s
| style="border-top:solid 3px #aaa;"|Remove [[lignin]] from [[kraft pulp]].<ref>{{cite journal | vauthors = Bajpai P | title = Application of enzymes in the pulp and paper industry | journal = Biotechnology Progress | volume = 15 | issue = 2 | pages = 147–157 | date = March 1999 | pmid = 10194388 | doi = 10.1021/bp990013k | s2cid = 26080240 }}</ref>
|- valign="top"
| style="border-top:solid 3px #aaa;"|'''[[Personal care]]'''
| style="border-top:solid 3px #aaa;"|[[Protease]]s
| style="border-top:solid 3px #aaa;"|Remove proteins on [[contact lens]]es to prevent infections.<ref>{{cite journal | vauthors = Begley CG, Paragina S, Sporn A | title = An analysis of contact lens enzyme cleaners | journal = Journal of the American Optometric Association | volume = 61 | issue = 3 | pages = 190–194 | date = March 1990 | pmid = 2186082 }}</ref>
|- valign="top"
| style="border-top:solid 3px #aaa;" rowspan="1"| '''[[Starch|Starch industry]]'''
| style="border-top:solid 3px #aaa;"| [[Amylase]]s
| style="border-top:solid 3px #aaa;"| Convert [[starch]] into [[glucose]] and various [[Inverted sugar syrup|syrups]].<ref>{{cite book | veditors = BeMiller JN, Whistler RL | title = Starch Chemistry and Technology | date = 2009 | publisher = Academic | location = London | isbn = 9780080926551 | edition= 3rd | vauthors = Farris PL | chapter = Economic Growth and Organization of the U.S. Starch Industry }}</ref>
|}

== See also ==
{{Portal|Biology|Food}}

* [[Industrial enzymes]]
* [[List of enzymes]]
* [[Molecular machine]]

=== Enzyme databases ===
* [[BRENDA]]
* [[ExPASy]]
* [[IntEnz]]
* [[KEGG]]
* [[MetaCyc]]

== References ==
{{reflist}}

== Further reading ==
{{Col-begin}}
{{Col-1-of-2}}

;General
* {{cite book | vauthors = Berg JM, Tymoczko JL, Stryer L | title = Biochemistry | date = 2002 | publisher = W. H. Freeman | location = New York, NY | isbn = 0-7167-3051-0 | edition = 5th | url = https://archive.org/details/biochemistrychap00jere | url-access = registration }}, A biochemistry textbook available free online through NCBI Bookshelf.{{Open access}}

;Etymology and history
* {{cite book | title = New Beer in an Old Bottle: Eduard Buchner and the Growth of Biochemical Knowledge | url = http://bip.cnrs-mrs.fr/bip10/buchner.htm | veditors = Cornish-Bowden A | publisher = Universitat de València | year = 1997 | isbn = 84-370-3328-4 | access-date = 27 June 2006 | archive-date = 13 December 2010 | archive-url = https://web.archive.org/web/20101213084345/http://bip.cnrs-mrs.fr/bip10/buchner.htm | url-status = dead }}, A history of early enzymology.

{{Col-2-of-2}}

;Enzyme structure and mechanism
* {{cite book | author = Suzuki H | title = How Enzymes Work: From Structure to Function | publisher = CRC Press | location = Boca Raton, FL | year = 2015 | isbn = 978-981-4463-92-8 }}

;Kinetics and inhibition
* {{cite book | vauthors = Cornish-Bowden A | title = Fundamentals of Enzyme Kinetics | date = 2012 | publisher = Wiley-VCH | location = Weinheim | isbn = 978-3527330744 | edition = 4th }}

{{Col-end}}

== External links ==
*{{Commons category-inline|Enzymes}}

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