{{short description|Large biological molecule that acts as a catalyst}}
{{Biochemistry sidebar/ja}}
[[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.]]
'''Enzymes''' ({{IPAc-en|ˈ|ɛ|n|z|aɪ|m|z}}) are [[protein]]s that act as biological [[catalyst]]s by accelerating [[chemical reactions]]. The [[molecules]] upon which enzymes may act are called [[substrate (chemistry)|substrates]], and the enzyme converts the substrates into different molecules known as [[product (chemistry)|products]]. Almost all [[metabolism|metabolic processes]] in the [[cell (biology)|cell]] need [[enzyme catalysis]] in order to occur at rates fast enough to sustain life. [[Metabolic pathway]]s depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of [[pseudoenzyme|pseudoenzyme analysis]] recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their [[amino acid]] sequences and unusual 'pseudocatalytic' properties.
Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are [[Ribozyme|catalytic RNA molecules]], called [[ribozymes]]. An enzyme's [[Chemical specificity|specificity]] comes from its unique [[tertiary structure|three-dimensional structure]].
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[[File:IUPAC definition for enzymes.png|thumb|right|550px|link=https://doi.org/10.1351/goldbook.E02159|IUPACによる酵素の定義]]
[[File:IUPAC definition for enzymes.png|thumb|right|550px|link=https://doi.org/10.1351/goldbook.E02159|IUPAC definition for enzymes]]
Like all catalysts, enzymes increase the [[reaction rate]] by lowering its [[activation energy]]. Some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is [[orotidine 5'-phosphate decarboxylase]], which allows a reaction that would otherwise take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, nor do they alter the [[Chemical equilibrium|equilibrium]] of a reaction. Enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules: [[Enzyme inhibitor|inhibitors]] are molecules that decrease enzyme activity, and [[enzyme activator|activators]] are molecules that increase activity. Many therapeutic [[drug]]s and [[poison]]s are enzyme inhibitors. An enzyme's activity decreases markedly outside its optimal [[temperature]] and [[pH]], and many enzymes are (permanently) [[Denaturation (biochemistry)|denatured]] when exposed to excessive heat, losing their structure and catalytic properties.
Some enzymes are used commercially, for example, in the synthesis of [[antibiotic]]s. Some household products use enzymes to speed up chemical reactions: enzymes in [[Detergent enzymes|biological washing powder]]s break down protein, starch or [[fat]] stains on clothes, and enzymes in [[papain|meat tenderizer]] break down proteins into smaller molecules, making the meat easier to chew.
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== 語源と歴史 ==
== Etymology and history ==
{{Anchor|Etymology and history}}
[[Image:Eduardbuchner.jpg|alt=Photograph of Eduard Buchner.|thumb|left|Eduard Buchner]]
[[Image:Eduardbuchner.jpg|alt=Photograph of Eduard Buchner.|thumb|left|Eduard Buchner]]
By the late 17th and early 18th centuries, the digestion of [[meat]] by stomach secretions 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.
French chemist [[Anselme Payen]] was the first to discover an enzyme, [[diastase]], in 1833. 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."
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.
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1897年に[[:en:Eduard Buchner|エドゥアルド・ブフナー]]が酵母エキスの研究に関する最初の論文を提出した。彼は[[:en:Humboldt University of Berlin|ベルリン大学]]での一連の実験において、混合物中に生きた酵母細胞が存在しなくても、酵母エキスによって砂糖が発酵することを発見した。彼はショ糖の発酵をもたらす酵素を「[[zymase/ja|ザイマーゼ]]」と名付けた。1907年、彼は「無細胞発酵の発見」により[[:en:Nobel Prize in Chemistry|ノーベル化学賞]]を受賞した。ブフナーの例に倣い、酵素は通常、それらが行う反応に従って命名される。接尾辞''[[-ase/ja|-ase]]''は[[substrate (biochemistry)/ja|基質]]の名前と組み合わされる（例えば、[[lactase/ja|ラクターゼ]]は[[lactose/ja|乳糖]]を切断する酵素である）、あるいは反応の種類に組み合わされる（例えば、[[DNA polymerase/ja|DNAポリメラーゼ]]はDNAポリマーを形成する）。
[[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. He named the enzyme that brought about the fermentation of sucrose "[[zymase]]". 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).
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酵素の生化学的な正体は、1900年代初頭にはまだ不明であった。多くの科学者は酵素活性がタンパク質と関連していることを観察していたが、他の科学者（ノーベル賞受賞者の[[:en:Richard Willstätter|リチャード・ウィルシュテッター]]など）は、タンパク質は真の酵素の単なるキャリアであり、タンパク質''それ自体''は触媒作用ができないと主張していた。1926年、[[:en:James B. Sumner|ジェームズ・B・サムナー]]は[[urease/ja|ウレアーゼ]]という酵素が純粋なタンパク質であることを示し、それを結晶化させた。1937年には[[catalase/ja|カタラーゼ]]という酵素も同様に結晶化させた。純粋なタンパク質が酵素になりうるという結論は、消化酵素[[pepsin/ja|ペプシン]]（1930年）、[[trypsin/ja|トリプシン]]、[[chymotrypsin/ja|キモトリプシン]]の研究を行った[[:en:John Howard Northrop|ジョン・ハワード・ノースロップ]]と[[:en:Wendell Meredith Stanley|ウェンデル・メレディス・スタンリー]]によって決定的に示された。これら3人の科学者は1946年にノーベル化学賞を受賞した。
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. 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.
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. 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.
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== 分類と命名法 ==
== Classification and nomenclature ==
{{Anchor|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''. Examples are [[lactase]], [[alcohol dehydrogenase]] and [[DNA polymerase]]. Different enzymes that catalyze the same chemical reaction are called [[isozyme]]s.
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[[:en:International Union of Biochemistry and Molecular Biology|国際生化学分子生物学連合]]は、酵素の[[:en:nomenclature|命名法]]である[[Enzyme Commission number/ja|EC番号（「酵素委員会」の意）]]を開発した。
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.
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).
'''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]].
'''Non-homologous isofunctional enzymes'''. Unrelated enzymes that have the same enzymatic activity have been called ''non-homologous isofunctional enzymes''. [[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.
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== 構造 ==
== Structure ==
{{Anchor|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.]]
[[File:Q10 graph c.svg|thumb|400px|酵素活性は、最初は温度とともに増加する（[[Q10 (temperature coefficient)/ja|Q10係数]]）が、酵素の構造がアンフォールディング（[[denaturation (biochemistry)/ja|変性]]）し、ある中間温度で最適な[[rate of reaction/ja|反応速度]]を示すようになる。|alt=反応速度が温度によって指数関数的に増加し、変性によって再び減少することを示すグラフ。]]
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. Although structure determines function, a novel enzymatic activity cannot yet be predicted from structure alone. 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. 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]], to over 2,500 residues in the animal [[fatty acid synthase]]. Only a small portion of their structure (around 2–4 amino acids) is directly involved in catalysis: the catalytic site. 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.
In some enzymes, no amino acids are directly involved in catalysis; instead, the enzyme contains sites to bind and orient catalytic [[cofactor (biochemistry)|cofactors]]. Enzyme structures may also contain [[allosteric site]]s where the binding of a small molecule causes a [[conformational change]] that increases or decreases activity.
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.
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== メカニズム ==
== Mechanism ==
{{Anchor|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.]]
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]].
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. This two-step process results in average error rates of less than 1 error in 100 million reactions in high-fidelity mammalian polymerases. [[aminoacyl tRNA synthetase]]s and [[ribosome]]s.
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.
[[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}})]]
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==== "鍵と錠"モデル ====
==== "Lock and key" model ====
1894年、酵素の特異性を説明するために、[[:en:Hermann Emil Fischer|Emil Fischer]]は、酵素と基質が互いにぴったりはまる特定の相補的な幾何学的形状を持っていると提唱した。これはしばしば「鍵と錠」モデルと呼ばれる。この初期のモデルでは、酵素の特異性は説明できるが、酵素が達成する遷移状態の安定化は説明できない。
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. This is often referred to as "the lock and key" model. This early model explains enzyme specificity, but fails to explain the stabilization of the transition state that enzymes achieve.
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==== 誘導適合モデル ====
==== Induced fit model ====
1958年、[[:en:Daniel E. Koshland, Jr.|Daniel Koshland]]は"鍵と錠"モデルの修正を提案した：酵素はどちらかというと柔軟な構造であるため、活性部位は基質が酵素と相互作用する際に、基質との相互作用によって絶えず再形成される。その結果、基質は単純に硬い活性部位に結合するのではなく、活性部位を構成するアミノ酸[[Side chain/ja|側鎖]]は、酵素が触媒機能を発揮できるような正確な位置に成形される。[[glycosidases/ja|グリコシダーゼ]]などの場合、基質[[molecule/ja|分子]]も活性部位に入るとわずかに形を変える。活性部位は基質が完全に結合するまで変化し続け、その時点で最終的な形状と電荷分布が決定される。
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. 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. The active site continues to change until the substrate is completely bound, at which point the final shape and charge distribution is determined.
Induced fit may enhance the fidelity of molecular recognition in the presence of competition and noise via the [[conformational proofreading]] mechanism.
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=== 触媒作用 ===
=== Catalysis ===
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{{See also/ja|Enzyme catalysis/ja|Transition state theory/ja}}
{{See also|Enzyme catalysis|Transition state theory}}
#* By orienting the substrates into a productive arrangement to reduce the reaction [[entropy]] change (the contribution of this mechanism to catalysis is relatively small)
Enzymes may use several of these mechanisms simultaneously. For example, [[protease]]s such as [[trypsin]] perform covalent catalysis using a [[catalytic triad]], stabilise charge build-up on the transition states using an [[oxyanion hole]], complete [[hydrolysis]] using an oriented water substrate.
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, consistent with [[catalytic resonance theory]].
[[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. 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.
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. 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.
[[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}})]]
Some enzymes do not need additional components to show full activity. Others require non-protein molecules called cofactors to be bound for activity. 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. 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]]).
An example of an enzyme that contains a cofactor is [[carbonic anhydrase]], which uses a zinc cofactor bound as part of its active site. These tightly bound ions or molecules are usually found in the active site and are involved in catalysis. For example, flavin and heme cofactors are often involved in [[redox]] reactions.
Enzymes that require a cofactor but do not have one bound are called ''apoenzymes'' 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.
Coenzymes are small organic molecules that can be loosely or tightly bound to an enzyme. Coenzymes transport chemical groups from one enzyme to another. 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 methyl group, carried by [[S-adenosylmethionine]]
Since coenzymes are chemically changed as a consequence of enzyme action, it is useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different enzymes. For example, about 1000 enzymes are known to use the coenzyme NADH.
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.
[[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.]]
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. For example, [[carbonic anhydrase]] catalyzes its reaction in either direction depending on the concentration of its reactants:
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.
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.
| 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).
| 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.
}}
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{{main/ja|Enzyme kinetics/ja}}
{{main|Enzyme kinetics}}
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酵素動力学とは、酵素がどのように基質と結合し、それを生成物に変えるかを調べることである。速度論的解析に用いられる速度データは、一般に[[:en:enzyme assay|酵素アッセイ]]から得られる。1913年に[[:en:Leonor Michaelis|レオノール・ミヒャエリス]]と[[:en:Maud Leonora Menten|モード・レオノーラ・メンテン]]は酵素速度論の定量的理論を提唱し、これは[[:en:Michaelis–Menten kinetics|ミヒャエリス・メンテン速度論]]と呼ばれる。ミカエリスとメンテンの主要な貢献は、酵素反応を2段階で考えることであった。まず、基質が酵素に可逆的に結合し、酵素-基質複合体が形成される。これをミカエリスとメンテンにちなんでミカエリス-メンテン複合体と呼ぶこともある。その後、酵素は反応の化学段階を触媒し、生成物を放出する。この研究は[[:en:George Edward Briggs|G. E.ブリッグス]]と[[J. B. S.ハルデン]]によってさらに発展し、今日でも広く使われている運動方程式を導いた。
Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products. 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]]. 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. E. Briggs]] and [[J. B. S. Haldane]], who derived kinetic equations that are still widely used today.
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.
''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.
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]]. The turnover of such enzymes can reach several million reactions per second. 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.
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ミカエリス・メンテン動力学は、自由な[[:en:diffusion|拡散]]と熱力学的に駆動されるランダムな衝突という仮定から導かれる[[:en:law of mass action|質量作用の法則]]に依存している。多くの生化学プロセスや細胞内プロセスは、[[macromolecular crowding/ja|高分子の混雑]]や制約された分子運動のために、これらの条件から大きく逸脱している。最近の複雑なモデルの拡張は、これらの効果を補正しようとするものである。
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. More recent, complex extensions of the model attempt to correct for these effects.
| 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.
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{{main/ja|Enzyme inhibitor/ja}}
{{main|Enzyme inhibitor}}
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酵素反応速度は、様々な種類の酵素阻害剤によって低下する。
Enzyme reaction rates can be decreased by various types of enzyme inhibitors.
A [[competitive inhibitor]] and substrate cannot bind to the enzyme at the same time. 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. 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.
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.
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. This type of inhibition is rare.
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.
An [[irreversible inhibitor]] permanently inactivates the enzyme, usually by forming a [[covalent bond]] to the protein. [[Penicillin]] and [[aspirin]] are common drugs that act in this manner.
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.
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阻害剤は酵素の機能を調節するので、しばしば薬物として用いられる。そのような薬物の多くは、上記の[[methotrexate/ja|メトトレキサート]]のような、酵素本来の基質に似た可逆的な競合阻害剤である。他のよく知られた例としては、高[[cholesterol/ja|コレステロール]]の治療に用いられる[[statin/ja|スタチン]]や、[[HIV/ja|HIV]]のような[[retroviral/ja|レトロウイルス]]感染の治療に用いられる[[protease inhibitors/ja|プロテアーゼ阻害剤]]がある。薬物として使用される不可逆的阻害剤の一般的な例は[[aspirin/ja|アスピリン]]であり、これは[[inflammation/ja|炎症]]のメッセンジャーである[[prostaglandin/ja|プロスタグランジン]]を生成する[[Cyclooxygenase/ja|COX-1]]と[[Cyclooxygenase/ja|COX-2]]の酵素を阻害する。他の酵素阻害剤は毒である。例えば、毒[[cyanide/ja|シアン化合物]]は不可逆的な酵素阻害剤であり、酵素[[cytochrome c oxidase/ja|シトクロムcオキシダーゼ]]の活性部位にある銅と鉄と結合し、[[cellular respiration/ja|細胞呼吸]]を阻害する。
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]], and [[protease inhibitors]] used to treat [[retroviral]] infections such as [[HIV]]. 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]]. 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]].
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== 酵素活性に影響を与える因子 ==
== Factors affecting enzyme activity ==
{{Anchor|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.
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. 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]]. 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]]. [[Virus]]es can also contain enzymes for infecting cells, such as the [[HIV integrase]] and [[reverse transcriptase]], or for viral release from cells, like the [[influenza]] virus [[neuraminidase]].
An important function of enzymes is in the [[digestive systems]] of animals. Enzymes such as [[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.
[[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. 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.
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 key steps, typically through enzymes whose activity involves the hydrolysis of 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.
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=== 活性の制御 ===
=== Control of activity ===
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酵素活性が細胞内で制御されるには、主に5つの方法がある。
There are five main ways that enzyme activity is controlled in the cell.
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. 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.
Examples of [[post-translational modification]] include [[phosphorylation]], [[myristoylation]] and [[glycosylation]]. For example, in the response to [[insulin]], the [[phosphorylation]] of multiple enzymes, including [[glycogen synthase]], helps control the synthesis or degradation of [[glycogen]] and allows the cell to respond to changes in [[blood sugar]]. 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]] or proenzyme.
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. 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. Enzyme levels can also be regulated by changing the rate of enzyme [[catabolism|degradation]]. The opposite of enzyme induction is [[enzyme repression]].
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]]. 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. In contrast to partitioning into membrane bound organelles, enzyme subcellular localisation may also be altered through polymerisation of enzymes into macromolecular cytoplasmic filaments.
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. This enzyme is involved in sensing [[blood sugar]] and regulating insulin production.
[[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|酵素の遺伝的欠陥は一般的に、非X染色体がX染色体よりも多いために[[autosomal inheritance/ja|染色体]]遺伝する傾向があり、また、無効な遺伝子からの酵素が通常の遺伝子から来る酵素に比べて十分であるため、それが担体に症状を防ぐことができるため、[[recessive inheritance/j|劣性]]遺伝する傾向がある。]]
[[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.]]
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]].
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. This can lead to [[intellectual disability]] if the disease is untreated.
Oral administration of enzymes can be used to treat some functional enzyme deficiencies, such as [[pancreatic insufficiency]] and [[lactose intolerance]].
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]].
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== 進化 ==
== Evolution ==
{{Anchor|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. 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.
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. 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.
* {{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}}
* {{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}}
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;語源と歴史
;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.
* {{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.
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{{Col-2-of-2}}
{{Col-2-of-2}}
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;酵素の構造とメカニズム
;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 }}
* {{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 }}
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;動態と阻害
;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 }}
* {{cite book | vauthors = Cornish-Bowden A | title = Fundamentals of Enzyme Kinetics | date = 2012 | publisher = Wiley-VCH | location = Weinheim | isbn = 978-3527330744 | edition = 4th }}
酵素動力学とは、酵素がどのように基質と結合し、それを生成物に変えるかを調べることである。速度論的解析に用いられる速度データは、一般に酵素アッセイから得られる。1913年にレオノール・ミヒャエリスとモード・レオノーラ・メンテンは酵素速度論の定量的理論を提唱し、これはミヒャエリス・メンテン速度論と呼ばれる。ミカエリスとメンテンの主要な貢献は、酵素反応を2段階で考えることであった。まず、基質が酵素に可逆的に結合し、酵素-基質複合体が形成される。これをミカエリスとメンテンにちなんでミカエリス-メンテン複合体と呼ぶこともある。その後、酵素は反応の化学段階を触媒し、生成物を放出する。この研究はG. E.ブリッグスとJ. B. S.ハルデンによってさらに発展し、今日でも広く使われている運動方程式を導いた。
Berg JM, Tymoczko JL, Stryer L (2002). Biochemistry (5th ed.). New York, NY: W. H. Freeman. ISBN0-7167-3051-0., A biochemistry textbook available free online through NCBI Bookshelf.
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