Difference between revisions of "Enzyme" - New World Encyclopedia

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[[Image:Triosephosphate isomerase.jpg|thumb|310px|Ribbon diagram of the enzyme [[triosephosphateisomerase|TIM]]. Each enzyme has a specific three-dimensional structure that determines its function.]]
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[[Category:Public]]
An '''enzyme''' is a [[protein]] that [[catalyst|catalyzes]], or speeds up, a [[chemical reaction]]. The word comes from the [[Greek language|Greek]] ένζυμο, ''énsymo'', which comes from ''én'' ("at" or "in") and ''simo'' ("[[leaven]]" or "[[yeast]]"). Certain [[RNA]]s also have catalytic activity, but to differentiate them from protein enzymes, they are referred to as RNA enzymes or [[ribozyme]]s.
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[[Image:Triosephosphate isomerase.jpg|thumb|310px|Ribbon diagram of the '''enzyme''' [[triosephosphateisomerase|TIM]]. Each enzyme has a specific three-dimensional structure that determines its function.]]
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An '''enzyme''' is a biological catalyst that regulates the rate of a chemical reaction in a living organism. Most enzymes are [[protein]]s, though certain [[nucleic acid]]s, called [[ribozyme]]s, are also capable of catalytic activity.  
  
Enzymes are essential to sustain [[life]] because most chemical reactions in [[cell (biology)|biological cell]]s would occur too slowly, or would lead to different products without enzymes. A malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a severe disease. For example, the most common type of [[phenylketonuria]] is caused by a single [[amino acid]] mutation in the enzyme [[phenylalanine hydroxylase]], which catalyzes the first step in the degradation of [[phenylalanine]]. The resulting build-up of phenylalanine and related products can lead to [[mental retardation]] if the disease is untreated.
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Enzymes are essential to sustain [[life]] because most chemical reactions in biological [[cell (biology)|cells]], such as the digestion of food, would occur too slowly or would lead to different products without the activity of enzymes. Most inherited human [[disease]]s result from a genetic [[mutation]], overproduction, or deficiency of a single critical enzyme. For example, lactose intolerance, the inability to digest significant amounts of lactose, which is the major sugar found in [[milk]], is caused by a shortage of the enzyme lactase.
  
Like all catalysts, enzymes work by providing an alternate pathway of lower [[activation energy]] of a reaction, thus allowing the reaction to proceed much faster. Enzymes may speed up reactions by a factor of many millions. An enzyme, like any catalyst, remains unaltered by the completed reaction and can therefore continue to function. Because enzymes do not affect the relative energy between the products and reagents, they do not affect [[Chemical equilibrium|equilibrium]] of a reaction. However, the advantage of enzymes compared to most other catalysts is their sterio-, regio- and chemoselectivity and specificity.
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For an enzyme to be functional, it must fold into a precise three-dimensional shape. How such a complex folding can take place remains a mystery. A small chain of 150 [[amino acid|amino acids]] making up an enzyme has an extraordinary number of possible folding configurations: if it tested 10<sup>12</sup> different configurations every second, it would take about 10<sup>26</sup> years to find the right one (Lewis 2005). Yet, a denatured enzyme can refold within fractions of a second and then precisely react in a chemical reaction. To some, it suggests that [[quantum mechanics|quantum effects]] are at work even at the large distances (by atomic standards) spanned by a protein molecule. At least, it demonstrates a stunning complexity and harmony in the universe.  
  
Enzyme activity can be affected by other [[molecules]]. [[inhibitor|Inhibitors]] are naturally occurring or synthetic molecules that decrease or abolish enzyme activity; activators are molecules that increase activity. Some irreversible inhibitors bind enzymes very tightly, effectively inactivating them. Many drugs and poisons act by inhibiting enzymes. [[Aspirin]] inhibits the [[Cyclooxygenase|COX-1]] and [[Cyclooxygenase|COX-2]] enzymes that produce the [[inflammation]] messenger [[prostaglandin]], thus suppressing pain and inflammation. The poison [[cyanide]] inhibits [[cytochrome c oxidase]], which effectively blocks [[cellular respiration]].
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While all enzymes have a biological role, some enzymes are also used commercially. For instance, many household cleaners use enzymes to speed up the breakdown of protein or starch stains on clothes.
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{{toc}}
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Like all catalysts, enzymes work to lower the activation energy of a reaction, or the initial [[energy]] input necessary for most chemical reactions to occur. Heat cannot be added to a living system, so enzymes provide an alternate pathway: they bond with a substrate (the substance involved in the chemical reaction) to form a “transition state,” an unstable intermediate complex that requires less energy for the reaction to proceed. Like any catalyst, the enzyme remains unaltered by the completed reaction and can therefore continue to interact with substrates. Enzymes may speed up reactions by a factor of many millions.
  
While all enzymes have a biological role, some enzymes are used commercially for other purposes. Many household cleaners use enzymes to speed up chemical reactions ( ''e.g.'', breaking down protein or starch stains in clothes).
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Enzymes can be affected by molecules that increase their activity (activators) or decrease their activity (inhibitors). Many drugs act by inhibiting enzymes. Aspirin works by inhibiting COX-1 and COX-2, the enzymes that produce prostaglandin, a hormonal messenger that signals inflammation. By inhibiting the activity of these enzymes, aspirin suppresses our experience of [[pain]] and inflammation.  
 
 
More than 5,000 enzymes are known. Typically the suffix ''-ase'' is added to the name of the [[substrate (biochemistry)|substrate]] (''e.g.'', [[lactase]] is the enzyme that catalyzes the cleavage of [[lactose]]) or the type of reaction (''e.g.,'' [[DNA polymerase]] catalyzes the formation of DNA polymers). However, this is not always the case, especially when enzymes modify multiple substrates. For this reason Enzyme Commission or [[EC number]]s are used to classify enzymes based on the reactions they catalyze. Even this is not a perfect solution, as enzymes from different species or even very similar enzymes in the same species may have identical EC numbers.
 
  
 
==The structure of enzymes==
 
==The structure of enzymes==
Enzyme structure is important because it determines the enzyme's particular function in the body. Enzymes (and other proteins) are composed of amino acid chains; the linear sequence of amino acids determines the characteristic folding of the chains into a three-dimensional structure. An enzyme might contain only one polypeptide chain, typically linking one hundred or more [[amino acid]]s, or it might consist of several polypeptide chains that act together as a unit.
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Enzyme structure is important because it determines the enzyme's particular function in the body. Enzymes (and other proteins) are composed of [[amino acid]] chains called polypeptide chains. The linear sequence of amino acids determines the characteristic folding of the chains into a three-dimensional structure. An enzyme might contain only one polypeptide chain, typically linking one hundred or more amino acids, or it might consist of several polypeptide chains that act together as a unit.
  
[[Image:Enzymeactivesite.png|thumb|right|300px|The active site of an enzyme.]]
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Most enzymes are larger than the substrates on which they act. Only a very small portion of the enzyme, approximately ten amino acids, comes into direct contact with the substrate(s). This region, where the binding of the substrate(s) and the reaction occur, is known as the active site of the enzyme.  
Most enzymes are larger than the substrates on which they act. Only a very small portion of the enzyme, approximately 10 amino acids, comes into direct contact with the substrate(s). This region, where the binding of the substrate(s) and the reaction occur, is known as the [[active site]] of the enzyme.  
 
  
 
===Specificity===
 
===Specificity===
Enzymes are usually specific as to the reactions they catalyze and the [[substrate (biochemistry)|substrate]]s that are involved in these reactions. An enzyme combines with its substrate(s) to form a short-lived enzyme-substrate complex. There are two models to explain how the binding of enzyme and substrate occurs: "lock and key" and induced fit.
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Enzymes are usually specific, or unique, to the reactions they catalyze and the substrates that are involved in these reactions. An enzyme combines with its substrate(s) to form a short-lived enzyme-substrate complex. There are two models to explain how the binding of enzyme and substrate occurs: the "lock and key" model and induced fit.
  
 
===="Lock and key" model====
 
===="Lock and key" model====
[[Image:Two substrates b.png|thumb|300px|The induced fit model of enzyme action.]]
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[[Image:Two substrates b.png|thumb|300px|The induced fit model of enzyme action]]
  
To account for the specificity of enzymes, [[Emil Fischer]] proposed that the enzyme had a particular shape into which the substrate(s) fit exactly. This model of exact fit, introduced in the 1890s, is often referred to as the "lock and key" model.  
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To account for the specificity of enzymes, Emil Fischer proposed that the enzyme had a particular shape into which the substrate(s) fit exactly. This model of exact fit, introduced in the 1890s, is often referred to as the "lock and key" model, because the enzyme binding to a substrate is analogous to the specific fit of a lock into a key.  
  
 
====Induced fit model====
 
====Induced fit model====
In 1958, [[Daniel Koshland]] suggested a modification to the "lock and key" model. Enzymes are rather flexible structures. The active site of an enzyme can be modified as the substrate interacts with the enzyme, creating an "induced fit" between enzyme and substrate. The amino acids side chains that make up the active site are molded into a precise shape, which enables the enzyme to perform its catalytic function. In some cases, the substrate molecule changes shape slightly as it enters the active site.  
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In 1958, Daniel Koshland suggested a modification to the "lock and key" model. Unlike keys, enzymes are rather flexible structures. The active site of an enzyme can be modified as the substrate interacts with the enzyme, creating an "induced fit" between enzyme and substrate. The amino acids side chains that make up the active site are molded into a precise shape, which enables the enzyme to perform its catalytic function. In some cases, the substrate molecule changes shape slightly as it enters the active site.  
  
 
===Enzyme cofactors===
 
===Enzyme cofactors===
Some enzymes do not need any additional components to exhibit full activity. However, others require non-protein molecules to be bound for activity. Cofactors can be either [[inorganic]] (''e.g.'', metal ions and [[Iron-sulfur cluster]]s) or [[organic molecules|organic compounds]], which are also known as [[coenzyme]]s.
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Some enzymes do not need any additional components to exhibit full activity. However, others require non-protein molecules to be bound to the complex for efficient activity. Cofactors can be either [[inorganic]] (e.g., metal ions and iron-sulfur clusters) or [[organic molecules|organic compounds]], which are also known as [[coenzyme]]s.
  
Enzymes that require a cofactor, but do not have one bound are called [[apoenzyme]]s. An apoenzyme together with its cofactor(s) constitutes a [[holoenzyme]] (''i.e,'' the active form). Most cofactors are not covalently bound to an enzyme, but are closely associated. However, some cofactors known as [[prosthetic groups]] are covalently bound (''e.g.,'' [[thiamine pyrophosphate]] in certain enzymes).
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Most cofactors are not covalently bound to an enzyme, but are closely associated. However, some cofactors known as prosthetic groups are tightly bound to the enzyme through covalent bonds.
  
Most cofactors are either regenerated or chemically unchanged at the end of the reactions. Many cofactors are [[vitamin]]-derivatives and serve as carriers to transfer [[electron]]s, [[atom]]s, or [[functional group]]s from an enzyme to a substrate. Common examples are [[Nicotinamide adenine dinucleotide|NAD]] and [[NADP]], which are involved in electron transfer and [[coenzyme A]], which is involved in the transfer of [[acetyl]] groups.
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Most cofactors are either regenerated or chemically unchanged at the end of the reactions. Many cofactors are [[vitamin]]-derivatives. They serve as carriers during the reaction to transfer [[electron]]s, [[atom]]s, or functional groups from an enzyme to a substrate. Common examples include [[Nicotinamide adenine dinucleotide|NAD]] and [[NADP]], which are involved in electron transfer, and [[coenzyme A]], which is involved in the transfer of acetyl groups.
  
 
==How enzymes catalyze reactions==
 
==How enzymes catalyze reactions==
[[Image:activation2.png|thumb|300px|The energy required at each stage of a catalytic reaction.]]
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[[Image:activation2.png|thumb|300px|The energy required at each stage of a catalytic reaction]]
  
As with all catalysts, all reactions catalyzed by enzymes must be "spontaneous" (containing a net negative [[Gibbs free energy]]). With the enzyme, they run in the same direction as they would without the enzyme, just more quickly. However, the uncatalyzed, "spontaneous" reaction might lead to different products than the catalyzed reaction. Furthermore, enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive" a thermodynamically unfavorable one. For example, the cleavage of the high-energy compound [[Adenosine triphosphate|ATP]] is often used to drive other, energetically unfavorable chemical reactions.
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A reaction catalyzed by enzymes must be ''spontaneous''; that is, having a natural tendency to occur without needing an external push. (Thermodynamically speaking, the reaction must contain a net negative Gibbs free energy.) In other words, the reaction would run in the same direction without the enzyme, but would occur at a significantly slower rate. For example, the breakdown of food particles such as [[carbohydrate]]s into smaller sugar components occurs spontaneously, but the addition of enzymes such as amylases in our saliva makes the reaction occur quickly.
 
 
Enzymes catalyze the forward and backward reactions equally. They do not alter the equilibrium itself, but only the speed at which it is reached. [[Carbonic anhydrase]] catalyzes its reaction in either direction depending on the conditions.
 
: <math>\mathrm{CO_2 + H_2O
 
{}^\mathrm{\quad Carbonic\ anhydrase}
 
\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!
 
\overrightarrow{\qquad\qquad\qquad\qquad}
 
H_2CO_3}</math> (in [[Biological tissue|tissue]]s - high CO<sub>2</sub> concentration)
 
: <math>\mathrm{H_2CO_3
 
{}^\mathrm{\quad Carbonic\ anhydrase}
 
\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!
 
\overrightarrow{\qquad\qquad\qquad\qquad}
 
CO_2 + H_2O}</math> (in [[lung]]s - low CO<sub>2</sub> concentration)
 
  
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Enzymes can pair two or more reactions, so that a spontaneous reaction can be used to drive an unfavorable one. For example, the cleavage of the high-energy compound [[Adenosine triphosphate|ATP]] is often used to power other, energetically unfavorable chemical reactions, such as the building of proteins.
  
 
==Regulation of enzyme activity==
 
==Regulation of enzyme activity==
{{mergeto|inhibitor}}
 
  
[[Image:comp_inhib.png|thumb|400px|A competitive inhibitor binds reversibly to the active site of the enzyme, preventing the binding of substrate.]]
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[[Image:comp_inhib.png|thumb|400px|A competitive inhibitor binds reversibly to the active site of the enzyme, preventing the binding of substrate]]
[[Image:comp_inhib3.png|thumb|400px|Non-competitive inhibitors do not bind to the active site.]]
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[[Image:comp_inhib3.png|thumb|400px|Non-competitive inhibitors do not bind to the active site]]
  
 
Compounds called inhibitors can decrease enzyme reaction rates through competitive or non-competitive inhibition.
 
Compounds called inhibitors can decrease enzyme reaction rates through competitive or non-competitive inhibition.
  
===Competitive inhibition===
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In '''competitive inhibition''', the inhibitor binds directly to the active site as shown, preventing the binding of substrate. The substrate and inhibitor thus "compete" for the active site of the enzyme.  
In competitive inhibition, the inhibitor binds to the substrate binding site as shown (''right'' part b), thus preventing substrate binding.  
 
  
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'''Non-competitive inhibitors''' do not bind to the active site; rather, they bind to other parts of the enzyme, which can be remote from the active site. The extent of inhibition depends entirely on the inhibitor concentration and will not be affected by the substrate concentration. For example, the poison [[cyanide]] combines with the [[copper]] prosthetic groups of the enzyme cytochrome c oxidase to inhibit cellular respiration. This type of inhibition is typically irreversible, meaning that the enzyme will no longer function after interacting with the inhibitor.
  
===Non-competitive inhibition===
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Some non-competitive inhibitors work by physically blocking the active site. Others bind to the enzyme in a way that alters the three-dimensional structure of the enzyme (its ''conformation''); the change in the enzyme's structure distorts the active site, disabling the enzyme from binding with substrate. In this second form of noncompetitive inhibition, called allosteric inhibition, the inhibitor binds to an allosteric site, changing the shape of the enzyme molecule in a way that prevents it from reacting with the substrate.
Non-competitive inhibitors never bind to the active site, but to other parts of the enzyme that can be far away from the substrate binding site, consequently, there is no competition between the substrate and inhibitor for the enzyme. The extent of inhibition depends entirely on the inhibitor concentration and will not be affected by the substrate concentration. For example, [[cyanide]] combines with the [[copper]] prosthetic groups of the enzyme [[cytochrome c oxidase]], thus inhibiting [[cellular respiration]]. This type of inhibition is typically irreversible, meaning that the enzyme will no longer function.
 
  
By changing the [[Chemical conformation|conformation]] (the three-dimensional structure) of the enzyme, the inhibitors either disable the ability of the enzyme to bind or turn over its substrate. The enzyme-inhibitor (EI) and enzyme-inhibitor-substrate (EIS) complex have no catalytic activity.
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=== Allosteric control ===
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Allosteric inhibitors are often used to regulate [[metabolism|metabolic]] pathways, in which several enzymes work together in a specific order. 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. The end product(s) of such a pathway are often allosteric inhibitors for one of the first enzymes of the pathway (usually the first irreversible step, called the ''committed step''), thus regulating the amount of end product made by the pathways. This regulatory process is called negative feedback, because the amount of the end product produced is regulated by its own concentration.  
  
=== Allosteric enzymes ===
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Allosteric molecules can also activate or increase the activity of enzymes by changing the shape of the enzyme's active site in order to facilitate interaction with a substrate. This allosteric control of enzymatic action helps to maintain a stable internal environment in living organisms, by stimulating the production of supplies when needed and preventing the excess manufacture of end products once the demand has been met.
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. The end product(s) of such a 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.
 
  
 
== Enzyme-naming conventions ==
 
== Enzyme-naming conventions ==
By common convention, an enzyme's name consists of a description of what it does, with the word ending in ''-ase''. Examples are [[alcohol dehydrogenase]] and [[DNA polymerase]]. [[Kinase]]s are enzymes that transfer [[phosphate]] groups. This results in different enzymes with the same function having the same basic name; they are therefore distinguished by other characteristics, such as their optimal [[pH]] ([[alkaline phosphatase]]) or their location (membrane [[ATPase]]). Furthermore, the reversibility of chemical reactions means that the normal physiological direction of an enzyme's function may not be that observed under laboratory conditions. This can result in the same enzyme being identified with two different names: one stemming from the formal laboratory identification as described above, the other representing its behavior in the cell. For instance the enzyme formally known as ''xylitol:NAD+ 2-oxidoreductase (D-xylulose-forming)'' is more commonly referred to in the cellular physiological sense as ''D-xylulose reductase'', reflecting the fact that the function of the enzyme in the cell is actually the reverse of what is often seen under ''in vitro'' conditions.
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Enzymes are known for their specificity; that is, they often interact with only one substrate to catalyze a particular reaction. Thus, enzymes have often been named by adding the suffix ''-ase'' to the name of the substrate (e.g., lactase is the enzyme that catalyzes the breakdown of lactose). Not all enzymes have been named in this manner, so a more formal method of nomenclature has been developed to classify enzymes.
  
The [http://www.iubmb.unibe.ch/ International Union of Biochemistry and Molecular Biology] has developed a [[nomenclature]] for enzymes, the [[EC number]]s; each enzyme is described by a sequence of four numbers, preceded by "EC". The first number broadly classifies the enzyme based on its mechanism:
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The [http://www.iubmb.unibe.ch/ International Union of Biochemistry and Molecular Biology] has developed a nomenclature for enzymes, called EC numbers. The EC number describes each enzyme using a sequence of four numbers, preceded by "EC." The first number broadly classifies the enzyme based on how it functions to catalyze a reaction.
  
The toplevel classification is
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Under this system, enzymes are broadly organized into six major categories, based on the types of reactions they catalyze:
* EC 1 ''[[Oxidoreductase]]s'': catalyze [[oxidation]]/reduction reactions
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* EC 2 ''[[Transferase]]s'': transfer a [[functional group]] (e.g. a methyl or phosphate group)
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* EC 1 ''Oxidoreductases'' catalyze [[oxidation]]/reduction reactions, which involve [[electron]] transfer.
* EC 3 ''[[Hydrolase]]s'': catalyze the [[hydrolysis]] of various bonds
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* EC 2 ''Transferases'' transfer a chemical group called a functional group (e.g., a methyl or phosphate group) from one substance to another.
* EC 4 ''[[Lyase]]s'': cleave various bonds by means other than hydrolysis and oxidation
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* EC 3 ''Hydrolases'' catalyze the cleavage of chemical bonds through the addition of a water molecule [[hydrolysis]].
* EC 5 ''[[Isomerase]]s'': catalyze [[isomer]]ization changes within a single molecule
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* EC 4 ''Lyases'' cleave various bonds by means other than hydrolysis and oxidation.
* EC 6 ''[[Ligase]]s'': join two molecules with [[covalent bond]]s
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* EC 5 ''Isomerases'' transfer a group within a single molecule to form an isomer.
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* EC 6 ''Ligases'' join two molecules with [[covalent bond]]s.
  
 
The complete nomenclature can be browsed at http://www.chem.qmul.ac.uk/iubmb/enzyme/
 
The complete nomenclature can be browsed at http://www.chem.qmul.ac.uk/iubmb/enzyme/
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=== Etymology and history ===
 
=== Etymology and history ===
 
[[Image:Eduardbuchner.jpg|thumb|125px|left|[[Eduard Buchner]]]]
 
[[Image:Eduardbuchner.jpg|thumb|125px|left|[[Eduard Buchner]]]]
The word [[wiktionary:enzyme|enzyme]] comes from [[Greek language|Greek]]: ''"in leaven"''.
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The word [[enzyme]] derives from the [[Greek]] ένζυμο, énsymo, which comes from ''én'' ("at" or "in") and ''simo'' ("leaven" or "yeast"). Although the leavening of bread and fermentation of wine had been practiced for centuries, these processes were not understood to be the result of enzyme activity until the late nineteenth century.  
As early as the late [[1700s]] and early [[1800s]], the digestion of [[meat]] by stomach secretions and the conversion of starch to sugars by plant extracts and saliva were observed.
 
  
Studying the [[fermentation]] of sugar to alcohol by yeast, [[Louis Pasteur]] came to the conclusion that this fermentation was catalyzed by "[[Vitalism|ferments]]" in the yeast, which were thought to function only in the presence of living organisms.
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Studying the [[fermentation]] of sugar to alcohol by yeast, [[Louis Pasteur]] came to the conclusion that this fermentation was catalyzed by ferments in the yeast, which were thought to function only in the presence of living organisms. However, in 1897, Hans and Eduard Buchner inadvertently used yeast extracts to ferment sugar, despite the absence of living yeast cells. They were interested in making extracts of yeast cells for medical purposes, and, as one possible way of preserving them, they added large amounts of sucrose to the extract. To their surprise, they found that the sugar was fermented, even though there were no living yeast cells in the mixture. The term "enzyme" was used to describe the substance(s) in yeast extract that brought about the fermentation of sucrose. It was not until 1926 that the first enzyme was obtained in pure form.
 
 
In [[1897]], [[Hans Buchner|Hans]] and [[Eduard Buchner]] inadvertently used yeast extracts to ferment sugar, despite the absence of living yeast cells. They were interested in making extracts of yeast cells for medical purposes, and, as one possible way of preserving them, they added large amounts of sucrose to the extract. To their surprise, they found that the sugar was fermented, even though there were no living yeast cells in the mixture. The term "enzyme" was used to describe the substance(s) in yeast extract that brought about the fermentation of sucrose.
 
It was not until 1926, however, that the first enzyme was obtained in pure form.
 
  
 
=== Enzyme kinetics ===
 
=== Enzyme kinetics ===
In 1913, [[Leonor Michaelis]] and [[Maud Menten]] proposed a quantitative theory of [[enzyme kinetics]], which is referred to as [[Michaelis-Menten kinetics]]. Their work was further developed by G. E. Briggs and [[J. B. S. Haldane]], who derived numerous kinetic equations that are still widely used today.
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In 1913 Leonor Michaelis and Maud Menten proposed a quantitative theory of enzyme kinetics, which is referred to as Michaelis-Menten kinetics. Their work was further developed by G. E. Briggs and [[J. B. S. Haldane]], who derived numerous kinetic equations that are still widely used today.
  
Enzymes can perform up to several million catalytic reactions per second; to determine the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is achieved. This is the maximum velocity (''V''<sub>max</sub>) of the enzyme. In this state, all enzyme active sites are saturated with substrate. However, ''V''<sub>max</sub> is only one kinetic parameter that biochemists are interested in. The amount of substrate needed to achieve a given rate of reaction is also of interest. This can be expressed by the [[Michaelis-Menten constant]] (''K''<sub>m</sub>), which is the substrate concentration required for an enzyme to reach one half its maximum velocity. Each enzyme has a characteristic ''K''<sub>m</sub> for a given substrate.
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Enzymes can perform up to several million catalytic reactions per second. To determine the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is achieved. This rate is the maximum velocity (''V''<sub>max</sub>) of the enzyme. In this state, all enzyme active sites are saturated with substrate; that is, they are all engaged in converting substrate to product.  
  
The efficiency of an enzyme can be expressed in terms of ''k''<sub>cat</sub>/''K''<sub>m</sub>. The quantity ''k''<sub>cat</sub>, also called the [[turnover number]], incorporates the [[rate constants]] for all steps in the reaction, and is the quotient of ''V''<sub>max</sub> and the total enzyme concentration. ''k''<sub>cat</sub>/''K''<sub>m</sub> is a useful quantity for comparing different enzymes against each other, or the same enzyme with different substrates, because it takes both affinity and catalytic ability into consideration. The theoretical maximum for ''k''<sub>cat</sub>/''K''<sub>m</sub>, called the diffusion limit, 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 that reach this ''k''<sub>cat</sub>/''K''<sub>m</sub> value are called ''catalytically perfect'' or ''kinetically perfect''. Example of such enzymes are [[triosephosphateisomerase|triose-phosphate isomerase]], [[carbonic anhydrase]], [[acetylcholinesterase]], [[catalase]], fumarase, ß-lactamase, and [[superoxide dismutase]].
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However, ''V''<sub>max</sub> is only one kinetic parameter that interests biochemists. They also want to be able to calculate the amount of substrate needed to achieve a given rate of reaction. This amount can be expressed by the Michaelis-Menten constant (''K''<sub>m</sub>), which is the substrate concentration required for an enzyme to reach one half its maximum velocity. Each enzyme has a characteristic ''K''<sub>m</sub> for a given substrate.
  
Some enzymes operate with kinetics which are faster than diffusion rates, which would seem to be impossible. Several mechanisms have been invoked to explain this phenomenon. Some proteins are believed to accelerate catalysis by drawing their substrate in and preorienting them by using dipolar electric fields. Some invoke a quantum-mechanical [[quantum tunneling|tunneling]] explanation whereby a proton or an electron can tunnel through activation barriers, although for protons tunneling remains somewhat controversial. <ref>Mireia Garcia-Viloca,1 Jiali Gao,1 Martin Karplus,2* Donald G. Truhlar Science 9 January 2004:
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The efficiency of an enzyme can be expressed in terms of ''k''<sub>cat</sub>/''K''<sub>m</sub>. The quantity ''k''<sub>cat</sub>, also called the turnover number, incorporates the rate constants for all steps in the reaction, and is the quotient of ''V''<sub>max</sub> and the total enzyme concentration. ''k''<sub>cat</sub>/''K''<sub>m</sub> is a useful quantity for comparing the relative efficiencies of different enzymes, or the same enzyme interacting with different substrates, because it takes both affinity and catalytic ability into consideration. The theoretical maximum for ''k''<sub>cat</sub>/''K''<sub>m</sub>, called the diffusion limit, 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 that reach this ''k''<sub>cat</sub>/''K''<sub>m</sub> value are called ''catalytically perfect'' or ''kinetically perfect''. Example of such enzymes include triose-phosphate isomerase (or TIM), carbonic anhydrase, acetylcholinesterase, catalase, fumarase, ß-lactamase, and superoxide dismutase.
Vol. 303. no. 5655, pp. 186 - 195</ref><ref>
 
Olsson MH, Siegbahn PE, Warshel A. J Am Chem Soc. 2004 Mar 10;126(9):2820-8.</ref>
 
  
=== Industrial Applications ===
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=== Industrial applications ===
{| border=1 cellspacing="0" cellpadding=2 style="border:1px solid #aaaaaa;"
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Below are some common applications of enzymes, which have played an increased role in industrial processes since the scientific understanding of their catalytic function in the late nineteenth century:
|-
 
| bgcolor="#C0C0C0" | <p align="center"><font color="#FFFFFF">'''Application'''</font>
 
| bgcolor="#C0C0C0" | <p align="center"><font color="#FFFFFF">'''Enzymes used'''</font>
 
| bgcolor="#C0C0C0" | <p align="center"><font color="#FFFFFF">'''Uses'''</font>
 
| bgcolor="#C0C0C0" | <p align="center"><font color="#FFFFFF">'''Notes and examples'''</font>
 
|-
 
|rowspan="2" valign="top" | '''[[Detergent|Biological detergent]]'''
 
| Primarily [[protease]]s, produced in an extracellular form from [[bacteria]]
 
| Used for presoak conditions and direct liquid applications helping with removal of protein stains from clothes.
 
|rowspan="2" | [[Image:Washingpowder.jpg|180px|center| ]]
 
|-
 
| Amylase enzymes
 
| Detergents for machine dish washing to remove resistant starch residues.
 
|-
 
|rowspan="2" | '''[[Baking|Baking industry]]'''
 
| [[Fungus|Fungal]] alpha-amylase enzymes: normally inactivates about 50 degrees Celsius, destroyed during baking process
 
| Catalyze breakdown of starch in the [[flour]] to sugar. Yeast action on sugar produces carbon dioxide. Used in production of white bread, buns, and rolls
 
|[[Image:Amylose.gif|thumb|center|300px|alpha-amylase catalyzes the release of sugar monomers from starch]]
 
|-
 
| Protease enzymes
 
| Biscuit manufacturers use them to lower the protein level of flour.
 
|rowspan="2" |
 
|-
 
| '''[[Baby food]]s'''
 
| [[Trypsin]]
 
| To predigest baby foods
 
|-
 
|rowspan="6" | '''[[Brewing|Brewing industry]]'''
 
| Enzymes from barley are released during the mashing stage of beer production.
 
| They degrade starch and proteins to produce simple sugar, amino acids and peptides that are used by yeast to enhance fermentation.
 
|rowspan="3" |[[Image:Sjb whiskey malt.jpg|thumb|center|180px|Germinating barley used for malt.]]
 
|-
 
| Industrially produced barley enzymes.
 
| Widely used in the brewing process to substitute for the natural enzymes found in barley.
 
|-
 
| Amylase, glucanases, proteases
 
| Split polysaccharides and proteins in the [[malt]]
 
|-
 
| Betaglucosidase
 
| Improve the filtration characteristics.
 
|rowspan="4" |
 
|-
 
| Amyloglucosidase
 
| Low-calorie [[beer]]
 
|-
 
| Proteases
 
| Remove cloudiness during storage of beers.
 
|-
 
| '''[[Juice|Fruit juices]]'''
 
| Cellulases, pectinases
 
| Clarify fruit juices
 
|-
 
|rowspan="4" | '''[[Dairy|Dairy industry]]'''
 
| Rennin, derived from the stomachs of young [[ruminant|ruminant animals]] (calves, lambs)
 
| Manufacture of cheese, used to split protein
 
|'''Note:''' As animals age rennin production decreases and is replaced by another protease, pepsin, which is not suitable for cheese production. In recent years the increase in cheese consumption, as well as increased beef production, has resulted in a shortage of rennin and escalating prices.
 
|-
 
| Microbially produced enzyme
 
| Now finding increasing use in the dairy industry
 
|rowspan="3" | [[Image:Roquefort cheese.jpg|thumb|center|180px|Roquefort cheese]]
 
|-
 
| [[Lipase]]s
 
| Is implemented during the production of [[Roquefort cheese]] to enhance the ripening of the [[Danish Blue cheese|blue-mould cheese]].
 
|-
 
| Lactases
 
| Break down lactose to glucose and galactose
 
|-
 
|rowspan="2"| '''[[Starch|Starch industry]]'''
 
| Amylases, amyloglucosideases and glucoamylases
 
| Converts starch into glucose and various [[Inverted sugar syrup|syrups]]
 
|rowspan= "2"|<div class="thumb center">
 
<div style="width:308px;">
 
{| style="background:none;" cellspacing="0"
 
|[[Image:Glucose.png|150px| ]]
 
|[[image: Alpha-D-Fructose-structure-corrected.png|150px| ]]
 
|-
 
|<div class="thumbcaption">'''Glucose'''</div>
 
|<div class="thumbcaption">'''Fructose'''</div>
 
|-
 
|}
 
</div></div>
 
|-
 
| Glucose isomerase
 
| Converts [[glucose]] into fructose (high fructose syrups derived from starchy materials have enhanced sweetening properties and lower [[calorie|calorific values]])
 
|-
 
| '''[[Rubber|Rubber industry]]'''
 
| [[Catalase]]
 
| To generate [[oxygen]] from [[peroxide]] to convert [[latex]] to foam rubber
 
|
 
|-
 
| '''[[Paper|Paper industry]]'''
 
| [[Amylase]]s
 
| Degrade starch to lower [[viscosity]] product needed for sizing and coating paper
 
|[[Image:InternationalPaper6413.JPG|180px|center| ]]
 
|-
 
| '''[[Photography|Photographic industry]]'''
 
| Protease (ficin)
 
| Dissolve [[gelatin]] off the scrap [[Photographic film|film]] allowing recovery of [[silver]] present
 
|
 
|-
 
|}
 
  
 +
[[Image:Washingpowder.jpg|180px|left| ]]
 +
''Proteases'', which function in the breakdown of the bonds between the [[amino acid]]s that constitute [[protein]] molecules, are used in biological detergents to help with the removal of protein stains. Rennin, a type of protease that is derived from the stomachs of young ruminant animals (calves, lambs), is used to split protein during the manufacture of [[cheese]]. Another type of protease called trypsin is used to pre-digest baby foods.
 +
*''Amylase'', a digestive enzyme used in the breakdown of [[carbohydrate]]s, helps to remove resistant starch residues in dishwashing detergents. Fungal-alpha amylase enzymes catalyze the breakdown of starch in flour into its component sugars; they are used in the production of white bread, buns, and rolls.
 +
[[Image:Sjb whiskey malt.jpg|thumb|right|180px|Germinating barley used for malt]]
 +
*The brewing industry utilizes a variety of enzymes released from the malt (often the grain [[barley]]) during the mashing stage of beer production, in which the barley and water are combined and heated. These enzymes, which include amylases, glucanases, and proteases, degrade starches and proteins in the malt to produce simple sugar, amino acids and peptides that enhance fermentation.
  
 
== References ==
 
== References ==
* Koshland D. The Enzymes, v. I, ch. 7, Acad. Press, New York, 1959
+
* Briggs, G. E. & J. B. S. Haldane. 1925. A note on the kinetics of enzyme action, ''Biochem. J.'' 19:339-339.
* Perutz M. ''Proc. Roy. Soc.'', B (1967) 167, 448,
+
* Cha, Y., C. J. Murray, & J. P. Klinman. 1989. ''Science'' 243: 1325-1330.
* Cha, Y., Murray, C. J. & Klinman, J. P. ''Science'' (1989) 243, 1325-1330 .
+
* Koshland, D. 1959. ''The Enzymes''. New York: Academic Press.
* [[Leonor Michaelis]] and [[Maud Menten]], Die Kinetik der Invertinwirkung, ''Biochem. Z.'' (1913) 49, 333-369.
+
* Lewis, R. L. 2005. ''Do Proteins Teleport in an RNA World''. New York: International Conference on the Unity of the Sciences.
* G. E. Briggs and [[J. B. S. Haldane]], A note on the kinetics of enzyme action, ''Biochem. J.'', (1925) 19, 339-339.
+
* Michaelis, L. and M. Menten. 1913. Die Kinetik der Invertinwirkung, ''Biochem. Z.'' 49:333-369.
* M.V. Volkenshtein, R.R. [[Revaz Dogonadze|Dogonadze]], A.K. Madumarov, Z.D. Urushadze, Yu.I. Kharkats. Theory of Enzyme Catalysis.- ''Molekuliarnaya Biologia'', (1972), 431-439 (In Russian, English summary)
+
* Perutz, M. 1967. ''Proc. Roy. Soc''. 167: 448.
 
+
* Volkenshtein, M.V., R.R. Dogonadze, A.K. Madumarov, Z.D. Urushadze, & Yu.I. Kharkats. 1972. Theory of Enzyme Catalysis, ''Molekuliarnaya Biologia''. 431-439 (In Russian, English summary).
== External links ==
 
  
* [http://us.expasy.org/enzyme/ ExPASy enzyme database], links to [[Swiss-Prot]] sequence data, entries in other databases and to related literature searches
 
* [http://www.biochem.ucl.ac.uk/bsm/enzymes/ PDBsum] links to the known 3-D structure data of enzymes in the [[Protein Data Bank]]
 
* [http://www-mitchell.ch.cam.ac.uk/macie MACiE], database of enzyme reaction mechanisms
 
* [http://www.brenda.uni-koeln.de BRENDA], comprehensive compilation of information and literature references about all known enzymes; requires payment by commercial users
 
* [http://bioinformatics.weizmann.ac.il/cards/ Weizmann Institute's Genecards Database], extensive database of protein properties and their associated genes.
 
* [http://drnelson.utmem.edu/CytochromeP450.html Cytochrome P450 enzymes] site lists over 4000 versions of enzymes from this cytochrome in plants and animals
 
  
 
{{credit|52845583}}
 
{{credit|52845583}}
 
[[Category:Life sciences]]
 
[[Category:Life sciences]]
 +
[[Category:Biochemistry]]

Revision as of 14:59, 20 June 2013


Ribbon diagram of the enzyme TIM. Each enzyme has a specific three-dimensional structure that determines its function.

An enzyme is a biological catalyst that regulates the rate of a chemical reaction in a living organism. Most enzymes are proteins, though certain nucleic acids, called ribozymes, are also capable of catalytic activity.

Enzymes are essential to sustain life because most chemical reactions in biological cells, such as the digestion of food, would occur too slowly or would lead to different products without the activity of enzymes. Most inherited human diseases result from a genetic mutation, overproduction, or deficiency of a single critical enzyme. For example, lactose intolerance, the inability to digest significant amounts of lactose, which is the major sugar found in milk, is caused by a shortage of the enzyme lactase.

For an enzyme to be functional, it must fold into a precise three-dimensional shape. How such a complex folding can take place remains a mystery. A small chain of 150 amino acids making up an enzyme has an extraordinary number of possible folding configurations: if it tested 1012 different configurations every second, it would take about 1026 years to find the right one (Lewis 2005). Yet, a denatured enzyme can refold within fractions of a second and then precisely react in a chemical reaction. To some, it suggests that quantum effects are at work even at the large distances (by atomic standards) spanned by a protein molecule. At least, it demonstrates a stunning complexity and harmony in the universe.

While all enzymes have a biological role, some enzymes are also used commercially. For instance, many household cleaners use enzymes to speed up the breakdown of protein or starch stains on clothes.

Like all catalysts, enzymes work to lower the activation energy of a reaction, or the initial energy input necessary for most chemical reactions to occur. Heat cannot be added to a living system, so enzymes provide an alternate pathway: they bond with a substrate (the substance involved in the chemical reaction) to form a “transition state,” an unstable intermediate complex that requires less energy for the reaction to proceed. Like any catalyst, the enzyme remains unaltered by the completed reaction and can therefore continue to interact with substrates. Enzymes may speed up reactions by a factor of many millions.

Enzymes can be affected by molecules that increase their activity (activators) or decrease their activity (inhibitors). Many drugs act by inhibiting enzymes. Aspirin works by inhibiting COX-1 and COX-2, the enzymes that produce prostaglandin, a hormonal messenger that signals inflammation. By inhibiting the activity of these enzymes, aspirin suppresses our experience of pain and inflammation.

The structure of enzymes

Enzyme structure is important because it determines the enzyme's particular function in the body. Enzymes (and other proteins) are composed of amino acid chains called polypeptide chains. The linear sequence of amino acids determines the characteristic folding of the chains into a three-dimensional structure. An enzyme might contain only one polypeptide chain, typically linking one hundred or more amino acids, or it might consist of several polypeptide chains that act together as a unit.

Most enzymes are larger than the substrates on which they act. Only a very small portion of the enzyme, approximately ten amino acids, comes into direct contact with the substrate(s). This region, where the binding of the substrate(s) and the reaction occur, is known as the active site of the enzyme.

Specificity

Enzymes are usually specific, or unique, to the reactions they catalyze and the substrates that are involved in these reactions. An enzyme combines with its substrate(s) to form a short-lived enzyme-substrate complex. There are two models to explain how the binding of enzyme and substrate occurs: the "lock and key" model and induced fit.

"Lock and key" model

The induced fit model of enzyme action

To account for the specificity of enzymes, Emil Fischer proposed that the enzyme had a particular shape into which the substrate(s) fit exactly. This model of exact fit, introduced in the 1890s, is often referred to as the "lock and key" model, because the enzyme binding to a substrate is analogous to the specific fit of a lock into a key.

Induced fit model

In 1958, Daniel Koshland suggested a modification to the "lock and key" model. Unlike keys, enzymes are rather flexible structures. The active site of an enzyme can be modified as the substrate interacts with the enzyme, creating an "induced fit" between enzyme and substrate. The amino acids side chains that make up the active site are molded into a precise shape, which enables the enzyme to perform its catalytic function. In some cases, the substrate molecule changes shape slightly as it enters the active site.

Enzyme cofactors

Some enzymes do not need any additional components to exhibit full activity. However, others require non-protein molecules to be bound to the complex for efficient activity. Cofactors can be either inorganic (e.g., metal ions and iron-sulfur clusters) or organic compounds, which are also known as coenzymes.

Most cofactors are not covalently bound to an enzyme, but are closely associated. However, some cofactors known as prosthetic groups are tightly bound to the enzyme through covalent bonds.

Most cofactors are either regenerated or chemically unchanged at the end of the reactions. Many cofactors are vitamin-derivatives. They serve as carriers during the reaction to transfer electrons, atoms, or functional groups from an enzyme to a substrate. Common examples include NAD and NADP, which are involved in electron transfer, and coenzyme A, which is involved in the transfer of acetyl groups.

How enzymes catalyze reactions

The energy required at each stage of a catalytic reaction

A reaction catalyzed by enzymes must be spontaneous; that is, having a natural tendency to occur without needing an external push. (Thermodynamically speaking, the reaction must contain a net negative Gibbs free energy.) In other words, the reaction would run in the same direction without the enzyme, but would occur at a significantly slower rate. For example, the breakdown of food particles such as carbohydrates into smaller sugar components occurs spontaneously, but the addition of enzymes such as amylases in our saliva makes the reaction occur quickly.

Enzymes can pair two or more reactions, so that a spontaneous reaction can be used to drive an unfavorable one. For example, the cleavage of the high-energy compound ATP is often used to power other, energetically unfavorable chemical reactions, such as the building of proteins.

Regulation of enzyme activity

A competitive inhibitor binds reversibly to the active site of the enzyme, preventing the binding of substrate
Non-competitive inhibitors do not bind to the active site

Compounds called inhibitors can decrease enzyme reaction rates through competitive or non-competitive inhibition.

In competitive inhibition, the inhibitor binds directly to the active site as shown, preventing the binding of substrate. The substrate and inhibitor thus "compete" for the active site of the enzyme.

Non-competitive inhibitors do not bind to the active site; rather, they bind to other parts of the enzyme, which can be remote from the active site. The extent of inhibition depends entirely on the inhibitor concentration and will not be affected by the substrate concentration. For example, the poison cyanide combines with the copper prosthetic groups of the enzyme cytochrome c oxidase to inhibit cellular respiration. This type of inhibition is typically irreversible, meaning that the enzyme will no longer function after interacting with the inhibitor.

Some non-competitive inhibitors work by physically blocking the active site. Others bind to the enzyme in a way that alters the three-dimensional structure of the enzyme (its conformation); the change in the enzyme's structure distorts the active site, disabling the enzyme from binding with substrate. In this second form of noncompetitive inhibition, called allosteric inhibition, the inhibitor binds to an allosteric site, changing the shape of the enzyme molecule in a way that prevents it from reacting with the substrate.

Allosteric control

Allosteric inhibitors are often used to regulate metabolic pathways, in which several enzymes work together in a specific order. 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. The end product(s) of such a pathway are often allosteric inhibitors for one of the first enzymes of the pathway (usually the first irreversible step, called the committed step), thus regulating the amount of end product made by the pathways. This regulatory process is called negative feedback, because the amount of the end product produced is regulated by its own concentration.

Allosteric molecules can also activate or increase the activity of enzymes by changing the shape of the enzyme's active site in order to facilitate interaction with a substrate. This allosteric control of enzymatic action helps to maintain a stable internal environment in living organisms, by stimulating the production of supplies when needed and preventing the excess manufacture of end products once the demand has been met.

Enzyme-naming conventions

Enzymes are known for their specificity; that is, they often interact with only one substrate to catalyze a particular reaction. Thus, enzymes have often been named by adding the suffix -ase to the name of the substrate (e.g., lactase is the enzyme that catalyzes the breakdown of lactose). Not all enzymes have been named in this manner, so a more formal method of nomenclature has been developed to classify enzymes.

The International Union of Biochemistry and Molecular Biology has developed a nomenclature for enzymes, called EC numbers. The EC number describes each enzyme using a sequence of four numbers, preceded by "EC." The first number broadly classifies the enzyme based on how it functions to catalyze a reaction.

Under this system, enzymes are broadly organized into six major categories, based on the types of reactions they catalyze:

  • EC 1 Oxidoreductases catalyze oxidation/reduction reactions, which involve electron transfer.
  • EC 2 Transferases transfer a chemical group called a functional group (e.g., a methyl or phosphate group) from one substance to another.
  • EC 3 Hydrolases catalyze the cleavage of chemical bonds through the addition of a water molecule hydrolysis.
  • EC 4 Lyases cleave various bonds by means other than hydrolysis and oxidation.
  • EC 5 Isomerases transfer a group within a single molecule to form an isomer.
  • EC 6 Ligases join two molecules with covalent bonds.

The complete nomenclature can be browsed at http://www.chem.qmul.ac.uk/iubmb/enzyme/

Related Topics

Etymology and history

Eduard Buchner

The word enzyme derives from the Greek ένζυμο, énsymo, which comes from én ("at" or "in") and simo ("leaven" or "yeast"). Although the leavening of bread and fermentation of wine had been practiced for centuries, these processes were not understood to be the result of enzyme activity until the late nineteenth century.

Studying the fermentation of sugar to alcohol by yeast, Louis Pasteur came to the conclusion that this fermentation was catalyzed by ferments in the yeast, which were thought to function only in the presence of living organisms. However, in 1897, Hans and Eduard Buchner inadvertently used yeast extracts to ferment sugar, despite the absence of living yeast cells. They were interested in making extracts of yeast cells for medical purposes, and, as one possible way of preserving them, they added large amounts of sucrose to the extract. To their surprise, they found that the sugar was fermented, even though there were no living yeast cells in the mixture. The term "enzyme" was used to describe the substance(s) in yeast extract that brought about the fermentation of sucrose. It was not until 1926 that the first enzyme was obtained in pure form.

Enzyme kinetics

In 1913 Leonor Michaelis and Maud Menten proposed a quantitative theory of enzyme kinetics, which is referred to as Michaelis-Menten kinetics. Their work was further developed by G. E. Briggs and J. B. S. Haldane, who derived numerous kinetic equations that are still widely used today.

Enzymes can perform up to several million catalytic reactions per second. To determine the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is achieved. This rate is the maximum velocity (Vmax) of the enzyme. In this state, all enzyme active sites are saturated with substrate; that is, they are all engaged in converting substrate to product.

However, Vmax is only one kinetic parameter that interests biochemists. They also want to be able to calculate the amount of substrate needed to achieve a given rate of reaction. This amount can be expressed by the Michaelis-Menten constant (Km), which is the substrate concentration required for an enzyme to reach one half its maximum velocity. Each enzyme has a characteristic Km for a given substrate.

The efficiency of an enzyme can be expressed in terms of kcat/Km. The quantity kcat, also called the turnover number, incorporates the rate constants for all steps in the reaction, and is the quotient of Vmax and the total enzyme concentration. kcat/Km is a useful quantity for comparing the relative efficiencies of different enzymes, or the same enzyme interacting with different substrates, because it takes both affinity and catalytic ability into consideration. The theoretical maximum for kcat/Km, called the diffusion limit, is about 108 to 109 (M-1 s-1). 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 that reach this kcat/Km value are called catalytically perfect or kinetically perfect. Example of such enzymes include triose-phosphate isomerase (or TIM), carbonic anhydrase, acetylcholinesterase, catalase, fumarase, ß-lactamase, and superoxide dismutase.

Industrial applications

Below are some common applications of enzymes, which have played an increased role in industrial processes since the scientific understanding of their catalytic function in the late nineteenth century:

Proteases, which function in the breakdown of the bonds between the amino acids that constitute protein molecules, are used in biological detergents to help with the removal of protein stains. Rennin, a type of protease that is derived from the stomachs of young ruminant animals (calves, lambs), is used to split protein during the manufacture of cheese. Another type of protease called trypsin is used to pre-digest baby foods.

  • Amylase, a digestive enzyme used in the breakdown of carbohydrates, helps to remove resistant starch residues in dishwashing detergents. Fungal-alpha amylase enzymes catalyze the breakdown of starch in flour into its component sugars; they are used in the production of white bread, buns, and rolls.
Germinating barley used for malt
  • The brewing industry utilizes a variety of enzymes released from the malt (often the grain barley) during the mashing stage of beer production, in which the barley and water are combined and heated. These enzymes, which include amylases, glucanases, and proteases, degrade starches and proteins in the malt to produce simple sugar, amino acids and peptides that enhance fermentation.

References
ISBN links support NWE through referral fees

  • Briggs, G. E. & J. B. S. Haldane. 1925. A note on the kinetics of enzyme action, Biochem. J. 19:339-339.
  • Cha, Y., C. J. Murray, & J. P. Klinman. 1989. Science 243: 1325-1330.
  • Koshland, D. 1959. The Enzymes. New York: Academic Press.
  • Lewis, R. L. 2005. Do Proteins Teleport in an RNA World. New York: International Conference on the Unity of the Sciences.
  • Michaelis, L. and M. Menten. 1913. Die Kinetik der Invertinwirkung, Biochem. Z. 49:333-369.
  • Perutz, M. 1967. Proc. Roy. Soc. 167: 448.
  • Volkenshtein, M.V., R.R. Dogonadze, A.K. Madumarov, Z.D. Urushadze, & Yu.I. Kharkats. 1972. Theory of Enzyme Catalysis, Molekuliarnaya Biologia. 431-439 (In Russian, English summary).


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