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Human glyoxalase I. Two zinc ions that are needed for the enzyme to catalyze its reaction are shown as purple spheres, and an enzyme inhibitor called S-hexylglutathione is shown as a space-filling model, filling the two active sites.





Etymology and history

As early as the late 17th and early 18th centuries, the digestion of meat by stomach secretions[7] and the conversion of starch to sugars by plant extracts and saliva were known. However, the mechanism by which this occurred had not been identified.[8]

In 1833, French chemist Anselme Payen discovered the first enzyme, diastase.[9] A few decades later, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur came to the conclusion that this fermentation was catalyzed by a vital force contained within the yeast cells called "ferments", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells."[10]


In 1897, Eduard Buchner submitted his first paper on the ability of yeast extracts that lacked any living yeast cells to ferment sugar. In a series of experiments at the University of Berlin, he found that the sugar was fermented even when there were no living yeast cells in the mixture.[12] He named the enzyme that brought about the fermentation of sucrose "zymase".[13] In 1907, he received the Nobel Prize in Chemistry "for his biochemical research and his discovery of cell-free fermentation". Following Buchner's example, enzymes are usually named according to the reaction they carry out. Typically, to generate the name of an enzyme, the suffix -ase is added to the name of its substrate (e.g., lactase is the enzyme that cleaves lactose) or the type of reaction (e.g., DNA polymerase forms DNA polymers).[14]

Having shown that enzymes could function outside a living cell, the next step was to determine their biochemical nature. Many early workers noted that enzymatic activity was associated with proteins, but several scientists (such as Nobel laureate Richard Willstätter) argued that proteins were merely carriers for the true enzymes and that proteins per se were incapable of catalysis.[15] However, in 1926, James B. Sumner showed that the enzyme urease was a pure protein and crystallized it; Sumner did likewise for the enzyme catalase in 1937. The conclusion that pure proteins can be enzymes was definitively proved by Northrop and Stanley, who worked on the digestive enzymes pepsin (1930), trypsin and chymotrypsin. These three scientists were awarded the 1946 Nobel Prize in Chemistry.[16]


Structures and mechanisms

Ribbon diagram showing human carbonic anhydrase II. The grey sphere is the zinc cofactor in the active site. Diagram drawn from PDB 1MOO.

Enzymes are in general globular proteins and range from just 62 amino acid residues in size, for the monomer of 4-oxalocrotonate tautomerase,[18] to over 2,500 residues in the animal fatty acid synthase.[19] A small number of RNA-based biological catalysts exist, with the most common being the ribosome; these are referred to as either RNA-enzymes or ribozymes. The activities of enzymes are determined by their three-dimensional structure.[20] However, although structure does determine function, predicting a novel enzyme's activity just from its structure is a very difficult problem that has not yet been solved.[21]

Most enzymes are much larger than the substrates they act on, and only a small portion of the enzyme (around 2–4 amino acids) is directly involved in catalysis.[22] The region that contains these catalytic residues, binds the substrate, and then carries out the reaction is known as the active site. Enzymes can also contain sites that bind cofactors, which are needed for catalysis. Some enzymes also have binding sites for small molecules, which are often direct or indirect products or substrates of the reaction catalyzed. This binding can serve to increase or decrease the enzyme's activity, providing a means for feedback regulation.

Like all proteins, enzymes are long, linear chains of amino acids that fold to produce a three-dimensional product. Each unique amino acid sequence produces a specific structure, which has unique properties. Individual protein chains may sometimes group together to form a protein complex. Most enzymes can be denatured—that is, unfolded and inactivated—by heating or chemical denaturants, which disrupt the three-dimensional structure of the protein. Depending on the enzyme, denaturation may be reversible or irreversible.

Structures of enzymes with substrates or substrate analogs during a reaction may be obtained using Time resolved crystallography methods.


Enzymes are usually very specific as to which reactions they catalyze and the substrates that are involved in these reactions. Complementary shape, charge and hydrophilic/hydrophobic characteristics of enzymes and substrates are responsible for this specificity. Enzymes can also show impressive levels of stereospecificity, regioselectivity and chemoselectivity.[23]

Some of the enzymes showing the highest specificity and accuracy are involved in the copying and expression of the genome. These enzymes have "proof-reading" mechanisms. Here, an enzyme such as DNA polymerase catalyzes a reaction in a first step and then checks that the product is correct in a second step.[24] This two-step process results in average error rates of less than 1 error in 100 million reactions in high-fidelity mammalian polymerases.[25] Similar proofreading mechanisms are also found in RNA polymerase,[26] aminoacyl tRNA synthetases[27] and ribosomes.[28]

Whereas some enzymes have broad-specificity, as they can act on a relatively broad range of different physiologically relevant substrates, many enzymes possess small side activities which arose fortuitously (i.e. neutrally), which may be the starting point for the evolutionary selection of a new function; this phenomenon is known as enzyme promiscuity.[29]

"Lock and key" model

Enzymes are very specific, and it was suggested by Emil Fischer in 1894 that this was because both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another.[30] This is often referred to as "the lock and key" model. However, while this model explains enzyme specificity, it fails to explain the stabilization of the transition state that enzymes achieve.

Diagrams to show the induced fit hypothesis of enzyme action

In 1958, Daniel Koshland suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continuously reshaped by interactions with the substrate as the substrate interacts with the enzyme.[31] As a result, the substrate does not simply bind to a rigid active site; the amino acid 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.[32] The active site continues to change until the substrate is completely bound, at which point the final shape and charge is determined.[33] Induced fit may enhance the fidelity of molecular recognition in the presence of competition and noise via the conformational proofreading mechanism.[34]

Based on Fischer's lock-and-key model and Koshland’s induced fit theory, the Chou’s distorted key theory for peptide drugs was proposed [35] to develop peptide drugs against HIV/AIDS and SARS. [36] [37] [38]


Enzymes can act in several ways, all of which lower ΔG (Gibbs energy):[39]

  • Lowering the activation energy by creating an environment in which the transition state is stabilized (e.g. straining the shape of a substrate—by binding the transition-state conformation of the substrate/product molecules, the enzyme distorts the bound substrate(s) into their transition state form, thereby reducing the amount of energy required to complete the transition).
  • Lowering the energy of the transition state, but without distorting the substrate, by creating an environment with the opposite charge distribution to that of the transition state.
  • Providing an alternative pathway. For example, temporarily reacting with the substrate to form an intermediate ES complex, which would be impossible in the absence of the enzyme.
  • Reducing the reaction entropy change by bringing substrates together in the correct orientation to react. Considering ΔH alone overlooks this effect.
  • Increases in temperatures speed up reactions. Thus, temperature increases help the enzyme function and develop the end product even faster. However, if heated too much, the enzyme's shape deteriorates and the enzyme becomes denatured. Some enzymes like thermolabile enzymes work best at low temperatures.
  • The function of a protein is dependent on its structure so that if the structure is disrupted, so is its function.

It is interesting that this entropic effect involves destabilization of the ground state,[40] and its contribution to catalysis is relatively small.[41]

Transition state stabilization

The understanding of the origin of the reduction of ΔG requires one to find out how the enzymes can stabilize its transition state more than the transition state of the uncatalyzed reaction. It seems that the most effective way for reaching large stabilization is the use of electrostatic effects, in particular, when having a relatively fixed polar environment that is oriented toward the charge distribution of the transition state.[42] Such an environment does not exist in the uncatalyzed reaction in water.

Dynamics and function

The internal dynamics of enzymes has been suggested to be linked with their mechanism of catalysis.[43][44][45] Internal dynamics are the movement of parts of the enzyme's structure, such as individual amino acid residues, a group of amino acids, or even an entire protein domain. These movements occur at various time-scales ranging from femtoseconds to seconds. Networks of protein residues throughout an enzyme's structure can contribute to catalysis through dynamic motions.[46][47][48][49] This is simply seen in the kinetic scheme of the combined process, enzymatic activity and dynamics; this scheme can have several independent Michaelis-Menten-like reaction pathways that are connected through fluctuation rates.[50][51][52]

Protein motions are vital to many enzymes, but whether small and fast vibrations, or larger and slower conformational movements are more important depends on the type of reaction involved. However, although these movements are important in binding and releasing substrates and products, it is not clear if protein movements help to accelerate the chemical steps in enzymatic reactions.[53] These new insights also have implications in understanding allosteric effects and developing new medicines.

Allosteric modulation

Allosteric transition of an enzyme between R and T states, stabilized by an agonist, an inhibitor and a substrate (the MWC model)
Main article: Allosteric regulation

Allosteric sites are sites on the enzyme that bind to molecules in the cellular environment. The sites form weak, noncovalent bonds with these molecules, causing a change in the conformation of the enzyme. This change in conformation translates to the active site, which then affects the reaction rate of the enzyme.[54] Allosteric interactions can both inhibit and activate enzymes and are a common way that enzymes are controlled in the body.[55]

Cofactors and coenzymes


Some enzymes do not need any additional components to show full activity. However, others require non-protein molecules called cofactors to be bound for activity.[56] Cofactors can be either inorganic (e.g., metal ions and iron-sulfur clusters) or organic compounds (e.g., flavin and heme). Organic cofactors can be either prosthetic groups, which are tightly bound to an enzyme, or coenzymes, which are released from the enzyme's active site during the reaction. Coenzymes include NADH, NADPH and adenosine triphosphate. These molecules transfer chemical groups between enzymes.[57]

An example of an enzyme that contains a cofactor is carbonic anhydrase, and is shown in the ribbon diagram above with a zinc cofactor bound as part of its active site.[58] These tightly bound molecules are usually found in the active site and are involved in catalysis. For example, flavin and heme cofactors are often involved in redox reactions.

Enzymes that require a cofactor but do not have one bound are called apoenzymes or apoproteins. An apoenzyme together with its cofactor(s) is called a holoenzyme (this is the active form). Most cofactors are not covalently attached to an enzyme, but are very tightly bound. However, organic prosthetic groups can be covalently bound (e.g., biotin in the enzyme pyruvate carboxylase). The term "holoenzyme" can also be applied to enzymes that contain multiple protein subunits, such as the DNA polymerases; here the holoenzyme is the complete complex containing all the subunits needed for activity.


Space-filling model of the coenzyme NADH

Coenzymes are small organic molecules that can be loosely or tightly bound to an enzyme. Tightly bound coenzymes can be called prosthetic groups. Coenzymes transport chemical groups from one enzyme to another.[59] Some of these chemicals such as riboflavin, thiamine and folic acid are vitamins (compounds that cannot be synthesized by the body and must be acquired from the diet). The chemical groups carried include the hydride ion (H-) carried by NAD or NADP+, the phosphate group carried by adenosine triphosphate, the acetyl group carried by coenzyme A, formyl, methenyl or methyl groups carried by folic acid and the methyl group carried by S-adenosylmethionine.

Since coenzymes are chemically changed as a consequence of enzyme action, it is useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different enzymes. For example, about 700 enzymes are known to use the coenzyme NADH.[60]

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 even small amounts of coenzymes are used very intensively. For example, the human body turns over its own weight in ATP each day.[61]


The energies of the stages of a chemical reaction. Substrates need a lot of potential energy to reach a transition state, which then decays into products. The enzyme stabilizes the transition state, reducing the energy needed to form products.

As all catalysts, enzymes do not alter the position of the chemical equilibrium of the reaction. Usually, in the presence of an enzyme, the reaction runs in the same direction as it would without the enzyme, just more quickly. However, in the absence of the enzyme, other possible uncatalyzed, "spontaneous" reactions might lead to different products, because in those conditions this different product is formed faster.

Furthermore, enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive" a thermodynamically unfavorable one. For example, the hydrolysis of ATP is often used to drive other chemical reactions.[62]

Enzymes catalyze the forward and backward reactions equally. They do not alter the equilibrium itself, but only the speed at which it is reached. For example, carbonic anhydrase catalyzes its reaction in either direction depending on the concentration of its reactants.

\mathrm{CO_2 + H_2O \xrightarrow{Carbonic\ anhydrase}
H_2CO_3} (in tissues; high CO2 concentration)
\mathrm{H_2CO_3 \xrightarrow{Carbonic\ anhydrase}
CO_2 + H_2O} (in lungs; low CO2 concentration)

Nevertheless, if the equilibrium is greatly displaced in one direction, that is, in a very exergonic reaction, the reaction is in effect irreversible. Under these conditions, the enzyme will, in fact, catalyze the reaction only in the thermodynamically allowed direction.


Main article: Enzyme kinetics
Mechanism for a single substrate enzyme catalyzed reaction. The enzyme (E) binds a substrate (S) and produces a product (P).

Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products. The rate data used in kinetic analyses are commonly obtained from enzyme assays, where since the 90s, the dynamics of many enzymes are studied on the level of individual molecules.

In 1902 Victor Henri proposed a quantitative theory of enzyme kinetics,[63] but his experimental data were not useful because the significance of the hydrogen ion concentration was not yet appreciated. After Peter Lauritz Sørensen had defined the logarithmic pH-scale and introduced the concept of buffering in 1909[64] the German chemist Leonor Michaelis and his Canadian postdoc Maud Leonora Menten repeated Henri's experiments and confirmed his equation, which is referred to as Henri-Michaelis-Menten kinetics (termed also Michaelis-Menten kinetics).[65] Their work was further developed by G. E. Briggs and J. B. S. Haldane, who derived kinetic equations that are still widely considered today a starting point in solving enzymatic activity.[66]

The major contribution of Henri 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 complex. The enzyme then catalyzes the chemical step in the reaction and releases the product. Note that the simple Michaelis Menten mechanism for the enzymatic activity is considered today a basic idea, where many examples show that the enzymatic activity involves structural dynamics. This is incorporated in the enzymatic mechanism while introducing several Michaelis Menten pathways that are connected with fluctuating rates.[50][51][52] Nevertheless, there is a mathematical relation connecting the behavior obtained from the basic Michaelis Menten mechanism (that was indeed proved correct in many experiments) with the generalized Michaelis Menten mechanisms involving dynamics and activity; [67] this means that the measured activity of enzymes on the level of many enzymes may be explained with the simple Michaelis-Menten equation, yet, the actual activity of enzymes is richer and involves structural dynamics.

Saturation curve for an enzyme reaction showing the relation between the substrate concentration (S) and rate (v)

Enzymes can catalyze up to several million reactions per second. For example, the uncatalyzed decarboxylation of orotidine 5'-monophosphate has a half life of 78 million years. However, when the enzyme orotidine 5'-phosphate decarboxylase is added, the same process takes just 25 milliseconds.[68] Enzyme rates depend on solution conditions and substrate concentration. Conditions that denature the protein abolish enzyme activity, such as high temperatures, extremes of pH or high salt concentrations, while raising substrate concentration tends to increase activity when [S] is low. 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 form. At the maximum reaction rate (Vmax) 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. However, Vmax is only one kinetic constant of enzymes. The amount of substrate needed to achieve a given rate of reaction is also important. This is given by the Michaelis-Menten constant (Km), which is the substrate concentration required for an enzyme to reach one-half its maximum reaction rate; generally, each enzyme has a characteristic Km for a given substrate. Another useful constant is kcat, which is the rate of product formation handled by one active site and is generally given in units of inverse seconds.


Michaelis-Menten kinetics relies on the law of mass action, which is derived from the assumptions of free diffusion and thermodynamically driven random collision. However, many biochemical or cellular processes deviate significantly from these conditions, because of macromolecular crowding, phase-separation of the enzyme/substrate/product, or one or two-dimensional molecular movement.[69] In these situations, a fractal Michaelis-Menten kinetics may be applied.[70][71][72][73]

Some enzymes operate with kinetics, which are faster than diffusion rates, which would seem to be impossible. Several mechanisms have been invoked to explain this phenomenon. Some proteins are believed to accelerate catalysis by drawing their substrate in and pre-orienting them by using dipolar electric fields. Other models invoke a quantum-mechanical tunneling explanation, whereby a proton or an electron can tunnel through activation barriers, although for proton tunneling this model remains somewhat controversial.[74][75] Quantum tunneling for protons has been observed in tryptamine.[76] This suggests that enzyme catalysis may be more accurately characterized as "through the barrier" rather than the traditional model, which requires substrates to go "over" a lowered energy barrier.


Competitive inhibitors bind reversibly to the enzyme, preventing the binding of substrate. On the other hand, binding of substrate prevents binding of the inhibitor. Substrate and inhibitor compete for the enzyme.
Types of inhibition. This classification was introduced by W.W. Cleland.[77]
Main article: Enzyme inhibitor


Competitive inhibition

In competitive inhibition, the inhibitor and substrate compete for the enzyme (i.e., they can not bind at the same time).[78] Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, methotrexate is a competitive inhibitor of the enzyme dihydrofolate reductase, which catalyzes the reduction of dihydrofolate to tetrahydrofolate. The similarity between the structures of folic acid and this drug are shown in the figure to the right bottom. In some cases, the inhibitor can bind to a site other than the binding-site of the usual substrate and exert an allosteric effect to change the shape of the usual binding-site. For example, strychnine acts as an allosteric inhibitor of the glycine receptor in the mammalian spinal cord and brain stem. Glycine is a major post-synaptic inhibitory neurotransmitter with a specific receptor site. Strychnine binds to an alternate site that reduces the affinity of the glycine receptor for glycine, resulting in convulsions due to lessened inhibition by the glycine.[79] In competitive inhibition the maximal rate of the reaction is not changed, but higher substrate concentrations are required to reach a given maximum rate, increasing the apparent Km.

Uncompetitive inhibition

In uncompetitive inhibition, the inhibitor cannot bind to the free enzyme, only to the ES-complex. The EIS-complex thus formed is enzymatically inactive. This type of inhibition is rare, but may occur in multimeric enzymes.

Non-competitive inhibition

Non-competitive inhibitors can bind to the enzyme at the binding site at the same time as the substrate,but not to the active site. Both the EI and EIS complexes are enzymatically inactive. Because the inhibitor can not be driven from the enzyme by higher substrate concentration (in contrast to competitive inhibition), the apparent Vmax changes. But because the substrate can still bind to the enzyme, the Km stays the same.

Mixed inhibition

This type of inhibition resembles the non-competitive, except that the EIS-complex has residual enzymatic activity.This type of inhibitor does not follow Michaelis-Menten equation.

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. Enzymes that are subject to this form of regulation are often multimeric and have allosteric binding sites for regulatory substances. Their substrate/velocity plots are not hyperbolar, but sigmoidal (S-shaped).

The coenzyme folic acid (left) and the anti-cancer drug methotrexate (right) are very similar in structure. As a result, methotrexate is a competitive inhibitor of many enzymes that use folates.

Irreversible inhibitors react with the enzyme and form a covalent adduct with the protein. The inactivation is irreversible. These compounds include eflornithine a drug used to treat the parasitic disease sleeping sickness.[80] Penicillin and Aspirin also act in this manner. With these drugs, the compound is bound in the active site and the enzyme then converts the inhibitor into an activated form that reacts irreversibly with one or more amino acid residues.

Uses of inhibitors

Since inhibitors modulate the function of enzymes they are often used as drugs. A common example of an inhibitor that is used as a drug is aspirin, which inhibits the COX-1 and COX-2 enzymes that produce the inflammation messenger prostaglandin, thus suppressing pain and inflammation. However, 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.[81]

Biological function

Enzymes serve a wide variety of functions inside living organisms. They are indispensable for signal transduction and cell regulation, often via kinases and phosphatases.[82] They also generate movement, with myosin hydrolyzing ATP to generate muscle contraction and also moving cargo around the cell as part of the cytoskeleton.[83] Other ATPases in the cell membrane are ion pumps involved in active transport. Enzymes are also involved in more exotic functions, such as luciferase generating light in fireflies.[84] Viruses 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.


Glycolytic enzymes and their functions in the metabolic pathway of glycolysis


Enzymes determine what steps occur in these pathways. Without enzymes, metabolism would neither progress through the same steps nor be fast enough to serve the needs of the cell. Indeed, a metabolic pathway such as glycolysis could not exist independently of enzymes. Glucose, for example, can react directly with ATP to become phosphorylated at one or more of its carbons. In the absence of enzymes, this occurs so slowly as to be insignificant. However, if hexokinase is added, these slow reactions continue to take place except that phosphorylation at carbon 6 occurs so rapidly that, if the mixture is tested a short time later, glucose-6-phosphate is found to be the only significant product. As a consequence, the network of metabolic pathways within each cell depends on the set of functional enzymes that are present.

Control of activity


  1. Enzyme production (transcription and translation of enzyme genes) can be enhanced or diminished by a cell in response to changes in the cell's environment. This form of gene regulation is called enzyme induction and inhibition. For example, bacteria may become resistant to antibiotics such as penicillin because enzymes called beta-lactamases are induced that hydrolyze the crucial beta-lactam ring within the penicillin molecule. Another example are enzymes in the liver called cytochrome P450 oxidases, which are important in drug metabolism. Induction or inhibition of these enzymes can cause drug interactions.
  2. Enzymes can be compartmentalized, with different metabolic pathways occurring in different cellular compartments. For example, fatty acids are synthesized by one set of enzymes in the cytosol, endoplasmic reticulum and the Golgi apparatus and used by a different set of enzymes as a source of energy in the mitochondrion, through β-oxidation.[86]
  3. Enzymes can be regulated by inhibitors and activators. For example, the end product(s) of a metabolic pathway are often inhibitors for one of the first enzymes of the pathway (usually the first irreversible step, called committed step), thus regulating the amount of end product made by the pathways. Such a regulatory mechanism is called a negative feedback mechanism, because the amount of the end product produced is regulated by its own concentration. Negative feedback mechanisms can effectively adjust the rate of synthesis of intermediate metabolites according to the demands of the cells. This helps allocate materials and energy economically, and prevents the manufacture of excess end products. The control of enzymatic action helps to maintain a stable internal environment in living organisms.
  4. Enzymes can be regulated through covalent modulation. This can 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.[87] 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 duodenum 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.
  5. Some enzymes may become activated when localized to a different environment (e.g., from a reducing (cytoplasm) to an oxidizing (periplasm) environment, high pH to low pH, etc.). For example, hemagglutinin in the influenza virus is activated by a conformational change caused by the acidic conditions, these occur when it is taken up inside its host cell and enters the lysosome.[88]

Involvement in disease


One example is the most common type of phenylketonuria. A mutation of a single amino acid in the enzyme phenylalanine hydroxylase, which catalyzes the first step in the degradation of phenylalanine, results in build-up of phenylalanine and related products. This can lead to intellectual disability if the disease is untreated.[89] Another example of enzyme deficiency is pseudocholinesterase[disambiguation needed], in which the body's ability to break down choline ester drugs is impaired.[90]

A further example is when germline mutations in genes coding for DNA repair enzymes cause hereditary cancer syndromes such as xeroderma pigmentosum. Defects in these enzymes cause cancer since the body is less able to repair mutations in the genome. This causes a slow accumulation of mutations and results in the development of many types of cancer in the sufferer.

Oral administration of enzymes can be used to treat several diseases (e.g. pancreatic insufficiency and lactose intolerance). Since enzymes are proteins themselves they are potentially subject to inactivation and digestion in the gastrointestinal environment. Therefore a non-invasive imaging assay was developed to monitor gastrointestinal activity of exogenous enzymes (prolyl endopeptidase as potential adjuvant therapy for celiac disease) in vivo.[91]

Naming conventions

An enzyme's name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase. Examples are lactase, alcohol dehydrogenase and DNA polymerase. This may result in different enzymes, called isozymes, with the same function having the same basic name. Isoenzymes have a different amino acid sequence and might be distinguished by their optimal pH, kinetic properties or immunologically. Isoenzyme and isozyme are homologous proteins. Furthermore, the normal physiological reaction an enzyme catalyzes may not be the same as under artificial conditions. This can result in the same enzyme being identified with two different names. For example, glucose isomerase, which is used industrially to convert glucose into the sweetener fructose, is a xylose isomerase in vivo (within the body).


The top-level classification is[92]

According to the naming conventions, enzymes are generally classified into six main family classes and many sub-family classes. Some web-servers, e.g., EzyPred [93] and bioinformatics tools have been developed to predict which main family class [94] and sub-family class [95] [96] an enzyme molecule belongs to according to its sequence information alone via the pseudo amino acid composition.

Industrial applications

Enzymes are used in the chemical industry and other industrial applications when extremely specific catalysts are required. However, enzymes in general are limited in the number of reactions they have evolved to catalyze and also by their lack of stability in organic solvents 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.[97][98] 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.[99]

Application Enzymes used Uses
Food processing
Amylases catalyze the release of simple sugars from starch.
Amylases from fungi and plants Production of sugars from starch, such as in making high-fructose corn syrup.[100] In baking, catalyze breakdown of starch in the flour to sugar. Yeast fermentation of sugar produces the carbon dioxide that raises the dough.
Proteases Biscuit manufacturers use them to lower the protein level of flour.
Baby foods Trypsin To predigest baby foods
Brewing industry
Germinating barley used for malt
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 for fermentation.
Industrially produced barley enzymes Widely used in the brewing process to substitute for the natural enzymes found in barley.
Betaglucanases and arabinoxylanases Improve the wort and beer filtration characteristics.
Amyloglucosidase and pullulanases Low-calorie beer and adjustment of fermentability.
Proteases Remove cloudiness produced during storage of beers.
Acetolactatedecarboxylase (ALDC) Increases fermentation efficiency by reducing diacetyl formation.[101]
Fruit juices Cellulases, pectinases Clarify fruit juices.
Dairy industry
Roquefort cheese
Rennin, derived from the stomachs of young ruminant animals (like calves and lambs) Manufacture of cheese, used to hydrolyze protein
Microbially produced enzyme Now finding increasing use in the dairy industry
Lipases Is implemented during the production of Roquefort cheese to enhance the ripening of the blue-mold cheese.
Lactases Break down lactose to glucose and galactose.
Meat tenderizers Papain To soften meat for cooking
Starch industry
Amylases, amyloglucosideases and glucoamylases Converts starch into glucose and various syrups.
Glucose isomerase Converts glucose into fructose in production of high-fructose syrups from starchy materials. These syrups have enhanced sweetening properties and lower calorific values than sucrose for the same level of sweetness.
Paper industry
A paper mill in South Carolina
Amylases, Xylanases, Cellulases and ligninases Degrade starch to lower viscosity, aiding sizing and coating paper. Xylanases reduce bleach required for decolorizing; cellulases smooth fibers, enhance water drainage, and promote ink removal; lipases reduce pitch and lignin-degrading enzymes remove lignin to soften paper.
Biofuel industry
Cellulose in 3D
Cellulases Used to break down cellulose into sugars that can be fermented (see cellulosic ethanol)
Ligninases Use of lignin waste
Biological detergent Primarily proteases, produced in an extracellular form from bacteria Used for presoak conditions and direct liquid applications helping with removal of protein stains from clothes
Amylases Detergents for machine dish washing to remove resistant starch residues
Lipases Used to assist in the removal of fatty and oily stains
Cellulases Used in biological fabric conditioners
Contact lens cleaners Proteases To remove proteins on contact lens to prevent infections
Rubber industry Catalase To generate oxygen from peroxide to convert latex into foam rubber
Photographic industry Protease (ficin) Dissolve gelatin off scrap film, allowing recovery of its silver content.
Molecular biology
Part of the DNA double helix
Restriction enzymes, DNA ligase and polymerases Used to manipulate DNA in genetic engineering, important in pharmacology, agriculture and medicine. Essential for restriction digestion and the polymerase chain reaction. Molecular biology is also important in forensic science.

See also


  1. ^ Smith AL (Ed) (1997). Oxford dictionary of biochemistry and molecular biology. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-854768-4. 
  2. ^ Grisham, Charles M.; Reginald H. Garrett (1999). Biochemistry. Philadelphia: Saunders College Pub. pp. 426–7. ISBN 0-03-022318-0. 
  3. ^ Bairoch A. (2000). "The ENZYME database in 2000" (PDF). Nucleic Acids Res 28 (1): 304–5. doi:10.1093/nar/28.1.304. PMC 102465. PMID 10592255. 
  4. ^ Lilley D (2005). "Structure, folding and mechanisms of ribozymes". Current Opinion in Structural Biology 15 (3): 313–23. doi:10.1016/j.sbi.2005.05.002. PMID 15919196. 
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