Enzyme

Ribbon diagram of the enzyme TIM. TIM is catalytically perfect, meaning its conversion rate is limited, or nearly limited, to its substrate diffusion rate.

Enzymes are proteins that accelerate, or catalyze, chemical reactions. In these reactions, the molecules at the beginning of the process are called substrates and the enzyme converts these into different molecules: the products. Almost all processes in the cell need enzymes in order to occur at significant rates. Since enzymes are extremely selective for their substrates and speed up only a few reactions from among many possibilities, the set of enzymes made in a cell determines which metabolic pathways occur in that cell.

Enzymes are known to catalyze about 4,000 reactions. However, not all biological catalysts are proteins, since some RNA molecules called ribozymes can also catalyze reactions. Enzymes are usually named according to the reaction they catalyze. Typically the suffix -ase is added to the name of the substrate (e.g., lactase is the enzyme that cleaves lactose) or the type of reaction (e.g., DNA polymerase forms DNA polymers).

Like all catalysts, enzymes work by providing an alternative path of lower activation energy for a reaction and dramatically accelerating its rate. Some enzymes can make their conversion of substrate to product occur many millions of times faster. For example, the reaction catalysed by orotidine 5'-phosphate decarboxylase will consume half of its substrate in 78 million years if no enzyme is present. However, when the decarboxylase is added, the same process takes just 25 milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, nor do they alter the equilibrium of a reaction. However, enzymes do differ from most other catalysts by being much more specific.

Enzyme activity can be affected by other molecules. Inhibitors are molecules that decrease enzyme activity, and activators are molecules that increase activity. Drugs and poisons are often enzyme inhibitors.

Some enzymes are used commercially, for example, in the synthesis of antibiotics. In addition, some household cleaning products use enzymes to speed up chemical reactions (e.g., enzymes in biological washing powders break down protein or fat stains on clothes).

Etymology and history

In the 19th century, when studying the fermentation of food of sugar to alcohol by yeast, Louis Pasteuur 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 organisation of the yeast cells, not with the death or putrefaction of the cells. "

Structures and mechanisms

Ribbon-diagram showing the active sites of Carbonic anhydrase. The grey spheres are the zinc ions in the four active sites of this carbonic anhydrase enzyme and are held within two protein chains. Diagram drawn from PDB 1DDZ.

The activities of enzymes are determined by their [[quaternary structure|

Most enzymes are much larger than the substrates they act on, and only a very small portion of the enzyme (around 3–4 amino acids is directly involved in catalysis). 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 substrate to the active sites and are known as Cofactor.these are inorganic in nature and are must for catalysis.

Like all proteins, enzymes are made as long, linear chains of amino acids to produce a tertiary structure. Each unique amino acid sequence produces a unique structure, which has unique properties. Individual protein chains may sometimes group together to form a protein complex. Most enzymes can become unfolded and inactivated—by heating which destroys the Tertiary structure of the protein. Depending on the enzyme, denaturation may be reversible or irreversible.

Specificity

Enzymes are usually specific as to which reactions they catalyze. Shape, charge complementarity, and hydrophilic/hydrophobic characters of enzymes and substrates are responsible for this specificity. Enzymes can also show impressive levels of stereospecificity, regioselectivity and chemoselectivity.

Dynamics and function

Recent investigations have provided new insights into the connection between internal dynamics of enzymes and their mechanism of catalysis.An enzyme's internal dynamics are described as the movement of internal parts (e.g. amino acids, a group of amino acids, a loop region, an alpha helix, neighboring beta-sheets or even entire domain) of these biomolecules, which can occur at various time-scales ranging from femtoseconds to seconds. Networks of protein residues throughout an enzyme's structure can contribute to catalysis through dynamic motions. Protein motions are vital to many enzymes, but whether small and fast vibrations or larger and slower conformational movements are more important depends on the type of reaction involved. These new insights also have implications in understanding allosteric effects, producing designer enzymes and developing new drugs. 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. An apoenzyme together with its cofactor(s) is called a holoenzyme (i.e., the active form). Most cofactors are not covalently attached to an enzyme, but are very tightly bound. However, organic prosthetic groups can be covalently bound (e.g., thiamine pyrophosphate in the enzyme pyruvate dehydrogenase).

Coenzymes

Space-filling model of the coenzyme NADH

Coenzymes are small molecules that transport chemical groups from one enzyme to another. Some of these chemicals such as riboflavin, thiamine and folic acid are vitamins, this is when these compounds cannot be made in the body and must be acquired from the diet. The chemical groups carried include the hydride ion (H+ + 2e-) carried by NAD or NADP⁺, the acetyl group carried by coenzyme A, formyl, methenyl or methyl groups carried by folic acid and the methyl group carried by S-adenosylmethionine.

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

Coenzymes are usually regenerated and their concentrations maintained at a steady level inside the cell: for example, NADPH is regenerated through the pentose phosphate pathway and S-adenosylmethionine by methionine adenosyltransferase.

Thermodynamics

Main articles: Activation energy, Thermodynamic equilibrium, and Chemical equilibrium

File:Activation2.svg

Diagram of a catalytic reaction, showing the energy niveau at each stage of the reaction. The substrates usually need a large amount of energy to reach the transition state, which then decays into the end product. The enzyme stabilizes the transition state, reducing the energy needed to form this species and thus reducing the energy required to form products.

As with all catalysts, all reactions catalyzed by enzymes must be "spontaneous" (containing a net negative Gibbs free energy). In the presence of an enzyme, a reaction runs in the same direction as it would without the enzyme, just more quickly. However, the uncatalyzed, "spontaneous" reaction might lead to different products than the catalyzed reaction. Furthermore, enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive" a thermodynamically unfavorable one. For example, the cleavage of the high-energy compound ATP is often used to drive other energetically unfavorable chemical reactions.

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

$\mathrm {CO_{2}+H_{2}O{}^{\mathrm {\quad Carbonic\ anhydrase} }\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!{\overrightarrow {\qquad \qquad \qquad \qquad }}H_{2}CO_{3}}$ (in tissues; high CO₂ concentration)

$\mathrm {H_{2}CO_{3}{}^{\mathrm {\quad Carbonic\ anhydrase} }\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!\!{\overrightarrow {\qquad \qquad \qquad \qquad }}CO_{2}+H_{2}O}$ (in lungs; low CO₂ concentration)

Nevertheless, if the physiological concentrations of the substrates and products have a large negative Gibbs free energy (exergonic), then the reaction is effectively irreversible. Under these conditions it is possible that the enzyme will only catalyze the reaction in one direction.

Kinetics

Main 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 obtained from enzyme assays. 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 kinetic equations that are still widely used today.

The major contribution of Michaelis and Menten was to think of enzyme reactions in two stages. In the first, the substrate binds reversibly to the enzyme, forming the enzyme-substrate complex. This is sometimes called the Michaelis-Menten complex in their honor. The enzyme then catalyzes the chemical step in the reaction and releases the product.

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

Enzymes can catalyze up to several million reactions per second. To find the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is seen. This is shown in the saturation curve, shown on the right. Saturation happens because, as substrate concentration increases, more and more of the free enzyme is converted into the substrate-bound ES form. At the maximum velocity (V_max) of the enzyme, all enzyme active sites are saturated with substrate, and the amount of ES complex is the same as the total amount of enzyme.

However, V_max is only one kinetic constant of enzymes. The amount of substrate needed to achieve a given rate of reaction is also important. This is given by the Michaelis-Menten constant (K_m), which is the substrate concentration required for an enzyme to reach one-half its maximum velocity. Each enzyme has a characteristic K_m for a given substrate, and this can show how tight the binding of the substrate is to the enzyme. Another useful constant is k_cat, which is the number of substrate molecules handled by one active site per second.

The efficiency of an enzyme can be expressed in terms of k_cat/K_m. This is also called the specificity constant and incorporates the rate constants for all steps in the reaction. Because the specificity constant reflects both affinity and catalytic ability, it is useful for comparing different enzymes against each other, or the same enzyme with different substrates. The theoretical maximum for the specificity constant is called the diffusion limit and is about 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 with this property are called catalytically perfect or kinetically perfect. Example of such enzymes are triose-phosphate isomerase, carbonic anhydrase, acetylcholinesterase, catalase, fumarase, ß-lactamase, and superoxide dismutase.

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

Inhibition

A competitive inhibitor binds reversibly to the enzyme, preventing the binding of substrate. On the other hand, binding of substrate prevents binding of the inhibitor. Substrate and inhibitor compete for the enzyme.

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

Main article: Enzyme inhibition

Enzymes reaction rates can be decreased by various types of enzyme inhibitors.

Reversible inhibitors

Competitive inhibition

In competitive inhibition the inhibitor binds to the substrate binding site as shown (right top), thus preventing substrate from binding (EI complex). Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, methotrexate is a competitive inhibitor of the enzyme dihydrofolate reductase, which catalyzes the reduction of dihydrofolate to tetrahydrofolate. The similarity between the structures of folic acid and this drug are shown on the right.

Non-competitive inhibition

Non-competitive inhibitors never bind to the active site, but to other parts of the enzyme that can be far away from the substrate binding site (right, bottom). Moreover, non-competitive inhibitors only bind to the enzyme-substrate (ES) complex and not to free enzyme. Their binding to this site changes the shape of the enzyme and stops the active site binding substrate(s). Consequently, since there is no direct competition between the substrate and inhibitor for the enzyme, the extent of inhibition depends only on the inhibitor concentration and will not be affected by the substrate concentration.

Irreversible inhibitors

Some enzyme inhibitors react with the enzyme and form a covalent adduct with the protein. The inactivation produced by this type of inhibitor cannot be reversed. A class of these compounds called Suicide inhibitors includes eflornithine a drug used to treat the parasitic disease sleeping sickness.

Uses of inhibitors

Inhibitors are often used as drugs, but they can also act as poisons. However, the difference between a drug and a poison is usually only a matter of amount, since most drugs are toxic at some level, as Paracelsus wrote, "In all things there is a poison, and there is nothing without a poison." Equally, antibiotics and other anti-infective drugs are just specific poisons that can kill a pathogen but not its host.

An example of an inhibitor being used as a drug is aspirin, which inhibits the COX-1 and COX-2 enzymes that produce the inflammation messenger prostaglandin, thus suppressing pain and inflammation. The poison cyanide is an irreversible enzyme inhibitor that combines with the copper prosthetic groups of the enzyme cytochrome c oxidase and blocks cellular respiration.

In many organisms inhibitors may act as part of a feedback mechanism. If an enzyme produces too much of one substance in the organism, that substance may act as an inhibitor for the enzyme that produces it, causing production of the substance to slow down or stop when there is sufficient amount. This is a form of negative feedback.

Biological function

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

Viruses can contain enzymes for infecting cells, such as the HIV integrase and reverse transcriptase, or for viral release from cells, like the influenza virus neuraminidase.

Metabolism

Several enzymes can work together in a specific order, creating metabolic pathways. In a metabolic pathway, one enzyme takes the product of another enzyme as a substrate. After the catalytic reaction, the product is then passed on to another enzyme. Sometimes more than one enzyme can catalyse the same reaction in parallel, this can allow more complex regulation: with for example a low contant activity being provided by one enzyme but an inducible high activity from a second enzyme.

Enzymes determine what steps occur in these pathways. Without enzymes, metabolism would neither progress through the same steps, nor be fast enough to serve the needs of the cell. Indeed, a metabolic pathway such as glycolysis could not exist independently of enzymes. Glucose, for example, can react directly with ATP to become phosphorylated at one or more of its carbons. However, if hexokinase is present, glucose-6-phosphate is the only product, as this reaction will occur most swiftly. Consequently, the network of metabolic pathways within each cell depends on the set of functional enzymes that are present.

Control of activity

There are four main ways that enzyme activity is controlled in the cell.

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 hydrolyse 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.
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 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 homeostatic devices, the control of enzymatic action helps to maintain a stable internal environment in living organisms.
4. Enzymes can be regulated through post-translational modification. 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. Another example of post-translational modification is the cleavage of the polypeptide chain. Chymotrypsin, a digestive protease, is produced in inactive form as chymotrypsinogen in the pancreas and transported in this form to the stomach where it is activated. This stops the enzyme from digesting the pancreas or other tissues before it enters the gut. This type of inactive precursor to an enzyme is known as a zymogen.

Involvement in disease

Phenylalanine hydroxylase. Created from PDB 1KW0

Since the tight control of enzyme activity is essential for homeostasis, any malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a genetic disease. The importance of enzymes is shown by the fact that a lethal illness can be caused by the malfunction of just one type of enzyme out of the thousands of types present in our bodies.

One example is the most common type of phenylketonuria. Mutation of this gene causes a single amino acid change in the enzyme phenylalanine hydroxylase, which catalyzes the first step in the degradation of phenylalanine. The resulting build-up of phenylalanine and related products can lead to mental retardation if the disease is untreated.

Another 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.

Naming conventions

An enzyme's name is a description of what it does, with the word ending in -ase. Examples are alcohol dehydrogenase and DNA polymerase. Kinases are enzymes that transfer phosphate groups. This results in different enzymes with the same function having the same basic name; they are therefore distinguished by other characteristics, such as their optimal pH (alkaline phosphatase) or their location (membrane ATPase). Furthermore, the reversibility of chemical reactions means that the normal physiological direction of an enzyme reaction may not be seen under laboratory conditions. This can result in the same enzyme being identified with two different names: one coming from the laboratory identification and the other from its behavior in the cell. For instance, the enzyme formally known as xylitol:NAD+ 2-oxidoreductase (D-xylulose-forming) is more commonly referred to from the cellular viewpoint as D-xylulose reductase, since the function of the enzyme in the cell is actually the reverse of what is often seen under laboratory conditions.

The International Union of Biochemistry and Molecular Biology and the International Union of Pure and Applied Chemistry have developed a nomenclature for enzymes, the EC numbers; each enzyme is described by a sequence of four numbers preceded by "EC". However, this is not a perfect solution, as enzymes from different species or even very similar enzymes in the same species may have identical EC numbers.

The first number broadly classifies the enzyme based on its mechanism:

The top-level classification is

• EC 1 Oxidoreductases: catalyze oxidation/reduction reactions
• EC 2 Transferases: transfer a functional group (e.g. a methyl or phosphate group)
• EC 3 Hydrolases: catalyze the hydrolysis of various bonds
• EC 4 Lyases: cleave various bonds by means other than hydrolysis and oxidation
• EC 5 Isomerases: catalyze isomerization changes within a single molecule
• EC 6 Ligases: join two molecules with covalent bonds

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

Industrial applications

Enzymes are used in the chemical industry and other industrial applications when extremely specific catalysts are required. However, enzymes in general are limited in the number of reactions they have evolved to catalyse and also by their lack of stability in organic solvents and at high temperatures. Consequently, protein engineering is an active area of research and involves attempts to create new enzymes with novel properties, either through rational design or in vitro evolution.

Application	Enzymes used	Uses
Biological detergent File:Washingpowder.jpg	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.
Baking industry alpha-amylase catalyzes the release of sugar monomers from starch	Fungal alpha-amylase enzymes are normally inactivated at about 50 degrees Celsius, but are destroyed during the 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.
	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.
	Amylase, glucanases, proteases	Split polysaccharides and proteins in the malt.
	Betaglucosidase	Improve the filtration characteristics.
	Amyloglucosidase	Low-calorie beer.
	Proteases	Remove cloudiness produced during storage of beers.
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-mould cheese.
	Lactases	Break down lactose to glucose and galactose.
Starch industry	Amylases, amyloglucosideases and glucoamylases	Converts starch into glucose and various syrups.
	Glucose isomerase	Converts glucose into fructose (high fructose syrups derived from starchy materials have enhanced sweetening properties and lower calorific values).
Rubber industry	Catalase	To generate oxygen from peroxide to convert latex into foam rubber.
Paper industry File:InternationalPaper6413.JPG A paper mill in South Carolina.	Amylases, Xylanases, Cellulases and ligninases	Degrade starch to a lower viscosity product needed for sizing and coating paper. Xylanases reduce the amount of bleach required for decolorising; cellulases smooth fibers, enhance water drainage, and promote ink removal; lipases reduce pitch and lignin-degrading enzymes remove lignin from pulps to soften paper.
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

• Enzyme kinetics
• Enzyme inhibitor
• Enzyme assay

Further reading

Etymology and history

• New Beer in an Old Bottle: Eduard Buchner and the Growth of Biochemical Knowledge, edited by Athel Cornish-Bowden and published by Universitat de València (1997): ISBN 84-370-3328-4, A history of early enzymology.
• Williams, Henry Smith, 1863-1943. A History of Science: in Five Volumes. Volume IV: Modern Development of the Chemical and Biological Sciences, A textbook from the 19th century.
• Kleyn, J. and Hough J. The Microbiology of Brewing. Annual Review of Microbiology (1971) Vol. 25: 583-608

Enzyme structure and mechanism

• Fersht, A. Structure and Mechanism in Protein Science : A Guide to Enzyme Catalysis and Protein Folding. W. H. Freeman, 1998 ISBN 0-7167-3268-8
• Walsh, C., Enzymatic Reaction Mechanisms. W. H. Freeman and Company. 1979. ISBN 0-7167-0070-0
• Page, M. I., and Williams, A. (Eds.), 1987. Enzyme Mechanisms. Royal Society of Chemistry. ISBN 0-85186-947-5
• M.V. Volkenshtein, R.R. Dogonadze, A.K. Madumarov, Z.D. Urushadze, Yu.I. Kharkats. Theory of Enzyme Catalysis.- Molekuliarnaya Biologia, (1972), 431-439 (In Russian, English summary)
• Warshel, A., Computer Modeling of Chemical Reactions in enzymes and Solutions John Wiley & Sons Inc. 1991. ISBN 0-471-18440-3

Thermodynamics

• Reactions and Enzymes Chapter 10 of On-Line Biology Book at Estrella Mountain Community College.

Kinetics and Inhibition

• Athel Cornish-Bowden, Fundamentals of Enzyme Kinetics. (3rd edition), Portland Press (2004), ISBN 1-85578-158-1.
• Irwin H. Segel, Enzyme Kinetics : Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems. Wiley-Interscience; New Ed edition (1993), ISBN 0-471-30309-7.
• John W. Baynes, Medical Biochemistry, Elsevier-Mosby; 2th Edition (2005), ISBN 0-7234-3341-0, p. 57.

Function and control of enzymes in the cell

• Price, N. and Stevens, L., Fundamentals of Enzymology: Cell and Molecular Biology of Catalytic Proteins Oxford University Press, (1999), ISBN 0-19-850229-X
• Nutritional and Metabolic Diseases

Enzyme-naming conventions

• Enzyme Nomenclature, Recommendations for enzyme names from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology.
• Koshland D. The Enzymes, v. I, ch. 7, Acad. Press, New York, (1959)

Industrial Applications

• History of industrial enzymes, Article about the history of industrial enzymes, from the late 1900's to the present times.

External links

• Structure/Function of Enzymes, Web tutorial on enzyme structure and function.
• Enzyme spotlight Monthly feature at the European Bioinformatics Institute on a selected enzyme.
• AMFEP, Association of Manufacturers and Formulators of Enzyme Products
• ExPASy enzyme database, links to Swiss-Prot sequence data, entries in other databases and to related literature searches.
• Enzyme Structures Database links to the known 3-D structure data of enzymes in the Protein Data Bank.
• MACiE, database of enzyme reaction mechanisms.
• BRENDA, comprehensive compilation of information and literature references about all known enzymes; requires payment by commercial users.
• KEGG: Kyoto Encyclopedia of Genes and Genomes Graphical and hypertext-based information on biochemical pathways and enzymes.
• 'Face-to-Face Interview with Sir John Cornforth who was awarded a Noble Prize for work on stereochemistry of enzyme-catalyzed reactions Freeview video by the Vega Science Trust