Proteins and Enzymes

A representation of the 3D structure of myoglobin, showing coloured alpha helices. This protein was the first to have its structure solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, which led to their receiving a Nobel Prize in Chemistry.

A protein (from the Greek "protos" meaning "of primary importance") is a complex, high-molecular-weight organic compound that consists of amino acids joined by peptide bonds. Proteins are essential to the structure and function of all living cells and viruses. Many proteins are enzymes or subunits of enzymes. Other proteins play structural or mechanical roles, such as those that form the struts and joints of the cytoskeleton, serving as biological scaffolds for the mechanical integrity and tissue signalling functions. Still more functions filled by proteins include immune response and the storage and transport of various ligands. In nutrition, proteins are broken down through digestion to provide amino acids for the organism, including those the organism may not be able to synthesise itself.

Proteins are one of the classes of bio-macromolecules, alongside polysaccharides, lipids, and nucleic acids, that make up the primary constituents of living things. They are among the most actively-studied molecules in biochemistry, and were discovered by Jöns Jakob Berzelius in 1838.

The coding sequences of genes determine the amino-acid sequences of almost all naturally occuring proteins, via the processes of transcription and translation. In many cases, the resulting protein is then chemically altered (post-translational modification), before becomming functional. It is very common for proteins to work together to achieve a particuar function, and often physically associate with one another to form a complex.

Properties of Protein

Structure

Example of 3-dimensional structure of protein

Main article: Protein structure

Proteins are amino acid chains that fold into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its native state, which is determined by its sequence of amino acids. Thus, proteins are their own polymers, with amino acids being the monomers. Biochemists refer to four distinct aspects of a protein's structure:

• Primary structure: the amino acid sequence
• Secondary structure: highly patterned sub-structures—alpha helix and beta sheet—or segments of chain that assume no stable shape. Secondary structures are locally defined, meaning that there can be many different secondary motifs present in one single protein molecule.
• Tertiary structure: the overall shape of a single protein molecule; the spatial relationship of the secondary structural motifs to one another
• Quaternary structure: the shape or structure that results from the union of more than one protein molecule, usually called protein subunits in this context, which function as part of the larger assembly or protein complex.

In addition to these levels of structure, proteins may shift between several similar structures in performing their biological function. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as "conformations," and transitions between them are called conformational changes.

The primary structure is held together by covalent peptide bonds, which are made during the process of translation. The secondary structures are held together by hydrogen bonds. The tertiary structure is held together primarily by hydrophobic interactions but hydrogen bonds, ionic interactions, and disulfide bonds are usually involved too.

The process by which the higher structures form is called protein folding and is a consequence of the primary structure. The mechanism of protein folding is not entirely understood. Although any unique polypeptide may have more than one stable folded conformation, each conformation has its own biological activity and only one conformation is considered to be the active, or native conformation.

The two ends of the amino acid chain are referred to as the carboxy terminus (C-terminus) and the amino terminus (N-terminus) based on the nature of the free group on each extremity.

Working with proteins

Proteins are sensitive to their environment. They may only be active in their native state, over a small pH range, and under solution conditions with a minimum quantity of electrolytes. A protein in its native state is often described as folded. A protein that is not in its native state is said to be denatured. Denatured proteins generally have no well-defined secondary structure. Many proteins denature and will not remain in solution in distilled water.

One of the more striking discoveries of the 20th century was that the native and denatured states in many proteins were interconvertible, that by careful control of solution conditions (by for example, dialyzing away a denaturing chemical), a denatured protein could be converted to native form. The issue of how proteins arrive at their native state is an important area of biochemical study, called the study of protein folding.

Through genetic engineering, researchers can alter the sequence and hence the structure, "targeting", susceptibility to regulation and other properties of a protein. The genetic sequences of different proteins may be spliced together to create "chimeric" proteins that possess properties of both. This form of tinkering represents one of the chief tools of cell and molecular biologists to change and to probe the workings of cells. Another area of protein research attempts to engineer proteins with entirely new properties or functions, a field known as protein engineering.

Protein-protein interactions can be screened for using two-hybrid screening.

Protein regulation

Various molecules and ions are able to bind to specific sites on proteins. These sites are called binding sites. They exhibit chemical specificity. The particle that binds is called a ligand. The strength of ligand-protein binding is a property of the binding site known as affinity.

Since proteins are involved in practically every function performed by a cell, the mechanisms for controlling these functions therefore depend on controlling protein activity. Regulation can involve a protein's shape or concentration. Some forms of regulation include:

• Allosteric modulation: When the binding of a ligand at one site on a protein affects the binding of ligand at another site.
• Covalent modulation: When the covalent modification of a protein affects the binding of a ligand or some other aspect of the protein's function.

Diversity

Proteins are generally large molecules, having molecular masses of up to 3,000,000 (the muscle protein titin has a single amino acid chain 27,000 subunits long) however protein masses are generally measured in kiloDaltons (kDa). Such long chains of amino acids are almost universally referred to as proteins, but shorter strings of amino acids are referred to as "polypeptides," "peptides" or rarely, "oligopeptides". The dividing line is undefined, though "polypeptide" usually refers to an amino acid chain lacking tertiary structure which may be more likely to act as a hormone (like insulin), rather than as an enzyme (which depends on its defined tertiary structure for functionality).

Proteins are generally classified as soluble, filamentous or membrane-associated (see integral membrane protein). Nearly all the biological catalysts known as enzymes are soluble proteins (with a recent notable execption being the discovery of ribozymes, RNA molecules with the catalytic properties of enzymes.) Antibodies, the basis of the adaptive immune system, are another example of soluble proteins. Membrane-associated proteins include exchangers and ion channels, which move their substrates from place to place but do not change them; receptors, which do not modify their substrates but may simply shift shape upon binding them. Filamentous proteins make up the cytoskeleton of cells and much of the structure of animals: examples include tubulin, actin, collagen and keratin, all of which are important components of skin, hair, and cartilage. Another special class of proteins consists of motor proteins such as myosin, kinesin, and dynein. These proteins are "molecular motors," generating physical force which can move organelles, cells, and entire muscles.

Molecular surface of several proteins showing their comparative sizes. From left to right are: Antibody (IgG), Hemoglobin, Insulin (a hormone), Adenylate Kinase (an enzyme), and Glutamine Synthetase (an enzyme).

Role of Protein

Functions

Proteins are involved in practically every function performed by a cell, including regulation of cellular functions such as signal transduction and metabolism. For example, protein catabolism requires enzymes termed proteases and other enzymes such as glycosidases.

Within Nutrition

Proteins are separated into two groups: Complete and Incomplete. Incomplete proteins are from plants (except soy) and do not contain the correct proportion of the 20 essential amino acids. Complete proteins come from animal sources (soy protein is a complete protein) and include all 20 amino acids. Protein is in almost everything you eat, but whether all the amino acids are in them depends on what the substance is.

As most vegetarians know, a complete protein may be formed by combining two plant proteins which complement each other. for example, cereals are deficient in lysine, while legumes are deficient in methionine. Eating a combination of beans and rice will satisfy the DRI for protein.

Protein is an important macronutrient to the human diet, supplying the body's needs for nitrogen and amino acids, the building blocks of proteins. The exact amount of dietary protein needed to satisfy these requirements may vary widely depending on age, sex, level of physical activity, and medical condition, as well as the RDA specified by the state.

The recommended intake of protein differs from country to country, but it is marginalised between 0.8 and 1.2g / kg b.w (Per kilogram of bodyweight), however , in more serious athletes, requiring strength, the figure is somewhat between 1.0 and 2.5g per kilogram of Body weight, which is referred to as the maximum protein intake:benefits ratio. ^[1] Although proteins are found in all foods, be it only in small amounts ^[2], protein is still well concentrated in foods such as legumes, nuts, and dairy products, the majority of which are protein choices for vegetarians.

Protein is the major component in the regulation, growth and differentation of muscles, tendons, enzymes, skin, hair, eyes, as well as a tremendous variety of other organs and processes. The quality of protein intake is particularly important because different proteins supply essential amino acids in different proportions. Given an adequate intake of nitrogen, the human body can manufacture 10 of the 20 amino acids from glucose. The remaining 10 amino acids (threonine, valine, tryptophan, isoleucine, leucine, lysine, phenylalanine, and methionine) cannot be manufactured by the body and must be acquired through supplementation. Thus, they are termed essential amino acids.

For use within the body, the majority of protein taken from food consumed is converted by protein catabolism into ammonia which, due to its toxicity, must be converted to either urea or uric acid,or in some animals is excreted in urine. Proteins possessing equal proportions of all essential amino acids in relatively abundant quantities are often termed "complete", or "High-Quality" Proteins, which are generally obtained from animal proteins, such as meat ^[3], and are rated using PDCAAS (Protein Digestibility Corrected Amino Acid Score).

Despite what the name suggests, quality proteins are not essential for good supplementation or nutrition within the average person, however, the difference between amino acids in plant and animal proteins is discernable, particularly for athletes or bodybuilders as plant proteins lack two major amino acids found in animal proteins; lysine within grains, and methionine within legumes, major benefactors to a major athlete's dietary regime. Neverthelss, in terms of quality, amino acids found in plant and animal extracts are identical. ^[4]

Protein deficiency can lead to symptoms such as fatigue, insulin resistance, hair loss, loss of hair pigment, loss of muscle mass , low body temperature, hormonal irregularities, as well as loss of skin elsaticity ^[5]. Severe protein deficiency, encountered only in times of famine, is fatal, due to the lack of material for the body to facilitate as energy.

It has been known that in some "wild diets", in which people lose mass amounts of weight in a short period of time are attributed to deficiencies in protein, and thus loss in muscle mass, and not fat, which is widely known as a dangerous practice, particularly because of the benefits of muscle mass over fat.

Excessive protein intake has also been linked to several problems;

• overreaction within the immune system
• liver dysfunction due to increased toxic residues
• loss of bone density, frailty of bones due to increased acidity in the blood and foundering (foot problems) in horses.

It is assumed by reasearchers on the field, that excessive intake of protein forced increased calcium excretion. If there is to be excessive intake of protein, it is thought that a regular intake of calcium would be able to stablilise, or even increase the uptake of calcium by the small intestine, which would be more beneficial in older women ^[6].

Proteins are often progenitors in allergies and allergic reactions to certain foods. This is because the structure of each form of protein is slightly different; some may trigger a response from the immune system while others remain perfectly safe. Many people are allergic to casein, the protein in milk; gluten, the protein in wheat and other grains; the particular proteins found in peanuts; or those in shellfish or other seafoods. It is extremely unusual for the same person to adversely react to more than two different types of proteins, due to the diversity between protein or amino acid types.

History

The first mention of the word protein, which means of first rank, were from a letter sent by Jöns Jakob Berzelius to Gerhardus Johannes Mulder on 10. July 1838, where he wrote:

«Le nom protéine que je vous propose pour l’oxyde organique de la fibrine et de l’albumine, je voulais le dériver de πρωτειοξ, parce qu’il paraît être la substance primitive ou principale de la nutrition animale.»

Translated as:

"The name protein that I propose for the organic oxide of fibrin and albumin, I wanted to derive from [the Greek word] πρωτειοξ, because it appears to be the primitive or principal substance of animal nutrition."

Investigation of proteins and their properties had been going on since about 1800 when scientists were finding the first signs of this, at the time, unknown class of organic compounds.

See also

• Biochemistry
• Crystallography
• Denatured protein
• Intein
• List of proteins
• Peptide
• Prion
• Proteinoid
• Protein structure prediction
• Protein targeting
• Proteome
• Ribosome
• Standard curve
• Structural genomics

References

1. ^  Kerstetter, J. E., O'Brien, K. O., Insogna, K. L. (2003) "Dietary protein, calcium metabolism, and skeletal homeostasis revisited" . J Clin Endocrinol Metab Vol 78, p584S-592S.
2. ^  Kerstetter, J. E., O'Brien, K. O., Caseria, D.M, Wall, D. E. & Insogna, K. L (2005) "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women" . J Clin Endocrinol Metab (2005) Vol 90, p26-31, Entrez PubMed 15546911.
3. ^  Devine, A., Dick, I. M,, Islam I. M., Dhaliwal, S. S. & Prince, R. L. (2005) "Protein consumption is an important predictor of lower limb bone mass in elderly women" . Am J Clin Nutr (2005) volume 81 pages 423-428, Entrez PubMed 15941897.
4. ^  Jeukendrup, A. & Gleeson, M. (2004) Sport Nutrition - An Introduction to Energy Production and Performance USA : Human Kinetics
5. ^  Bean, A. (2004) Sport Nutrition for Serious Athletes London : Routledge

External links

• The Protein Databank
• UniProt the Universal Protein Resource
• Human Protein Atlas
• iHOP - Information Hyperlinked over Proteins
• Proteins: Biogenesis to Degradation - The Virtual Library of Biochemistry and Cell Biology
• Protein Bioinformatic Tools
• MIT's Laboratory for Protein Molecular Self-Assembly
• Numerous publications on synthetic biomimetic protein-based biomaterials
• Protein Research: Western Blot Protocols, Troubleshooting and Theory
• Amino acid metabolism
• Protein Images

Ribbon diagram of the catalytically perfect enzyme TIM.

An enzyme is a protein that catalyzes, or speeds up, a chemical reaction. The word comes from the Greek ένζυμο, énsymo, which comes from én ("at" or "in") and simo ("leaven" or "yeast"). Certain RNAs also have catalytic activity, but to differentiate them from protein enzymes, they are referred to as RNA enzymes or ribozymes.

Enzymes are essential to sustain life because most chemical reactions in biological cells 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 catalyses 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.

Like all catalysts, enzymes work by lowering the 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, like all catalysts, do not affect the relative energy between the products and reagents, they do not affect equilibrium of a reaction. However, the advantage of enzymes compared to most other catalysts is their sterio-, regio- and chemoselectivity and specificity.

Enzyme activity can be affected by other molecules. Inhibitors are naturally occuring 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 COX-1 and 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.

While all enzymes have a biological role, some enzymes are used commerically for other purposes. Many household cleaners use enzymes to speed up chemical reactions ( i.e., breaking down protein or starch stains in clothes).

More than 5,000 enzymes are known. Typically the suffix -ase is added to the name of the 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 numbers 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 similiar enzymes in the same species may have identical EC numbers.

Etymology and history

Eduard Buchner

The word enzyme comes from Greek: "in leaven". 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 "ferments" in the yeast, which were thought to function only in the presence of living organisms.

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.

3D-Structure

In enzymes, as with other proteins, function is determined by structure. An enzyme can be:

• A monomeric protein, i.e., containing only one polypeptide chain, typically one hundred or more amino acids; or
• an oligomeric protein consisting of several polypeptide chains, different or identical, that act together as a unit.

As with any protein, each monomer is actually produced as a long, linear chain of amino acids, which folds in a particular fashion to produce a three-dimensional product. Individual monomers may then combine via non-covalent interactions to form a multimeric protein.

Cartoon showing the active site of an enzyme.

Most enzymes are larger than the substrates they act on and that only a very small portion of the enzyme, around 10 amino acids, come into direct contact with the substrate(s). This region, where binding of the substrate(s) and then the reaction occurs, is known as the active site of the enzyme. Some enzymes contain sites that bind cofactors, which are needed for catalysis. Certain enzymes 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 (depending on the molecule and enzyme), providing a means for feedback regulation.

Specificity

Enzymes are usually specific as to the reactions they catalyze and the substrates that are involved in these reactions. Shape, charge complementarity, and hydrophillic/hydrophobic character of enzyme and substrate are responsible for this specificity.

"Lock and key" model

Enzymes are very specific and it was suggested by Emil Fischer in 1890 that this was because the enzyme had a particular shape into which the substrate(s) fit exactly. This is often referred to as "the lock and key" model. An enzyme combines with its substrate(s) to form a short-lived enzyme-substrate complex.

Schmatic of Fischer's lock and key model (top) and Koshland's induced fit model (bottom).

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 could be modified as the substrate interacts with the enzyme. The amino acids sidechains which 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.

Modifications

Many enzymes contain not only a protein part but need additionally various modifications. These modifications are made posttranslational, i.e., after the polypeptide chain is synthesized. Additional groups can be synthesized onto the polypeptide chain, e.g., phosphorylation or glycosylation of the enzyme.

Another kind of posttranslational modification is the cleavage and splicing 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 prevents the enzyme from harmful digestion of the pancreas or other tissue. This type of inactive precursor to an enzyme is known as a zymogen.

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 clusters) or organic compounds, which are also known as coenzymes.

Enzymes that require a cofactor, but do not have one bound are called apoenzymes. 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).

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 electrons, atoms, or functional groups from an enzyme to a substrate. Common examples are NAD and NADP, which are involved in electron transfer and coenzyme A, which is involved in the transfer of acetyl groups.

Allosteric modulation

Allosteric enzymes change their stucture in response to binding of effectors. Modulation can be direct, where effectors bind directly to binding sites in the enzyme, or indirect, where the effector binds to other proteins or protein subunits that interact with the allosteric enzyme and thus influence catalytic activity.

Thermodynamics

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 reacts to form the end product. The enzyme stabilizes the transition state, reducing the energy of the transition state and thus the energy required to get over this barrier.

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 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. Carbonic anhydrase catalyzes its reaction in either direction depending on the conditions.

(in tissues - high CO₂ concentration)

(in lungs - low CO₂ concentration)

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 futher 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_max) of the enzyme. In this state, all enzyme active sites are saturated with substrate. However, V_max 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_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.

The efficiency of an enzyme can be expressed in terms of k_cat/K_m. The quantity k_cat, also called the turnover number, incorporates the rate constants for all steps in the reaction, and is the quotient of V_max and the total enzyme concentration. k_cat/K_m 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_cat/K_m, called 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 k_cat/K_m value 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.

The quantum-mechanical (physical) model of enzyme catalysis explains how certain enzymes work faster than previously thought possible. This is achieved by a process known as tunneling, which allows electron and proton transfers to "tunnel" through activation barriers rather go over them.

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, thus substrate and inhibitor compete for the enzyme.

Diagram showing the mechanism of non-competitive inhibition.

Enzymes reaction rates can be decreased by competitive, non-competitive, partially competitive, uncompetitive inhibition, and mixed inhibition.

Competitive inhibition

In competitive inhibition, the inhibitor binds to the substrate binding site as shown (right part b), thus preventing substrate binding. Malonate is a competitive inhibitor of the enzyme succinate dehydrogenase, which catalyzes the oxidation of succinate to fumarate.

Competive inhibition causes the K_m value to increase, but does not effect V_max.

Non-competitive inhibition

Non-competitive inhibitors never bind to the active center, 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 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.

Non-Competive inhibition causes a decrease in V_max, but does not change the K_m value.

Partially competitive inhibition

The mechanism of partially competitive is similar to that of non-competitive inhibition, except that the EIS-complex has catalytic activity, which may be lower or even higher (partially competitive activation) than that of the enzyme-substrate (ES) complex.

Typically has a lower V_max, but an unaffected K_m value.

Uncompetitive inhibition

Uncompetitive inhibition occurs when the inhibitor binds only to the enzyme-substrate complex, not to the free enzyme, the EIS complex is catalytically inactive. This mode of inhibition is rare.

Uncompetive causes a decrease in V_max and the K_m value.

Mixed inhibition

Mixed inhibitors can bind to both the enzyme and the ES complex. It has the properties of both competitive and uncompetive inhibition.

Both a decrease in V_max and an increase in the the K_m value are seen in mixed inhibition.

Metabolic pathways and allosteric enzymes

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. 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 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.

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. 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 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.

The International Union of Biochemistry and Molecular Biology has developed a nomenclature for enzymes, the EC numbers; each enzyme is described by a sequence of four numbers, preceded by "EC". The first number broadly classifies the enzyme based on its mechanism:

The toplevel 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

Application	Enzymes used	Uses	Notes and examples
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.
	Amylase enzymes	Detergents for machine dishwashing to remove resistant starch residues
Baking industry	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	alpha-amylase catalyzes the release sugar monomers from starch
	Protease enzymes	Biscuit manufacturers use them to lower the protein level of flour.
Baby foods	Trypsin	To predigest baby foods
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.	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.
	Amyloglucosidase	Low-calorie beer
	Proteases	Remove cloudiness during storage of beers.
Fruit juices	Cellulases, pectinases	Clarify fruit juices
Dairy industry	Rennin, derived from the stomachs of young ruminant animals (calves, lambs, kids)	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	Roquefort cheese
	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