Enzymes are proteins that
catalyzeCatalysis is the process in which the rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. The catalyst may participate...
(
i.e.,
increase the ratesThe reaction rate or rate of reaction for a reactant or product in a particular reaction is intuitively defined as how fast a reaction takes place...
of)
chemical reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. They are studied by chemists under a field of science called chemistry. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, often coming about...
s. In enzymatic reactions, the
moleculeA molecule is defined as an electrically neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds. Molecules are distinguished from polyatomic ions in this strict sense...
s at the beginning of the process are called
substratesIn biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
, and the enzyme converts them into different molecules, called the
productsIn biochemistry, a product is something "manufactured" by an enzyme from its substrate. For example the products of Lactase are Galactose and Glucose, which are produced from the substrate Lactose.....
. Almost all processes in a
biological cellThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
need enzymes to occur at significant rates. Since enzymes are 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 pathway-Cellular respiration:Several distinct but linked metabolic pathways are used by cells to transfer the energy released by breakdown of fuel molecules to ATP...
s occur in that cell.
Like all catalysts, enzymes work by lowering the
activation energyIn chemistry, activation energy is a term introduced in 1889 by the Swedish scientist Svante Arrhenius, that is defined as the energy that must be overcome in order for a chemical reaction to occur. Arrhenius' research was a follow up of the theories of reaction rate by Serbian physicist Nebojsa...
(
Ea or Δ
G‡) for a reaction, thus dramatically increasing the rate of the reaction. Most enzyme reaction rates are millions of times faster than those of comparable un-catalyzed reactions. As with all catalysts, enzymes are not consumed by the reactions they catalyze, nor do they alter the
equilibriumIn a chemical process, chemical equilibrium is the state in which the chemical activities or concentrations of the reactants and products have no net change over time. Usually, this would be the state that results when the forward chemical process proceeds at the same rate as their reverse reaction...
of these reactions. However, enzymes do differ from most other catalysts by being much more specific. Enzymes are known to catalyze about 4,000 biochemical reactions. A few
RNARibonucleic acid is a biologically important type of molecule that consists of a long chain of nucleotide units. Each nucleotide consists of a nitrogenous base, a ribose sugar, and a phosphate...
molecules called
ribozymeA ribozyme is an RNA molecule that catalyzes a chemical reaction...
s also catalyze reactions, with an important example being some parts of the
ribosomeRibosomes are complexes of RNA and protein that are found in all cells. The ribosome is part of the mechanism that translates the DNA sequence into the protein sequence. Ribosomes from bacteria, archaea and eukaryotes , have significantly different structure and RNA...
. Synthetic molecules called
artificial enzymeAn artificial enzyme is a synthetic, organic molecule prepared to recreate the active site of an enzyme.Enzyme catalysis of chemical reactions occur with high selectivity and rate in a small part of the enzyme macromolecule known as the active site. There, the binding of a substrate close to...
s also display enzyme-like catalysis.
Enzyme activity can be affected by other molecules.
InhibitorsEnzyme inhibitors are molecules that bind to enzymes and decrease their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
are molecules that decrease enzyme activity;
activatorsEnzyme activators are molecules that bind to enzymes and increase their activity. These molecules are often involved in the allosteric regulation of enzymes in the control of metabolism. An example of an enzyme activator working in this way is fructose 2,6-bisphosphate, which activates...
are molecules that increase activity. Many
drugA drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s and
poisonIn the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism...
s are enzyme inhibitors. Activity is also affected by
temperatureIn physics, temperature is a physical property of a system that underlies the common notions of hot and cold; something that feels hotter generally has the higher temperature. Temperature is one of the principal parameters of thermodynamics...
, chemical environment (
e.g.,
pHpH is a measure of the acidity or basicity of a solution. It is defined as the cologarithm of the activity of dissolved hydrogen ions . Hydrogen ion activity coefficients cannot be measured experimentally, so they are based on theoretical calculations...
), and the
concentrationIn chemistry, concentration is the measure of how much of a given substance there is mixed with another substance. This can apply to any sort of chemical mixture, but most frequently the concept is limited to homogeneous solutions, where it refers to the amount of solute in the solvent.To...
of substrate. Some enzymes are used commercially, for example, in the synthesis of
antibioticIn common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria...
s. In addition, some household products use enzymes to speed up biochemical reactions (
e.g., enzymes in biological washing powders break down protein or
fatFats consist of a wide group of compounds that are generally soluble in organic solvents and largely insoluble in water. Chemically, fats are generally triesters of glycerol and fatty acids. Fats may be either solid or liquid at normal room temperature, depending on their structure and composition...
stains on clothes; enzymes in
meat tenderizerA meat tenderizer refers to either a kitchen utensil or a chemical used for tenderizing meat. Enzymes are used as chemical meat tenderizers.The tool is also known as a meat mallet, and is a product used for tenderizing slabs of meat in preparation for cooking the meat...
s break down proteins, making the meat easier to chew).
Etymology and history
As early as the late 1700s and early 1800s, the digestion of
meatMeat is animal flesh that is used as food. Most often, this means the skeletal muscle and associated fat, but it may also describe other edible tissues such as organs, livers, skin, brains, bone marrow, kidneys, or lungs...
by stomach secretions and the conversion of
starchStarch or amylum is a polysaccharide carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds.Starch is produced by all green plants as an energy store and is a major food source for humans....
to
sugarSugar is a class of edible crystalline substances, mainly sucrose, lactose, and fructose. Human taste buds interpret its flavor as sweet. Sugar as a basic food carbohydrate primarily comes from sugar cane and from sugar beet, but also appears in fruit, honey, sorghum, sugar maple , and in many...
s by plant extracts and
salivaSaliva is the watery and usually frothy substance produced in the mouths of humans and most other animals. Saliva is produced in and secreted from the salivary glands...
were known. However, the mechanism by which this occurred had not been identified.
In the 19th century, when studying the
fermentationFermentation in food processing typically is the conversion of carbohydrates to alcohols and carbon dioxide or organic acids using yeasts, bacteria, or a combination thereof, under anaerobic conditions. A more restricted definition of fermentation is the chemical conversion of sugars into ethanol...
of sugar to
alcoholIn chemistry, an alcohol is any organic compound in which a hydroxyl group is bound to a carbon atom of an alkyl or substituted alkyl group. An important group of acohols is formed by the simple acyclic alcohols, the general formula for which is C
nH
2n+1OH...
by
yeastYeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with about 1,500 species currently described; they dominate fungal diversity in the oceans. Most reproduce asexually by budding, although a few do so by binary fission...
,
Louis PasteurLouis Pasteur was a French chemist and microbiologist born in Dole. He is best known for his remarkable breakthroughs in the causes and preventions of disease. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies. His experiments supported the germ...
came to the conclusion that this fermentation was catalyzed by a vital force contained within the yeast cells called "
fermentsVitalism, as defined by the Merriam-Webster dictionary, is#a doctrine that the functions of a living organism are due to a vital principle distinct from biochemical reactions...
", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells."
In 1878, German physiologist
Wilhelm KühneWilhelm Friedrich Kühne was a German physiologist. Born in Hamburg, he is best known today for coining the word enzyme....
(1837–1900) first used the term
enzyme, which comes from
GreekGreek , an independent branch of the Indo-European family of languages, is the language of the Greeks. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. In its ancient form, it is the language of classical...
ενζυμον, "in leaven", to describe this process. The word
enzyme was used later to refer to nonliving substances such as
pepsinPepsin is an enzyme that is released by the chief cells in the stomach and that degrades food proteins into peptides. Pepsin was discovered in 1836 by Theodor Schwann who also coined this enzyme's name from the Greek word pepsis, meaning digestion...
, and the word
ferment was used to refer to chemical activity produced by living organisms.
In 1897,
Eduard BuchnerEduard Buchner was a German chemist and zymologist, the winner of the 1907 Nobel Prize in Chemistry for his work on fermentation.-Early years:...
began to study the ability of yeast extracts that lacked any living yeast cells to ferment sugar. In a series of experiments at the
University of BerlinThe Humboldt University of Berlin is Berlin's oldest university, founded in 1810 as the University of Berlin by the liberal Prussian educational reformer and linguist Wilhelm von Humboldt, whose university model has strongly influenced other European and Western universities...
, he found that the sugar was fermented even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose "
zymaseZymase is an enzyme complex that catalyzes the fermentation of sugar into ethanol and carbon dioxide. As the conversion takes place, the reaction will gradually slow down. They occur naturally in yeasts...
". In 1907, he received the
Nobel Prize in ChemistryThe Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
"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
substrateIn biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
(
e.g.,
lactaseLactase , a part of the β-galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers...
is the enzyme that cleaves
lactoseLactose is a sugar that is found most notably in milk. Lactose makes up around 2–8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey...
) or the type of reaction (
e.g.,
DNA polymeraseA DNA polymerase is an enzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best-known for their role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand...
forms DNA polymers).
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 WillstätterRichard Martin Willstätter was a German organic chemist whose study of the structure of plant pigments, chlorophyll included, won him the 1915 Nobel Prize for Chemistry. Willstätter invented paper chromatography independently of Mikhail Tsvet.-Biography:Willstätter was born in to a Jewish family...
) argued that proteins were merely carriers for the true enzymes and that proteins
per se were incapable of catalysis. However, in 1926,
James B. SumnerJames Batcheller Sumner was an American chemist. He shared the Nobel Prize in Chemistry in 1946 with John Howard Northrop and Wendell Meredith Stanley.-Biography:...
showed that the enzyme
ureaseUrease is an enzyme that catalyzes the hydrolysis of urea into carbon dioxide and ammonia. The reaction occurs as follows:In 1926 James Sumner showed that urease is a protein...
was a pure protein and crystallized it; Sumner did likewise for the enzyme
catalaseCatalase is a common enzyme found in nearly all living organisms which are exposed to oxygen, where it functions to catalyze the decomposition of hydrogen peroxide to water and oxygen...
in 1937. The conclusion that pure proteins can be enzymes was definitively proved by
NorthropJohn Howard Northrop was an American biochemist who won, with James Batcheller Sumner and Wendell Meredith Stanley, the 1946 Nobel Prize in Chemistry...
and
StanleyWendell Meredith Stanley was an American biochemist, virologist and Nobel laureate.-Biography:Stanley was born in Ridgeville, Indiana, and earned a BS in Chemistry at Earlham College in Richmond, Indiana. He then studied at the University of Illinois, gaining an MS in science in 1927 followed by...
, who worked on the digestive enzymes pepsin (1930), trypsin and chymotrypsin. These three scientists were awarded the 1946 Nobel Prize in Chemistry.
This discovery that enzymes could be crystallized eventually allowed their structures to be solved by
x-ray crystallographyX-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and diffracts into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a three-dimensional picture...
. This was first done for
lysozymeLysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, are a family of enzymes which damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine...
, an enzyme found in tears, saliva and
egg whiteEgg white is the common name for the clear liquid contained within an egg. It is the cytoplasm of the egg, which until fertilization is a single cell . It consists mainly of about 15% proteins dissolved in water...
s that digests the coating of some bacteria; the structure was solved by a group led by
David Chilton PhillipsDavid Chilton Phillips, Baron Phillips of Ellesmere, KBE, FRS is considered to be a founding father of the now expanding field of structural biology and was an influential figure in science and government...
and published in 1965. This high-resolution structure of lysozyme marked the beginning of the field of
structural biologyStructural biology is a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations in their structures affect their function...
and the effort to understand how enzymes work at an atomic level of detail.
Structures and mechanisms
Enzymes are generally
globular proteinGlobular proteins, or spheroproteins are one of the three main protein classes, comprising "globe"-like proteins that are more or less soluble in aqueous solutions...
s and range from just 62 amino acid residues in size, for the
monomerA monomer is a small molecule that may become chemically bonded to other monomers to form a polymer...
of
4-oxalocrotonate tautomerase4-Oxalocrotonate tautomerase is an enzyme that converts 2-hydroxymuconate to the αβ-unsaturated ketone, 2-oxo-3-hexenedioate. This enzyme forms part of a bacterial metabolic pathway that oxidatively catabolizes toluene, o-xylene, 3-ethyltoluene, and 1,2,4-trimethylbenzene into intermediates of the...
, to over 2,500 residues in the animal
fatty acid synthaseFatty acid synthase is enzymatic system composed of 272 kDa multifunctional polypeptide, in which substrates are handed from one functional domain to the next.-Metabolic function:...
. A small number of RNA-based biological catalysts exist, with the most common being the
ribosomeRibosomes are complexes of RNA and protein that are found in all cells. The ribosome is part of the mechanism that translates the DNA sequence into the protein sequence. Ribosomes from bacteria, archaea and eukaryotes , have significantly different structure and RNA...
; these are referred to as either RNA-enzymes or
ribozymeA ribozyme is an RNA molecule that catalyzes a chemical reaction...
s. The activities of enzymes are determined by their
three-dimensional structureIn biochemistry, quaternary structure is the arrangement of multiple folded protein molecules in a multi-subunit complex.-Description and examples:...
. 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.
Most enzymes are much larger than the substrates they act on, and only a small portion of the enzyme (around 3–4
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and one of the twenty R-groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H
2NCHRCOOH, where R is an organic substituent...
s) 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 siteThe active site of an enzyme contains the catalytic and binding sites. The structure and chemical properties of the active site allow the recognition and binding of the substrate....
. Enzymes can also contain sites that bind
cofactorsA cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes and cofactors can be considered "helper molecules/ions" that assist in biochemical transformations...
, 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
feedbackFeedback describes the situation when output from an event or phenomenon in the past will influence the same event/phenomenon in the present or future....
regulation.
Like all proteins, enzymes are made as long, linear chains of amino acids that
foldProtein folding is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
to produce a
three-dimensional productIn biochemistry and chemistry, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
. Each unique amino acid sequence produces a specific structure, which has unique properties. Individual protein chains may sometimes group together to form a
protein complexA multiprotein complex is a group of two or more proteins. Protein complexes are a form of quaternary structure. Proteins in a protein complex are linked by non-covalent protein-protein interactions, and different protein complexes have different degrees of stability over time...
. Most enzymes can be
denaturedDenaturation is a process in which proteins or nucleic acids lose their tertiary and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat. If proteins in a living cell are denatured, this...
—that is, unfolded and inactivated—by heating or chemical denaturants, which disrupt the
three-dimensional structureIn biochemistry and chemistry, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
of the protein. Depending on the enzyme, denaturation may be reversible or irreversible.
Specificity
Enzymes are usually very specific as to which reactions they catalyze and the
substratesIn biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
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
stereospecificityIn chemistry, stereospecificity is the property of a reaction mechanism that leads to different stereoisomeric reaction products from different stereoisomeric reactants, or which operates on only one of the stereoisomers....
,
regioselectivityIn chemistry, regioselectivity is the preference of one direction of chemical bond making or breaking over all other possible directions . It can often apply to which of many possible positions a reagent will affect, such as which proton a strong base will abstract from an organic molecule, or...
and
chemoselectivityChemical reactions are defined usually in small contexts , such generalizations are a matter of utility...
.
Some of the enzymes showing the highest specificity and accuracy are involved in the copying and
expressionGene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as rRNA genes or tRNA genes, the product is a functional RNA...
of the
genomeIn modern molecular biology the genome refers to all of its hereditary information encoded in DNA .The genome includes both the genes and the non-coding sequences of the DNA. The term was adapted in 1920 by Hans Winkler, Professor of Botany at the University of Hamburg, Germany...
. These enzymes have "proof-reading" mechanisms. Here, an enzyme such as
DNA polymeraseA DNA polymerase is an enzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best-known for their role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand...
catalyzes a reaction in a first step and then checks that the product is correct in a second step. This two-step process results in average error rates of less than 1 error in 100 million reactions in high-fidelity
mammalMammals are a class of vertebrate animals whose females are characterized by the possession of mammary glands while both males and females are characterized by sweat glands, hair, three middle ear bones used in hearing, and a neocortex region in the brain.Mammals are divided into three main...
ian polymerases. Similar proofreading mechanisms are also found in
RNA polymeraseRNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
,
aminoacyl tRNA synthetaseAn aminoacyl tRNA synthetase is an enzyme that catalyzes the esterification of a specific amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA.-Mechanism:...
s and
ribosomeRibosomes are complexes of RNA and protein that are found in all cells. The ribosome is part of the mechanism that translates the DNA sequence into the protein sequence. Ribosomes from bacteria, archaea and eukaryotes , have significantly different structure and RNA...
s.
Some enzymes that produce
secondary metaboliteSecondary metabolites are organic compounds that are not directly involved in the normal growth, development, or reproduction of organisms. Unlike primary metabolites, absence of secondary metabolities does not result in immediate death, but rather in long-term impairment of the organism's...
s are described as promiscuous, as they can act on a relatively broad range of different substrates. It has been suggested that this broad substrate specificity is important for the evolution of new biosynthetic pathways.
"Lock and key" model
Enzymes are very specific, and it was suggested by
Emil FischerHermann Emil Fischer was a German chemist and recipient of the Nobel Prize for Chemistry in 1902.-Early years:...
in 1894 that this was because both the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another. This is often referred to as "the lock and key" model. However, while this model explains enzyme specificity, it fails to explain the stabilization of the transition state that enzymes achieve.
The "lock and key" model has proven inaccurate, and the induced fit model is the most currently accepted enzyme-substrate-coenzyme figure.
Induced fit model
In 1958,
Daniel KoshlandDaniel Edward Koshland, Jr. reorganized the study of biology at the University of California at Berkeley and was the editor of the leading US science journal, Science, during the decade 1985-1995...
suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continually reshaped by interactions with the substrate as the substrate interacts with the enzyme. As a result, the substrate does not simply bind to a rigid active site; the amino acid side chains which make up the active site are molded into the precise positions that enable the enzyme to perform its catalytic function. In some cases, such as glycosidases, the substrate molecule also changes shape slightly as it enters the active site. The active site continues to change until the substrate is completely bound, at which point the final shape and charge is determined.
Mechanisms
Enzymes can act in several ways, all of which lower ΔG
‡:
- Lowering the activation energy
In chemistry, activation energy is a term introduced in 1889 by the Swedish scientist Svante Arrhenius, that is defined as the energy that must be overcome in order for a chemical reaction to occur. Arrhenius' research was a follow up of the theories of reaction rate by Serbian physicist Nebojsa...
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 only when the temperature comes back to normal does the enzyme regain its shape. Some enzymes like thermolabile enzymes work best at low temperatures.
Interestingly, this entropic effect involves destabilization of the ground state, and its contribution to catalysis is relatively small.
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. Apparently, the most effective way for reaching large stabilization is the use of electrostatic effects, in particular, by having a relatively fixed polar environment that is oriented toward the charge distribution of the transition state. Such an environment does not exist in the uncatalyzed reaction in water.
Dynamics and function
The internal dynamics of enzymes is connected to their mechanism of catalysis.
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 domainA protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
. 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. 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. These new insights also have implications in understanding allosteric effects and developing new drugs.
Allosteric modulation
Allosteric enzymes change their structure in response to binding of
effectorsAn effector is a molecule that binds to a protein and thereby alters the activity of that protein. A modulator molecule binds to a regulatory site during allosteric modulation and allosterically modulates the shape of the protein.- Types of effectors :* Activators* Inhibitors....
. Modulation can be direct, where the effector binds directly to
binding siteIn biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands, or more specifically, protein ligands—form a chemical bond....
s in the enzyme, or indirect, where the effector binds to other proteins or
protein subunitIn structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally-occurring proteins and enzymes are multimeric...
s that interact with the allosteric enzyme and thus influence catalytic activity.
Cofactors
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. Cofactors can be either inorganic (
e.g.,
metal ionsMetal Ions in Life Sciences is a series of books edited by Astrid, Helmut and Roland Sigel, now published by the Royal Society of Chemistry which reflects the interdisciplinary nature of biological inorganic chemistry. Six volumes have been produced, a seventh volume is in the press and two more...
and
iron-sulfur clusterFor biological Fe-S clusters, see iron-sulfur proteins.Iron-sulfur clusters are ensembles of iron and sulfide centres. Fe-S clusters are most often discussed in the context of the biological role for iron-sulfur proteins. Many Fe-S clusters are known in the area of organometallic chemistry and as...
s) or organic compounds (e.g., flavin and
hemeA heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin...
). 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
NADHNicotinamide adenine dinucleotide, abbreviated NAD
+, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups, with one nucleotide containing an adenine base and the other containing...
,
NADPHNicotinamide adenine dinucleotide phosphate is used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent....
and
adenosine triphosphateAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
. These molecules transfer chemical groups between enzymes.
An example of an enzyme that contains a cofactor is
carbonic anhydraseThe carbonic anhydrases form a family of enzymes that catalyze the rapid conversion of carbon dioxide to bicarbonate and protons, a reaction that occurs rather slowly in the absence of a catalyst...
, and is shown in the
ribbon diagramRibbon diagrams, also known as Richardson Diagrams, are 3D schematic representations of protein structure and are one of the most common methods of protein depiction used today. Ribbon diagrams are generated by interpolating a smooth curve through the polypeptide backbone...
above with a zinc cofactor bound as part of its active site. 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
redoxRedox describes all chemical reactions in which atoms have their oxidation number changed....
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.,
thiamine pyrophosphateThiamine pyrophosphate , or thiamine diphosphate , is a thiamine derivative which is produced by the enzyme thiamine pyrophosphatase. Thiamine pyrophosphate is a coenzyme that is present in all living systems, in which it catalyzes several biochemical reactions...
in the enzyme
pyruvate dehydrogenasePyruvate dehydrogenase complex is a complex of three enzymes that transform pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this complex links the glycolysis metabolic pathway to the...
). The term "holoenzyme" can also be applied to enzymes that contain multiple protein subunits, such as the
DNA polymeraseA DNA polymerase is an enzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best-known for their role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand...
s; here the holoenzyme is the complete complex containing all the subunits needed for activity.
Coenzymes
Coenzymes are small organic molecules that transport chemical groups from one enzyme to another. Some of these chemicals such as
riboflavinRiboflavin , also known as vitamin B
2, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B
2 is required...
,
thiamineThiamine or thiamin, sometimes called aneurin, is a water-soluble vitamin of the B complex , whose phosphate derivatives are involved in many cellular processes. The best characterized form is thiamine diphosphate , a coenzyme in the catabolism of sugars and amino acids...
and
folic acidFolic acid and folate , as well as pteroyl-L-glutamic acid and pteroyl-L-glutamate, are forms of the water-soluble vitamin B
9...
are vitamins (compounds which cannot be synthesized by the body and must be acquired from the diet). The chemical groups carried include the
hydrideHydride is the name given to the negative ion of hydrogen, H−. Practically, the term hydride has two distinct but overlapping meanings. In the chemical vernacular the term hydride refers to a hydrogen atom that formally reacts as a hydrogen anion under common conditions as well as...
ion (H
-) carried by
NAD or NADP+Nicotinamide adenine dinucleotide, abbreviated NAD
+, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups, with one nucleotide containing an adenine base and the other containing...
, the acetyl group carried by
coenzyme ACoenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle...
, formyl, methenyl or methyl groups carried by
folic acidFolic acid and folate , as well as pteroyl-L-glutamic acid and pteroyl-L-glutamate, are forms of the water-soluble vitamin B
9...
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.
Coenzymes are usually regenerated and their concentrations maintained at a steady level inside the cell: for example, NADPH is regenerated through the
pentose phosphate pathwayThe pentose phosphate pathway is a process that generates NADPH and pentoses sugars. There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars...
and
S-adenosylmethionine by methionine adenosyltransferase.
Thermodynamics
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
ATPAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
is often used to drive other 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 anhydraseThe carbonic anhydrases form a family of enzymes that catalyze the rapid conversion of carbon dioxide to bicarbonate and protons, a reaction that occurs rather slowly in the absence of a catalyst...
catalyzes its reaction in either direction depending on the concentration of its reactants.
- (in tissues
Tissue is a cellular organizational level intermediate between cells and a complete organism. Hence, a tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function...
; high CO2 concentration)
- (in lung
The lung or pulmonary system is the essential respiration organ in air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located in the chest on either side of the heart...
s; low CO2 concentration)
Nevertheless, if the equilibrium is greatly displaced in one direction, that is, in a very
exergonicExergonic means to release energy in the form of work. Its etymology stems from the suffix -ergonic, as derived from the Greek root ergon, meaning work, combined with the Greek prefix ex-, meaning out of. By thermodynamic standards, work, a form of energy, is defined as moving from the system to...
reaction, the reaction is
effectively irreversible. Under these conditions the enzyme will, in fact, only catalyze the reaction in the thermodynamically allowed direction.
Kinetics
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 assayEnzyme assays are laboratory methods for measuring enzymatic activity. They are vital for the study of enzyme kinetics and enzyme inhibition.-Enzyme units:...
s.
In 1902 Victor Henri proposed a quantitative theory of enzyme kinetics, 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 the German chemist
Leonor MichaelisLeonor Michaelis was a German biochemist and physician famous for his work with Maud Menten in enzyme kinetics and Michaelis-Menten kinetics....
and his Canadian postdoc Maud Leonora Menten repeated Henri's experiments and confirmed his equation which is referred to as Henri-Michaelis-Menten kinetics (sometimes also
Michaelis-Menten kineticsMichaelis–Menten kinetics approximately describes the kinetics of many enzymes. It is named after Leonor Michaelis and Maud Menten. This kinetic model is relevant to situations where very simple kinetics can be assumed, Michaelis–Menten kinetics (occasionally also referred to as...
). Their work was further developed by
G. E. BriggsGeorge Edward Briggs was a British botanist. He was Professor of Botany, Cambridge University. He was elected a Fellow of the Royal Society in 1935.Briggs wrote important papers on Enzymes....
and
J. B. S. HaldaneJohn Burdon Sanderson Haldane FRS , known as Jack , was a British-born geneticist and evolutionary biologist...
, who derived kinetic equations that are still widely used today.
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.
Enzymes can catalyze up to several million reactions per second. For example, the uncatalyzed decarboxylation of
orotidine 5'-monophosphateOrotidine 5'-monophosphate , also known as orotidylic acid, is a pyrimidine nucleotide which is the last intermediate in the biosynthesis of uridine monophosphate....
has a half life of 78 million years. However, when the enzyme
orotidine 5'-phosphate decarboxylaseOrotidine 5'-phosphate decarboxylase is an enzyme involved in pyrimidine metabolism.-Function:The enzyme converts orotidine monophosphate to uridine monophosphate by liberating carbon dioxide. It is known for being an extraordinarily efficient catalyst capable of accelerating the uncatalyzed...
is added, the same process takes just 25 milliseconds. 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. 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 velocity (
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 velocity. Each enzyme has a characteristic
Km for a given substrate, and this can show how tight the binding of the substrate is to the enzyme. Another useful constant is
kcat, 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
kcat/
Km. 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 10
8 to 10
9 (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 perfectA catalytically perfect enzyme or kinetically perfect enzyme is an enzyme that catalyzes so efficiently, that almost every time enzyme meets its substrate, the reaction occurs. kcat/Km factor of such enzyme is of order 108 to 109 M-1...
or
kinetically perfect. Example of such enzymes are
triose-phosphate isomeraseTriose-phosphate isomerase , is an enzyme that catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate....
,
carbonic anhydraseThe carbonic anhydrases form a family of enzymes that catalyze the rapid conversion of carbon dioxide to bicarbonate and protons, a reaction that occurs rather slowly in the absence of a catalyst...
,
acetylcholinesteraseAcetylcholinesterase, also known as AChE, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic synapses in the central nervous system, where its activity serves to terminate synaptic...
,
catalaseCatalase is a common enzyme found in nearly all living organisms which are exposed to oxygen, where it functions to catalyze the decomposition of hydrogen peroxide to water and oxygen...
, fumarase, β-lactamase, and
superoxide dismutaseSuperoxide dismutases are a class of enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen...
.
Michaelis-Menten kinetics relies on the law of mass action, which is derived from the assumptions of free
diffusionMolecular diffusion, often called simply diffusion, is a net transport of molecules from a region of higher concentration to one of lower concentration by random molecular motion. The result of diffusion is a gradual mixing of material...
and thermodynamically driven random collision. However, many biochemical or cellular processes deviate significantly from these conditions, because of
macromolecular crowdingThe phenomenon of macromolecular crowding alters the properties of molecules in a solution when high concentrations of macromolecules such as proteins are present. Such conditions occur routinely in living cells; for instance, the cytosol of Escherichia coli contains about 300-400 milligrammes per...
, phase-separation of the enzyme/substrate/product, or one or two-dimensional molecular movement. In these situations, a
fractalA fractal is "a rough or fragmented geometric shape that can be split into parts, each of which is a reduced-size copy of the whole," a property called self-similarity...
Michaelis-Menten kineticsMichaelis–Menten kinetics approximately describes the kinetics of many enzymes. It is named after Leonor Michaelis and Maud Menten. This kinetic model is relevant to situations where very simple kinetics can be assumed, Michaelis–Menten kinetics (occasionally also referred to as...
may be applied.
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
tryptamineTryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived...
. 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
Enzyme reaction rates can be decreased by various types of
enzyme inhibitorEnzyme inhibitors are molecules that bind to enzymes and decrease their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
s.
Competitive inhibition
In competitive inhibition, the inhibitor and substrate compete for the enzyme (i.e., they can not bind at the same time). Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example,
methotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug used in treatment of cancer and autoimmune diseases. It acts by inhibiting the metabolism of folic acid...
is a competitive inhibitor of the enzyme
dihydrofolate reductaseDihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry...
, which catalyzes the reduction of
dihydrofolateFolic acid and folate , as well as pteroyl-L-glutamic acid and pteroyl-L-glutamate, are forms of the water-soluble vitamin B
9...
to
tetrahydrofolateFolic acid and folate , as well as pteroyl-L-glutamic acid and pteroyl-L-glutamate, are forms of the water-soluble vitamin B
9...
. The similarity between the structures of folic acid and this drug are shown in the figure to the
right bottom. Note that binding of the inhibitor need
not be to the substrate binding site (as frequently stated), if binding of the inhibitor changes the conformation of the enzyme to prevent substrate binding and
vice versa. In competitive inhibition the maximal velocity of the reaction is not changed, but higher substrate concentrations are required to reach a given velocity, increasing the apparent K
m.
Uncompetitive inhibition
In uncompetitive inhibition the inhibitor can not bind to the free enzyme, but 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 same time as the substrate, i.e. they
never bind 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 V
max changes. But because the substrate can still bind to the enzyme, the K
m stays the same.
Mixed inhibition
This type of inhibition resembles the non-competitive, except that the EIS-complex has residual enzymatic activity.
In many organisms inhibitors may act as part of a
feedbackFeedback describes the situation when output from an event or phenomenon in the past will influence the same event/phenomenon in the present or future....
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 feedbackNegative feedback occurs when the output of a system acts to oppose changes to the input of the system; with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
. Enzymes which 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).
Irreversible inhibitors react with the enzyme and form a
covalentA covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms, or between atoms and other covalent bonds...
adduct with the protein. The inactivation is irreversible. These compounds include
eflornithineEflornithine is a drug manufactured by Sanofi-Aventis that has various uses. It was initially developed for cancer treatment, but, while having little use in treating malignancies, it was found to be highly effective in African trypanosomiasis , especially the West African form...
a drug used to treat the parasitic disease sleeping sickness.
PenicillinPenicillin is a group of antibiotics derived from Penicillium fungi. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections...
and
AspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication....
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. An common example of an inhibitor that is used as a drug is
aspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication....
, which inhibits the
COX-1Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
and
COX-2Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
enzymes that produce the
inflammationInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a...
messenger
prostaglandinA prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
, thus suppressing pain and inflammation. However, other enzyme inhibitors are poisons. For example, the poison
cyanideA cyanide is any chemical compound that contains the cyano group , which consists of a carbon atom triple-bonded to a nitrogen atom. Inorganic cyanides are hydrogen cyanide salts in which cyanide is generally the anion CN
-. Organic compounds that have a -C≡N functional group bonded to...
is an irreversible enzyme inhibitor that combines with the copper and iron in the active site of the enzyme
cytochrome c oxidaseThe enzyme cytochrome c oxidase or Complex IV is a large transmembrane protein complex found in bacteria and the mitochondrion.It is the last enzyme in the respiratory electron transport chain of mitochondria located in the mitochondrial membrane...
and blocks
cellular respirationCellular respiration is one of the key ways a cell gains useful energy. It is the set of the metabolic reactions and processes that take place in organisms' cells to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products...
.
Biological function
Enzymes serve a wide variety of
functionsA function is part of an answer to a question about why some object or process occurred in a system that evolved through a process of selection. Thus, function refers forward from the object or process, along some chain of causation, to the goal or success...
inside living organisms. They are indispensable for
signal transductionIn biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemical reactions inside the cell, which are carried out by enzymes and activated by second messengers,...
and cell regulation, often via
kinaseIn chemistry and biochemistry, a kinase, alternatively known as a phosphotransferase, is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates. The process is referred to as phosphorylation...
s and
phosphataseA phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...
s. They also generate movement, with
myosinMyosins are a large family of motor proteins found in eukaryotic tissues. They are responsible for actin-based motility.Following the discovery by Pollard and Korn of enzymes with myosin-like function in Acanthamoeba castellanii, a large number of divergent myosin genes have been discovered...
hydrolysing ATP to generate
muscle contractionMuscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten or remain the same...
and also moving cargo around the cell as part of the
cytoskeletonThe cytoskeleton is a cellular "scaffolding" or "skeleton" contained within the cytoplasm. The cytoskeleton is present in all cells; it was once thought this structure was unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
. Other ATPases in the cell membrane are
ion pumpsIn biology, an ion transporter, also called an ion pump, is a transmembrane protein that moves ions across a plasma membrane against their concentration gradient, in contrast to ion channels, where ions go through passive transport-Energy source:...
involved in
active transportActive transport is the mediated process of moving particles across a biological membrane against a concentration gradient. If the process uses chemical energy, such as from adenosine triphosphate , it is termed primary active transport. Secondary active transport involves the use of an...
. Enzymes are also involved in more exotic functions, such as
luciferaseLuciferase is a generic term for the class of oxidative enzymes used in bioluminescence and is distinct from a photoprotein. One famous example is the firefly luciferase from the firefly Photinus pyralis. Luciferase is a generic term for the class of oxidative enzymes used in bioluminescence and...
generating light in
firefliesLampyridae is a family of insects in the beetle order Coleoptera. They are winged beetles, and commonly called fireflies or lightning bugs for their conspicuous crepuscular use of bioluminescence to attract mates or prey. Fireflies are capable of producing a "cold light", containing no ultraviolet...
.
VirusA virus is an infectious agent too small to be seen directly with a light microscope. They are not made of cells and can only replicate inside the cells of another organism . Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es can also contain enzymes for infecting cells, such as the HIV integrase and
reverse transcriptaseIn molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse transcribed into a...
, or for viral release from cells, like the
influenzaInfluenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals. The name influenza is Italian and means "influence"...
virus
neuraminidaseNeuraminidase enzymes are glycoside hydrolase enzymes which cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of influenza...
.
An important function of enzymes is in the digestive systems of animals. Enzymes such as amylases and proteases break down large molecules (
starchStarch or amylum is a polysaccharide carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds.Starch is produced by all green plants as an energy store and is a major food source for humans....
or
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s, respectively) into smaller ones, so they can be absorbed by the intestines. Starch molecules, for example, are too large to be absorbed from the intestine, but enzymes hydrolyse the starch chains into smaller molecules such as
maltoseMaltose, or malt sugar, is a disaccharide formed from two units of glucose joined with an α linkage. It is the second member of an important biochemical series of glucose chains...
and eventually
glucoseGlucose , a monosaccharide also known as - grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate...
, which can then be absorbed. Different enzymes digest different food substances. In ruminants which have herbivorous diets, microorganisms in the gut produce another enzyme,
cellulaseCellulase refers to a class of enzymes produced chiefly by fungi, bacteria, and protozoans that catalyze the cellulolysis of cellulose. However, there are also cellulases produced by other types of organisms such as plants and animals. Several different kinds of cellulases are known, which differ...
to break down the cellulose cell walls of plant fiber.
Several enzymes can work together in a specific order, creating
metabolic pathway-Cellular respiration:Several distinct but linked metabolic pathways are used by cells to transfer the energy released by breakdown of fuel molecules to ATP...
s. In a metabolic pathway, one enzyme takes the product of another enzyme as a substrate. After the catalytic reaction, the product is then passed on to another enzyme. Sometimes more than one enzyme can catalyze the same reaction in parallel, this can allow more complex regulation: with for example a low constant activity 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
glycolysisGlycolysis is the metabolic pathway that converts glucose, C
6H
12O
6, into pyruvate, C
3H
6O
3-...
could not exist independently of enzymes. Glucose, for example, can react directly with ATP to become
phosphorylatedPhosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation turns many protein enzymes on and off, causing or preventing the mechanisms of diseases such as cancer and diabetes....
at one or more of its carbons. In the absence of enzymes, this occurs so slowly as to be insignificant. However, if
hexokinaseA hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....
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-phosphateGlucose 6-phosphate is glucose sugar phosphorylated on carbon 6. This compound is very common in cells as the vast majority of glucose entering a cell will become phosphorylated in this way....
is found to be the only significant product. Consequently, the network of metabolic pathways within each cell depends on the set of functional enzymes that are present.
Control of activity
There are five main ways that enzyme activity is controlled in the cell.
- Enzyme production (transcription
Transcription, or RNA synthesis, is the process of creating an equivalent RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA in the presence of the correct enzymes...
and translationTranslation is the first stage of protein biosynthesis . Translation is the production of proteins by decoding mRNA produced in transcription. Translation occurs in the cytoplasm where the ribosomes are located. Ribosomes are made of a small and large subunit which surrounds the mRNA...
of enzyme genes) can be enhanced or diminished by a cell in response to changes in the cell's environment. This form of gene regulationGene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.Regulation of gene expression includes the processes that cells and viruses use to turn the information in genes into gene products...
is called enzyme induction and inhibition (see enzyme induction). For example, bacteria may become resistant to antibioticsAntibiotic resistance is the ability of a microorganism to withstand the effects of antibiotics. It is a specific type of drug resistance. Antibiotic resistance evolves via natural selection acting upon random mutation, but it can also be engineered by applying an evolutionary stress on a population...
such as penicillinPenicillin is a group of antibiotics derived from Penicillium fungi. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections...
because enzymes called beta-lactamaseBeta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephalosporins , cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
s are induced that hydrolyse the crucial beta-lactam ring||-||-||-||-||-||-||}A beta-lactam ring is a lactam with a heteroatomic ring structure, consisting of three carbon atoms and one nitrogen atom...
within the penicillin molecule. Another example are enzymes in the liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
called cytochrome P450 oxidaseCytochrome P450 is a very large and diverse superfamily of hemoproteins found in all domains of life. Cytochromes P450 use a plethora of both exogenous and endogenous compounds as substrates in enzymatic reactions...
s, which are important in drug metabolismDrug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...
. Induction or inhibition of these enzymes can cause drug interactionA drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interaction between drugs come to mind...
s.
- Enzymes can be compartmentalized, with different metabolic pathways occurring in different cellular compartment
Cellular compartments in cell biology comprise all closed parts within a cell whose lumen is usually surrounded by a single or double lipid layer membrane. Most organelles are compartments like mitochondria, chloroplasts , peroxisomes, lysosomes, the endoplasmic reticulum, the cell nucleus or the...
s. For example, fatty acids are synthesized by one set of enzymes in the cytosolThe cytosol or intracellular fluid is the liquid found inside cells. In eukaryotes this liquid is separated by cell membranes from the contents of the organelles suspended in the cytosol, such as the mitochondrial matrix inside the mitochondrion...
, endoplasmic reticulumThe endoplasmic reticulum is an eukaryotic organelle that forms an interconnected network of tubules, vesicles, and cisternae within cells. The lacey membranes of the endoplasmic reticulum were first seen by Keith R. Porter, Albert Claude, and Ernest F...
and the Golgi apparatusThe Golgi apparatus is an organelle found in most eukaryotic cells...
and used by a different set of enzymes as a source of energy in the mitochondrionIn cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5–10 micrometers in diameter...
, through β-oxidation.
- Enzymes can be regulated by inhibitors
Enzyme inhibitors are molecules that bind to enzymes and decrease their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
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 mechanismNegative feedback occurs when the output of a system acts to oppose changes to the input of the system; with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
, 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 allocate materials and energy economically, and prevents the manufacture of excess end products. The control of enzymatic action helps to maintain a stable internal environmentHomeostasis is the property of a system, either open or closed, that regulates its internal environment and tends to maintain a stable, constant condition...
in living organisms.
- Enzymes can be regulated through post-translational modification. This can include phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation turns many protein enzymes on and off, causing or preventing the mechanisms of diseases such as cancer and diabetes....
, myristoylationMyristic acid, also called tetradecanoic acid or 14:0 is a common saturated fatty acid with the molecular formula CH
312COOH. A myristate is a salt or ester of myristic acid....
and glycosylationGlycosylation is the enzymatic process that links saccharides to produce glycans, attached to proteins, lipids, or other organic molecules. This enzymatic process produces one of the fundamental biopolymers found in cells . Glycosylation is a form of co-translational and post-translational...
. For example, in the response to insulinInsulin is a hormone that has extensive effects on metabolism and other body functions, such as vascular compliance. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle, and stopping use of fat as an energy...
, the phosphorylationPhosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation turns many protein enzymes on and off, causing or preventing the mechanisms of diseases such as cancer and diabetes....
of multiple enzymes, including glycogen synthaseGlycogen synthase is a glycosyltransferase enzyme that catalyses the reaction of UDP-glucose and n to yield UDP and n+1.In other words, this enzyme...
, helps control the synthesis or degradation of glycogenGlycogen is the molecule that functions as the secondary long-term energy storage in animal cells. It is made primarily by the liver and the muscles, but can also be made by glycogenesis within the brain and stomach...
and allows the cell to respond to changes in blood sugarBlood sugar concentration, or glucose level, refers to the amount of glucose present in the blood of a human or animal. Normally, in mammals the blood glucose level is maintained at a reference range between about 3.6 and 5.8 mM...
. Another example of post-translational modification is the cleavage of the polypeptide chain. ChymotrypsinChymotrypsin is a digestive enzyme that can perform proteolysis. Chymotrypsin cleaves peptides at the carboxyl side of tyrosine, tryptophan, and phenylalanine because these three amino acids contain aromatic rings, which fit into a 'hydrophobic pocket' in the enzyme...
, a digestive proteaseA protease breaks down proteins. A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein...
, is produced in inactive form as chymotrypsinogenChymotrypsinogen is a precursor of the digestive enzyme chymotrypsin .This molecule is inactive and must be cleaved by trypsin, and then by other...
in the pancreasThe pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as an exocrine gland, secreting pancreatic juice containing digestive enzymes that pass to...
and transported in this form to the stomachIn most mammals, the stomach is a hollow, muscular organ of the gastrointestinal tract , between the esophagus and the small intestine. It is involved in the second phase of digestion, following mastication . The word stomach is derived from the Latin stomachus, which derives from the Greek word...
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 zymogenA zymogen is an inactive enzyme precursor. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it...
.
- Some enzymes may become activated when localized to a different environment (eg. from a reducing (cytoplasm
The cytoplasm is the part of a cell that is enclosed within the cell membrane. In eukaryotic cells, the cytoplasm contains organelles, such as mitochondria, which are filled with liquid that is kept separate from the rest of the cytoplasm by biological membranes. The contents of the cell nucleus...
) to an oxidising (periplasm) environment, high pH to low pH etc). For example, hemagglutininInfluenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein...
in the influenzaInfluenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals. The name influenza is Italian and means "influence"...
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 lysosomethumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s:
[[nucleolus]]
[[cell nucleus|nucleus]]
[[ribosomes]]
[[vesicle |vesicle]]
...
.
Involvement in disease
Since the tight control of enzyme activity is essential for
homeostasisHomeostasis is the property of a system, either open or closed, that regulates its internal environment and tends to maintain a stable, constant condition...
, 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
phenylketonuriaPhenylketonuria is an autosomal recessive genetic disorder characterized by a deficiency in the hepatic enzyme phenylalanine hydroxylase . This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine...
. A mutation of a single amino acid in the enzyme
phenylalanine hydroxylasePhenylalanine hydroxylase is an enzyme which catalyses the reaction responsible for the addition of an hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine:...
, which catalyzes the first step in the degradation of
phenylalaninePhenylalanine is an α-amino acid with the formula HO
2CCHCH
2C
6H
5. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. The codons for
L-phenylalanine are UUU and UUC...
, results in build-up of phenylalanine and related products. This can lead to
mental retardationMental retardation is a generalized disorder, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors with onset before the age of 18...
if the disease is untreated.
Another example is when
germline mutationA germline mutation is any detectable and heritable variation in the lineage of germ cells. Mutations in these cells are transmitted to offspring while those in somatic cells are not....
s in genes coding for
DNA repairDNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and Radiation can cause DNA damage, resulting in as many as 1...
enzymes cause hereditary cancer syndromes such as
xeroderma pigmentosumXeroderma pigmentosa, or XP, is an autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet light is deficient. This disorder leads to multiple basal cell carcinomas and other skin malignancies at a young age. In severe cases, it is necessary...
. 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 often derived from its substrate or the chemical reaction it catalyzes, with the word ending in
-ase. Examples are
lactaseLactase , a part of the β-galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers...
,
alcohol dehydrogenaseAlcohol dehydrogenases are a group of seven dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of NAD+ to NADH
...
and
DNA polymeraseA DNA polymerase is an enzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best-known for their role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand...
. 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
pHpH is a measure of the acidity or basicity of a solution. It is defined as the cologarithm of the activity of dissolved hydrogen ions . Hydrogen ion activity coefficients cannot be measured experimentally, so they are based on theoretical calculations...
, kinetic properties or immunologically. 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.
E.g. Glucose isomerase, used industrially to convert
glucoseGlucose , a monosaccharide also known as - grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate...
into the sweetener
fructoseFructose is a simple monosaccharide found in many foods. It is a white solid that dissolves readily in water. Honey, tree fruits, berries, melons, and some root vegetables, contain significant amounts of the fructose derivative sucrose...
, is a xylose isomerase
in vivo.
The
International Union of Biochemistry and Molecular BiologyThe International Union of Biochemistry and Molecular Biology is an international non-governmental organisation concerned with biochemistry and molecular biology...
have developed a
nomenclatureNomenclature refers to either a list of names and/or terms, or to the system of principles, procedures and terms related to naming - which is the assigning of a word or phrase to a particular object or property...
for enzymes, the
EC numberThe Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze....
s; each enzyme is described by a sequence of four numbers preceded by "EC".
The first number broadly classifies the enzyme based on its mechanism:
The top-level classification is
- EC 1 Oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another .- Reactions :...
s: catalyze oxidation/reduction reactions
- EC 2 Transferase
In biochemistry, a transferase is an enzyme that catalyzes the transfer of a functional group from one molecule to another . For example, an enzyme that catalyzed this reaction would be a transferase:In this example, A would be the donor, and B would be the acceptor...
s: transfer a functional groupIn organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part...
(e.g. a methyl or phosphate group)
- EC 3 Hydrolase
In biochemistry, a hydrolase is an enzyme that catalyzes the hydrolysis of a chemical bond. For example, an enzyme that catalyzed the following reaction is a hydrolase:-Nomenclature:...
s: catalyze the hydrolysisHydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
of various bonds
- EC 4 Lyase
In biochemistry, a lyase is an enzyme that catalyzes the breaking of various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or a new ring structure...
s: cleave various bonds by means other than hydrolysis and oxidation
- EC 5 Isomerase
In biochemistry, an isomerase is an enzyme that catalyzes the structural rearrangement of isomers. Isomerases thus catalyze reactions of the formwhere B is an isomer of A.-Nomenclature:...
s: catalyze isomerIn chemistry, isomers are compounds with the same molecular formula but different structural formulas. The word is derived from the Greek ισομερης, isomerès; isos = "equal", méros = "part"....
ization changes within a single molecule
- EC 6 Ligase
In biochemistry, a ligase is an enzyme that can catalyse the joining of two large molecules by forming a new chemical bond, usually with accompanying hydrolysis of a small chemical group pendant to one of the larger molecules...
s: join two molecules with covalent bondA covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms, or between atoms and other covalent bonds...
s
The complete nomenclature can be browsed at http://www.chem.qmul.ac.uk/iubmb/enzyme/.
Industrial applications
Enzymes are used in the
chemical industryThe chemical industry comprises the companies that produce industrial chemicals. It is central to modern world economy, converting raw materials into more than 70,000 different products.-Products:...
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. Consequently,
protein engineeringProtein engineering is the process of developing useful or valuable proteins. It is a young discipline, with much research currently taking place into the understanding of protein folding and protein recognition for protein design principles....
is an active area of research and involves attempts to create new enzymes with novel properties, either through rational design or
in vitro evolution. These efforts have begun to be successful, and a few enzymes have now been desiged "from scratch" to catalyse reactions that do not occur in nature.
| Application |
Enzymes used |
Uses |
| Food processing Food processing is the set of methods and techniques used to transform raw ingredients into food or to transform food into other forms for consumption by humans or animals either in the home or by the food processing industry...
|
Amylase An amylase is an enzyme that breaks starch down into sugar. Amylase is present in human saliva, where it begins the chemical process of digestion. Foods that contain much starch but little sugar, such as rice and potato, taste slightly sweet as they are chewed because amylase turns some of their...
s from fungiA fungus is any member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. The Fungi are classified as a kingdom that is separate from plants, animals and bacteria...
and plants. |
Production of sugars from starchStarch or amylum is a polysaccharide carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds.Starch is produced by all green plants as an energy store and is a major food source for humans....
, such as in making high-fructose corn syrup. In baking, catalyze breakdown of starch in the flourFlour is a powder made of cereal grains or roots. It is the main ingredient of bread, which is a staple food for many civilizations, making the availability of adequate supplies of flour a major economic and political issue at various times throughout history...
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 food Baby food is any food, other than breastmilk or infant formula, that is made for, specifically, infants, roughly between the ages of four months to two years. The food comes in multiple varieties and tastes, can be produced by many manufacturers, or may be table food that the rest of the family is...
s |
TrypsinTrypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin predominantly cleaves peptide chains at the carboxyl side of the amino acids lysine or arginine, except...
|
To predigest baby foods. |
Brewing industryBrewing is the production of alcoholic beverages and alcohol fuel through fermentation. The term is used for the production of beer, although the word "brewing" is also used to describe the fermentation process used to create wine and mead. It can also refer to the process of producing sake and soy...
|
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 maltMalting is a process applied to cereal grains, in which the grains are made to germinate by soaking in water and are then quickly halted from germinating further by drying/heating with hot air. Thus, malting is a combination of two processes: the sprouting process and the kiln-drying process...
. |
| Betaglucanases and arabinoxylanases |
Improve the wort and beer filtration characteristics. |
| Amyloglucosidase and pullulanases |
Low-calorie beerBeer is the world's oldest and most widely consumed alcoholic beverage and the third most popular drink overall after water and tea. It is produced by the brewing and fermentation of starches, mainly derived from cereal grains—most commonly malted barley, although wheat, maize , and rice are widely...
and adjustment of fermentability. |
| Proteases |
Remove cloudiness produced during storage of beers. |
|
Acetolactatedecarboxylase (ALDC) |
Increases fermentation efficiency by reducing diacetylDiacetyl is a natural byproduct of fermentation. It is a vicinal diketone with the molecular formula C 4H 6O 2...
formation. |
Fruit juicesJuice is a liquid naturally contained in fruit or vegetable tissue. Juice is prepared by mechanically squeezing or macerating fresh fruits or vegetables without the application of heat or solvents. For example, orange juice is the liquid extract of the fruit of the orange tree. Juice may be...
|
Cellulases, pectinases |
Clarify fruit juices |
Dairy industryA dairy is a facility for the extraction and processing of animal milk—mostly from cows or goats, but also from buffalo, sheep, horses or camels —for human consumption. Typically it is a farm or section of a farm that is concerned with the production of milk, butter and...
|
Rennin, derived from the stomachs of young ruminant animalsPhysiologically, a ruminant is a mammal of the order Artiodactyla that digests plant-based food by initially softening it within the animal's first stomach, known as the rumen, then regurgitating the semi-digested mass, now known as cud, and chewing it again. The process of rechewing the cud to...
(like calves and lambs). |
Manufacture of cheese, used to hydrolyze protein. |
| Microbially produced enzyme |
Now finding increasing use in the dairy industry. |
| Lipase A lipase is a soluble enzyme that catalyzes the hydrolysis of ester bonds in water–insoluble, lipid substrates. Lipases thus comprise a subclass of the esterases....
s |
Is implemented during the production of Roquefort cheese to enhance the ripening of the blue-mould cheeseDanish Blue cheese, also known as Danablu if it is made in Denmark, is a light, blue-veined cheese. This semi-soft creamery cheese is typically drum or block shaped and has a white to yellowish, slightly moist, edible rind...
. |
| Lactases |
Break down lactoseLactose is a sugar that is found most notably in milk. Lactose makes up around 2–8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey...
to glucoseGlucose , a monosaccharide also known as - grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate...
and galactose. |
| Meat tenderizers In cooking, tenderizing is a process to break down collagens in meat to make it more palatable for consumption.There are three basic forms:*Mechanical tenderization, such as pounding.*The tenderization that occurs through cooking, such as braising....
|
PapainPapain is a cysteine protease enzyme present in papaya and mountain papaya .-Structure:...
|
To soften meat for cooking. |
Starch industryStarch or amylum is a polysaccharide carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds.Starch is produced by all green plants as an energy store and is a major food source for humans....
|
Amylases, amyloglucosideases and glucoamylases |
Converts starchStarch or amylum is a polysaccharide carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds.Starch is produced by all green plants as an energy store and is a major food source for humans....
into glucoseGlucose , a monosaccharide also known as - grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate...
and various syrupsInverted or invert sugar syrup is a sucrose-based syrup, produced by splitting each sucrose disaccharide molecule into its component monomers, glucose and fructose. The splitting is achieved through the action of invertase , or an acid...
. |
| Glucose isomerase |
Converts glucose Glucose , a monosaccharide also known as - grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate...
into fructoseFructose is a simple monosaccharide found in many foods. It is a white solid that dissolves readily in water. Honey, tree fruits, berries, melons, and some root vegetables, contain significant amounts of the fructose derivative sucrose...
in production of high fructose syrups from starchy materials. These syrups have enhanced sweetening properties and lower calorific valuesThe calorie is a pre-SI metric unit of energy. The unit was first defined by Professor Nicolas Clément in 1824 as a unit of heat. This definition entered French and English dictionaries between 1841 and 1867. In most fields its use is archaic, having been replaced by the SI unit of energy, the joule...
than sucrose for the same level of sweetness. |
Paper industryPaper is thin material mainly used for writing upon, printing upon or for packaging. It is produced by pressing together moist fibers, typically cellulose pulp derived from wood, rags or grasses, and drying them into flexible sheets....
|
Amylase An amylase is an enzyme that breaks starch down into sugar. Amylase is present in human saliva, where it begins the chemical process of digestion. Foods that contain much starch but little sugar, such as rice and potato, taste slightly sweet as they are chewed because amylase turns some of their...
s, XylanaseXylanase is the name given to a class of enzymes which degrade the linear polysaccharide beta-1,4-xylan into xylose, thus breaking down hemicellulose, one of the major components of plant cell walls....
s, CellulaseCellulase refers to a class of enzymes produced chiefly by fungi, bacteria, and protozoans that catalyze the cellulolysis of cellulose. However, there are also cellulases produced by other types of organisms such as plants and animals. Several different kinds of cellulases are known, which differ...
s and ligninaseLigninase is the original term encompassing many different types of oxidative, extracellular fungal enzymes which catalyze the breakdown of Lignin which is commonly found in the cell walls of plants. Instead of the term ligninase, the term lignin-modifying enzymes should be used, since these...
s |
Degrade starch to lower viscosityViscosity is a measure of the resistance of a fluid which is being deformed by either shear stress or extensional stress. In everyday terms , viscosity is "thickness." Thus, water is "thin," having a lower viscosity, while honey is "thick," having a higher viscosity...
, aiding sizingSizing or size is a substance that is applied to materials as a protecting glaze, filler, or lubricant. It is used to change surface properties in papermaking, gilding, and the manufacture of textiles and fiberglass.- Papermaking :...
and coating paper. Xylanases reduce bleach required for decolorising; cellulases smooth fibers, enhance water drainage, and promote ink removal; lipases reduce pitch and lignin-degrading enzymes remove ligninLignin or lignen is a complex chemical compound most commonly derived from wood, and an integral part of the secondary cell walls of plants and some algae. The term was introduced in 1819 by de Candolle and is derived from the Latin word lignum, meaning wood...
to soften paper. |
BiofuelBiofuel is defined as solid, liquid or gaseous fuel obtained from lifeless or living biological material and is similar to fossil fuels, which are derived from long dead biological material. Also, various plants and plant-derived materials are used for biofuel manufacturing...
industry |
Cellulase Cellulase refers to a class of enzymes produced chiefly by fungi, bacteria, and protozoans that catalyze the cellulolysis of cellulose. However, there are also cellulases produced by other types of organisms such as plants and animals. Several different kinds of cellulases are known, which differ...
s |
Used to break down cellulose into sugars that can be fermented (see cellulosic ethanolCellulosic ethanol is a biofuel produced from wood, grasses, or the non-edible parts of plants.It is a type of biofuel produced from lignocellulose, a structural material that comprises much of the mass of plants. Lignocellulose is composed mainly of cellulose, hemicellulose and lignin...
). |
| Ligninase Ligninase is the original term encompassing many different types of oxidative, extracellular fungal enzymes which catalyze the breakdown of Lignin which is commonly found in the cell walls of plants. Instead of the term ligninase, the term lignin-modifying enzymes should be used, since these...
s |
Use of ligninLignin or lignen is a complex chemical compound most commonly derived from wood, and an integral part of the secondary cell walls of plants and some algae. The term was introduced in 1819 by de Candolle and is derived from the Latin word lignum, meaning wood...
waste |
| Biological detergent A biological detergent is a laundry detergent that contains enzymes. The description is commonly used in the United Kingdom, where other washing detergents are described as "non-biological"...
|
Primarily protease A protease breaks down proteins. A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein...
s, produced in an extracellularIn cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
form from bacteriaThe bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
|
Used for presoak conditions and direct liquid applications helping with removal of protein stains from clothes. |
| Amylase An amylase is an enzyme that breaks starch down into sugar. Amylase is present in human saliva, where it begins the chemical process of digestion. Foods that contain much starch but little sugar, such as rice and potato, taste slightly sweet as they are chewed because amylase turns some of their...
s |
Detergents for machine dish washing to remove resistant starch residues. |
| Lipase A lipase is a soluble enzyme that catalyzes the hydrolysis of ester bonds in water–insoluble, lipid substrates. Lipases thus comprise a subclass of the esterases....
s |
Used to assist in the removal of fatty and oily stains. |
| Cellulase Cellulase refers to a class of enzymes produced chiefly by fungi, bacteria, and protozoans that catalyze the cellulolysis of cellulose. However, there are also cellulases produced by other types of organisms such as plants and animals. Several different kinds of cellulases are known, which differ...
s |
Used in biological fabric conditioners. |
| Contact lens cleaners A contact lens is a corrective, cosmetic, or therapeutic lens usually placed on the cornea of the eye...
|
Proteases |
To remove proteins on contact lens A contact lens is a corrective, cosmetic, or therapeutic lens usually placed on the cornea of the eye...
to prevent infections. |
Rubber industryNatural rubber is an elastomer that was originally derived from a milky colloidal suspension, or latex, found in the sap of some plants. The purified form of natural rubber is the chemical polyisoprene, which can also be produced synthetically...
|
CatalaseCatalase is a common enzyme found in nearly all living organisms which are exposed to oxygen, where it functions to catalyze the decomposition of hydrogen peroxide to water and oxygen...
|
To generate oxygenOxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
from peroxideA peroxide is a compound containing an oxygen-oxygen single bond. The simplest stable peroxide is hydrogen peroxide. Superoxides, dioxygenyls, ozones and ozonides compound are considered separately.- Organic chemistry :...
to convert latexLatex refers generically to a stable dispersion of polymer microparticles in an aqueous medium. Latexes may be natural or synthetic. Latex as found in nature is a milky sap-like fluid within many plants that coagulates on exposure to air. It is a complex emulsion in which proteins, alkaloids,...
into foam rubber. |
| Photographic industry Photography is the process, activity and art of creating still or moving pictures by recording radiation on a sensitive medium, such as a photographic film, or an electronic sensor...
|
Protease A protease breaks down proteins. A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein...
(ficin) |
Dissolve gelatinGelatin is a translucent, colorless, odorless, brittle, nearly tasteless solid substance, derived from the collagen inside animals' skin and bones. It is commonly used as a gelling agent in food, pharmaceuticals, photography, and cosmetic manufacturing. Substances containing gelatin or functioning...
off scrap filmPhotographic film is a sheet of plastic coated with an emulsion containing light-sensitive silver halide salts with variable crystal sizes that determine the sensitivity, contrast and resolution of the film...
, allowing recovery of its silverSilver is a chemical element with the chemical symbol Ag and atomic number 47. A soft, white, lustrous transition metal, it has the highest electrical conductivity of any element and the highest thermal conductivity of any metal...
content. |
Molecular biologyMolecular biology is the study of biology at a molecular level. The field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
|
Restriction enzymeA restriction enzyme is an enzyme that cuts double-stranded or single stranded DNA at specific recognition nucleotide sequences known as restriction sites. Such enzymes, found in bacteria and archaea, are thought to have evolved to provide a defense mechanism against invading viruses...
s, DNA ligaseIn molecular biology, DNA ligase is a special type of ligase that can link together two DNA strands that have double-strand break...
and polymerases |
Used to manipulate DNA in genetic engineeringGenetic engineering, recombinant DNA technology, genetic modification/manipulation and gene splicing are terms that apply to the direct manipulation of an organism's genes. Genetic engineering is different from traditional breeding, where the organism's genes are manipulated indirectly...
, important in pharmacologyPharmacology is the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and exogenous chemicals that alter normal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals...
, agricultureAgriculture is the production of food and goods through farming and forestry. Agriculture was the key development that led to the rise of human civilization, with the husbandry of domesticated animals and plants creating food surpluses that enabled the development of more densely populated and...
and medicineMedicine is the art and science of healing. It encompasses a range of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
. Essential for restriction digestionA restriction enzyme is an enzyme that cuts double-stranded or single stranded DNA at specific recognition nucleotide sequences known as restriction sites. Such enzymes, found in bacteria and archaea, are thought to have evolved to provide a defense mechanism against invading viruses...
and the polymerase chain reactionIn molecular biology, the polymerase chain reaction is a technique to amplify a single or few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence...
. Molecular biology is also important in forensic science. |
See also
- List of enzymes
- Enzyme product
In biochemistry, a product is something "manufactured" by an enzyme from its substrate. For example the products of Lactase are Galactose and Glucose, which are produced from the substrate Lactose.....
- Enzyme substrate
- Enzyme assay
Enzyme assays are laboratory methods for measuring enzymatic activity. They are vital for the study of enzyme kinetics and enzyme inhibition.-Enzyme units:...
- Enzyme catalysis
Enzyme catalysis is the catalysis of chemical reactions by specialized proteins known as enzymes. Catalysis of biochemical reactions in the cell is vital due to the very low reaction rates of the uncatalysed reactions....
- Protein dynamics
- The Proteolysis Map
The Proteolysis MAP is an integrated web resource focused on proteases.-Rationale:PMAP is to aid the protease researchers in reasoning about proteolytic networks and metabolic pathways.-History & Funding:...
- RNA Biocatalysis
- SUMO enzymes
SUMO enzymatic cascade catalyzes the dynamic posttranslational modification process of sumoylation...
- Ki Database
The Ki Database is a public domain database of published binding affinities of drugs and chemical compounds for receptors, neurotransmitter transporters, ion channels, and enzymes...
- Proteonomics and protein engineering
Protein engineering is the process of developing useful or valuable proteins. It is a young discipline, with much research currently taking place into the understanding of protein folding and protein recognition for protein design principles....
- Immobilized enzyme
An immobilized enzyme is an enzyme which is attached to an inert, insoluble material such as calcium alginate . This can provide increased resistance to changes in conditions such as pH or temperature...
- Kinetic Perfection
Kinetic perfection, also known as catalytic perfection, refers to enzymes that are diffusion-limited; that is, the reaction they catalyze occurs as quickly as the reactants diffuse to the enzyme...
- Enzyme engineering
Enzyme engineering is the application of modifying an enzyme's structure or modifying the catalytic activity of isolated enzymes to produce new metabolites, to allow new pathways for reactions to occur, or to convert from some certain compounds into others...
Further reading
Etymology and history
, A history of early enzymology.
Enzyme structure and mechanism
- Page, M. I., and Williams, A. (Eds.). Enzyme Mechanisms. Royal Society of Chemistry, 1987. ISBN 0-85186-947-5.
- Bugg, T. Introduction to Enzyme and Coenzyme Chemistry. (2nd edition), Blackwell Publishing Limited, 2004. ISBN 1-40511-452-5.
- Warshel, A. Computer Modeling of Chemical Reactions in enzymes and Solutions. John Wiley & Sons Inc., 1991. ISBN 0-471-18440-3.
Thermodynamics
Kinetics and inhibition
- Cornish-Bowden, Athel. Fundamentals of Enzyme Kinetics. (3rd edition), Portland Press, 2004. ISBN 1-85578-158-1.
- Segel Irwin H. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems. (New Ed edition), Wiley-Interscience, 1993. ISBN 0-471-30309-7.
- Baynes, John W. Medical Biochemistry. (2nd edition), Elsevier-Mosby, 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". Chapter of the on-line textbook Introduction to Genes and Disease from the NCBI.
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
External links