TheInfoList

Enzymes () are
protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...

s that act as
biological Biology is the natural science Natural science is a branch of science Science (from the Latin word ''scientia'', meaning "knowledge") is a systematic enterprise that Scientific method, builds and Taxonomy (general), organizes knowl ...

catalyst Catalysis () is the process of increasing the rate of a chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substance A chemical substance is a form of matter In cla ...

s (biocatalysts). Catalysts accelerate
chemical reactions A chemical reaction is a process that leads to the chemical transformation of one set of chemical substance A chemical substance is a form of matter In classical physics and general chemistry, matter is any substance that has mass and ...

. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as
products Product may refer to: Business * Product (business), an item that serves as a solution to a specific consumer problem. * Product (project management), a deliverable or set of deliverables that contribute to a business solution Mathematics * Produc ...
. Almost all in the cell need
enzyme catalysis Enzyme catalysis is the increase in the rate of a process A process is a series or set of activities that interact to produce a result; it may occur once-only or be recurrent or periodic. Things called a process include: Business and managem ...

in order to occur at rates fast enough to sustain life.
Metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence ...
s depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their
amino acid Amino acids are organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of organic compounds are known. The study of the properties, reactions, a ...

sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are , called ribozymes. Enzymes' specificity comes from their unique . Like all catalysts, enzymes increase the
reaction rate The reaction rate or rate of reaction is the speed at which a chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substance A chemical substance is a form of matter In c ...
by lowering its
activation energy In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they undergo during ...

. Some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is
orotidine 5'-phosphate decarboxylase Orotidine 5'-phosphate decarboxylase (OMP decarboxylase) or orotidylate decarboxylase is an enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme co ...
, which allows a reaction that would otherwise take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, nor do they alter the
equilibrium List of types of equilibrium, the condition of a system in which all competing influences are balanced, in a wide variety of contexts. Equilibrium may also refer to: Film and television * Equilibrium (film), ''Equilibrium'' (film), a 2002 scien ...
of a reaction. Enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules: inhibitors are molecules that decrease enzyme activity, and activators are molecules that increase activity. Many therapeutic
drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffl ...

s and
poison In biology, poisons are Chemical substance, substances that can cause death, injury or harm to organs, Tissue (biology), tissues, Cell (biology), cells, and DNA usually by chemical reactions or other activity (chemistry), activity on the molecul ...

s are enzyme inhibitors. An enzyme's activity decreases markedly outside its optimal
temperature Temperature ( ) is a physical quantity that expresses hot and cold. It is the manifestation of thermal energy Thermal radiation in visible light can be seen on this hot metalwork. Thermal energy refers to several distinct physical concept ...

and , and many enzymes are (permanently) denatured when exposed to excessive heat, losing their structure and catalytic properties. Some enzymes are used commercially, for example, in the synthesis of
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
. Some household products use enzymes to speed up chemical reactions: enzymes in biological washing powders break down protein, starch or
fat In nutrition Nutrition is the biochemical Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided ...

stains on clothes, and enzymes in
meat tenderizer A meat tenderizer, meat mallet, or meat pounder is a hand-powered tool used to tenderize slabs of meat in the preparation for cooking. Although a meat tenderizer can be made out of virtually any object, there are three types manufactured specif ...

break down proteins into smaller molecules, making the meat easier to chew.

# Etymology and history

By the late 17th and early 18th centuries, the digestion of
meat Meat is animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiratio ...

by stomach secretions and the conversion of
starch Starch or amylum is a polymeric A polymer (; Greek '' poly-'', "many" + '' -mer'', "part") is a substance Substance may refer to: * Substance (Jainism), a term in Jain ontology to denote the base or owner of attributes * Chemical substance ...
to
sugar Sugar is the generic name for sweet-tasting, soluble carbohydrate is a disaccharide A disaccharide (also called a double sugar or ''biose'') is the sugar formed when two monosaccharides are joined by glycosidic linkage. Like monosacc ...

s by plant extracts and
saliva Saliva (commonly referred to as spit) is an extracellular fluid In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including t ...
were known but the mechanisms by which these occurred had not been identified. French chemist
Anselme Payen Anselme Payen (; 6 January 1795 – 12 May 1871) was a French chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist A scientist is a person who conducts Scientific m ...

was the first to discover an enzyme,
diastase A diastase (; from Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approxim ...
, in 1833. A few decades later, when studying the
fermentation Fermentation is a metabolic Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life Life is a characteristic that distinguishes physical entities that have biological processes, such as Cell signalin ...
of sugar to
alcohol In chemistry, alcohol is an organic compound that carries at least one hydroxyl functional group (−OH) bound to a Saturated and unsaturated compounds, saturated carbon atom. The term alcohol originally referred to the primary alcohol ethan ...

by
yeast Yeasts are eukaryotic Eukaryotes () are organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular ...

,
Louis Pasteur Louis Pasteur (, ; 27 December 1822 – 28 September 1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, fermentation, microbial fermentation, and pasteurization. His research in chemi ...

concluded that this fermentation was caused by a vital force contained within the yeast cells called "ferments", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells." In 1877, German physiologist
Wilhelm Kühne Wilhelm Friedrich Kühne (28 March 183710 June 1900) was a German physiologist. Born in Hamburg en, Hamburgian(s) , timezone1 = Central European Time, CET , utc_offset1 = +1 , timezone1_DST ...
(1837–1900) first used the term ''
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...
'', which comes from
Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approximately 10.7 million as of ...
ἔνζυμον, "leavened" or "in yeast", to describe this process. The word ''enzyme'' was used later to refer to nonliving substances such as
pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides. It is produced in the gastric chief cells of the stomach lining and is one of the main digestive enzymes in the digestive systems of humans and many other animals, where ...

, and the word ''ferment'' was used to refer to chemical activity produced by living organisms.
Eduard Buchner Eduard Buchner (20 May 1860 – 13 August 1917) was a German chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist A scientist is a person who conducts Scientific meth ...
submitted his first paper on the study of yeast extracts in 1897. In a series of experiments at the
University of Berlin Humboldt University of Berlin (german: Humboldt-Universität zu Berlin, abbreviated HU Berlin) is a public In public relations and communication science, publics are groups of individual people, and the public (a.k.a. the general public) ...
, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose "
zymase Zymase is an enzyme Enzymes () are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one location to ...
". In 1907, he received the
Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "MD ...
for "his discovery of cell-free fermentation". Following Buchner's example, enzymes are usually named according to the reaction they carry out: the suffix ''
-ase The suffix In linguistics Linguistics is the science, scientific study of language. It encompasses the analysis of every aspect of language, as well as the methods for studying and modeling them. The traditional areas of linguistic anal ...
'' is combined with the name of the
substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached **Substrate (locomotion), the surface over which an organism loco ...
(e.g.,
lactase Lactase is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme conve ...

is the enzyme that cleaves
lactose Lactose, a disaccharide A disaccharide (also called a double sugar or ''biose'') is the sugar Sugar is the generic name for sweet-tasting, soluble carbohydrate is a disaccharide A disaccharide (also called a double sugar or ''biose ...

) or to the type of reaction (e.g.,
DNA polymerase A DNA polymerase is a member of a family of enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into different molecules ...

forms DNA polymers). The biochemical identity of enzymes was still unknown in the early 1900s. Many scientists observed that enzymatic activity was associated with proteins, but others (such as Nobel laureate ) argued that proteins were merely carriers for the true enzymes and that proteins ''per se'' were incapable of catalysis. quoted in In 1926, James B. Sumner showed that the enzyme
urease Ureases (), functionally, belong to the superfamily SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially ...

was a pure protein and crystallized it; he did likewise for the enzyme
catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyst, catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in prote ...

in 1937. The conclusion that pure proteins can be enzymes was definitively demonstrated by
John Howard Northrop John Howard Northrop (July 5, 1891 – May 27, 1987) was an American biochemist Biochemists are scientists who are trained in biochemistry Biochemistry or biological chemistry, is the study of chemical processes within and relating to liv ...

and , who worked on the digestive enzymes
pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides. It is produced in the gastric chief cells of the stomach lining and is one of the main digestive enzymes in the digestive systems of humans and many other animals, where ...

(1930),
trypsin Trypsin () is a serine protease Serine proteases (or serine endopeptidases) are s that cleave s in s. serves as the at the (enzyme's) . They are found ubiquitously in both and . Serine proteases fall into two broad categories based on ...
and
chymotrypsin Chymotrypsin (, chymotrypsins A and B, alpha-chymar ophth, avazyme, chymar, chymotest, enzeon, quimar, quimotrase, alpha-chymar, alpha-chymotrypsin A, alpha-chymotrypsin) is a digestive enzyme Digestive may refer to: Biology *Digestion Dige ...

. These three scientists were awarded the 1946 Nobel Prize in Chemistry. The discovery that enzymes could be crystallized eventually allowed their structures to be solved by
x-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract into many specific directions. By measurin ...

. This was first done for
lysozyme Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, is an antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an ...

, an enzyme found in tears, saliva and
egg white Egg white is the clear liquid (also called the albumen or the glair/glaire) contained within an egg An egg is the organic vessel containing the in which an develops until it can survive on its own, at which point the animal hatches. An ...
s that digests the coating of some bacteria; the structure was solved by a group led by
David Chilton Phillips David Chilton Phillips, Baron Phillips of Ellesmere, KBE, FRS (7 March 1924 – 23 February 1999) was a pioneering, British structural biologist and an influential figure in science and government. Research Phillips lead the team which determ ...
and published in 1965. This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail.

# Classification and nomenclature

Enzymes can be classified by two main criteria: either
amino acid sequence Protein primary structure is the Biomolecular structure#Primary structure, linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the Amine, amino-terminal (N) end to the ...

similarity (and thus evolutionary relationship) or enzymatic activity. Enzyme activity. An enzyme's name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in ''-ase''. Examples are
lactase Lactase is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme conve ...

,
alcohol dehydrogenase Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH. ...

and
DNA polymerase A DNA polymerase is a member of a family of enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into different molecules ...

. Different enzymes that catalyze the same chemical reaction are called
isozymesIsozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. These enzymes usually display different kinetic parameters (e.g. different Mic ...
. The
International Union of Biochemistry and Molecular Biology The International Union of Biochemistry and Molecular Biology (IUBMB) is an international non-governmental organisation concerned with biochemistry and molecular biology. Formed in 1955 as the International Union of Biochemistry (IUB), the union ...
have developed a
nomenclature Nomenclature (, ) is a system A system is a group of interacting Interaction is a kind of action that occurs as two or more objects have an effect upon one another. The idea of a two-way effect is essential in the concept of interaction, a ...

for enzymes, the EC numbers (for "Enzyme Commission"). Each enzyme is described by "EC" followed by a sequence of four numbers which represent the hierarchy of enzymatic activity (from very general to very specific). That is, the first number broadly classifies the enzyme based on its mechanism while the other digits add more and more specificity. The top-level classification is: *EC 1,
Oxidoreductase In biochemistry, an oxidoreductase is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), subst ...
s: catalyze
oxidation Redox (reduction–oxidation, pronunciation: or ) is a type of chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substance A chemical substance is a form of matter ...

/reduction reactions *EC 2,
Transferase '' complexed with α-amanitin (in red). Despite the use of the term "polymerase," RNA polymerases are classified as a form of nucleotidyl transferase. A transferase is any one of a class of enzymes that enact the transfer of specific functional ...
s: transfer a
functional group In organic chemistry, a functional group is a substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions re ...
(''e.g.'' a methyl or phosphate group) *EC 3,
Hydrolase Hydrolase is a class of enzyme that commonly perform as biochemical catalysts that use water to break a chemical bond, which typically results in dividing a larger molecule into smaller molecules. Some common examples of hydrolase enzymes are este ...
s: catalyze the
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution Substitution may refer to: Arts and media *Chord substitution, in music, swapping one chord fo ...

of various bonds *EC 4,
Lyase In biochemistry Biochemistry or biological chemistry, is the study of es within and relating to living s. A sub-discipline of both and , biochemistry may be divided into three fields: , and . Over the last decades of the 20th century, bio ...
s: cleave various bonds by means other than hydrolysis and oxidation *EC 5,
Isomerase''Isomerases'' are a general class of enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates ...

s: catalyze
isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulas — that is, same number of atoms of each element (chemistry), element — but distinct arrangements of atoms in space. Isomerism is existence or possibil ...

ization changes within a single molecule *EC 6,
Ligase In biochemistry Biochemistry or biological chemistry, is the study of es within and relating to living s. A sub-discipline of both and , biochemistry may be divided into three fields: , and . Over the last decades of the 20th century, b ...

s: join two molecules with
covalent bond A covalent bond is a chemical bond that involves the sharing of electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs, and the stable balance of attractive and repulsive forces between atoms, when they s ...
s. *EC 7,
TranslocaseTranslocase is a general term for a protein that assists in moving another molecule, usually across a cell membrane. These Enzyme, enzymes catalyze the movement of ions or molecules across membranes or their separation within membranes. The reaction ...
s: catalyze the movement of ions or molecules across membranes, or their separation within membranes. These sections are subdivided by other features such as the substrate, products, and
chemical mechanism In chemistry Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science that covers the Chemical element, elements that make up matter to the chemical compound, compounds composed of atoms, ...
. An enzyme is fully specified by four numerical designations. For example,
hexokinase A hexokinase is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the e ...
(EC 2.7.1.1) is a transferase (EC 2) that adds a phosphate group (EC 2.7) to a hexose sugar, a molecule containing an alcohol group (EC 2.7.1). Sequence similarity. EC categories do not reflect sequence similarity. For instance, two ligases of the same EC number that catalyze exactly the same reaction can have completely different sequences. Independent of their function, enzymes, like any other proteins, have been classified by their sequence similarity into numerous families. These families have been documented in dozens of different protein and protein family databases such as
Pfam Pfam is a database of protein families A protein family is a group of evolutionarily-related proteins. In many cases a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. Th ...
.

# Structure

Enzymes are generally
globular protein Globular proteins or spheroproteins are spherical ("globe-like") protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max ...
s, acting alone or in larger complexes. The sequence of the amino acids specifies the structure which in turn determines the catalytic activity of the enzyme. Although structure determines function, a novel enzymatic activity cannot yet be predicted from structure alone. Enzyme structures unfold ( denature) when heated or exposed to chemical denaturants and this disruption to the structure typically causes a loss of activity. Enzyme denaturation is normally linked to temperatures above a species' normal level; as a result, enzymes from bacteria living in volcanic environments such as
hot spring A hot spring, hydrothermal spring, or geothermal spring is a spring Spring(s) may refer to: Common uses * Spring (season), a season of the year * Spring (device), a mechanical device that stores energy * Spring (hydrology), a natural source of w ...

s are prized by industrial users for their ability to function at high temperatures, allowing enzyme-catalysed reactions to be operated at a very high rate. Enzymes are usually much larger than their substrates. Sizes range from just 62 amino acid residues, for the
monomer In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in th ...

of
4-oxalocrotonate tautomerase 4-Oxalocrotonate tautomerase (EC 5.3.2.-4-OT) 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 catabolism, catabolizes toluen ...
, to over 2,500 residues in the animal
fatty acid synthase Fatty acid synthase (FAS) is an enzyme that in humans is encoded by the ''FASN'' gene. Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis. It is not a single enzyme but a whole enzymatic system composed of two identi ...

. Only a small portion of their structure (around 2–4 amino acids) is directly involved in catalysis: the catalytic site. This catalytic site is located next to one or more
binding site Binding may refer to: Computing * Binding, associating a network socket Network and networking may refer to: Arts, entertainment, and media * Network (1976 film), ''Network'' (1976 film), a 1976 American film * Network (2019 film), ''Network'' ...
s where residues orient the substrates. The catalytic site and binding site together compose the enzyme's . The remaining majority of the enzyme structure serves to maintain the precise orientation and dynamics of the active site. In some enzymes, no amino acids are directly involved in catalysis; instead, the enzyme contains sites to bind and orient catalytic cofactors. Enzyme structures may also contain
allosteric site 300px, Allosteric regulation of an enzyme In biochemistry Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be ...
s where the binding of a small molecule causes a
conformational change In biochemistry Biochemistry or biological chemistry, is the study of es within and relating to living s. A sub-discipline of both and , biochemistry may be divided into three fields: , and . Over the last decades of the 20th century, bi ...

that increases or decreases activity. A small number of
RNA Ribonucleic acid (RNA) is a polymer A polymer (; Greek ''wikt:poly-, poly-'', "many" + ''wikt:-mer, -mer'', "part") is a Chemical substance, substance or material consisting of very large molecules, or macromolecules, composed of many Re ...
-based biological catalysts called
ribozyme Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonst ...

s exist, which again can act alone or in complex with proteins. The most common of these is the
ribosome Ribosomes ( ), also called Palade granules, are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (mRNA translation). Ribosomes link amino acids ...

which is a complex of protein and catalytic RNA components.

# Mechanism

## Substrate binding

Enzymes must bind their substrates before they can catalyse any chemical reaction. Enzymes are usually very specific as to what substrates they bind and then the chemical reaction catalysed. Specificity is achieved by binding pockets with complementary shape, charge and
hydrophilic A hydrophile is a molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an electrically neutral group of two or more atoms ...
/
hydrophobic In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence ...
characteristics to the substrates. Enzymes can therefore distinguish between very similar substrate molecules to be , regioselective and
stereospecific In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in the ...
. Some of the enzymes showing the highest specificity and accuracy are involved in the copying and of the
genome In the fields of molecular biology Molecular biology is the branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, M ...

. Some of these enzymes have "
proof-reading Proofreading is the reading (activity), reading of a galley proof or an electronic copy of a publication to find and correct production errors of writing, text or Graphic arts, art. Proofreading is the final step in the editorial cycle before pu ...
" mechanisms. Here, an enzyme such as
DNA polymerase A DNA polymerase is a member of a family of enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into different molecules ...

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 mammalian polymerases. Similar proofreading mechanisms are also found in
RNA polymerase In molecular biology Molecular biology is the branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, molecular synthesis, modification, m ...

,
aminoacyl tRNA synthetase An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an that attaches the appropriate onto its corresponding . It does so by catalyzing the of a specific cognate amino acid or its precursor to one of all its compatible cogn ...
s and
ribosome Ribosomes ( ), also called Palade granules, are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (mRNA translation). Ribosomes link amino acids ...

s. Conversely, some enzymes display
enzyme promiscuityEnzyme promiscuity is the ability of an enzyme to catalyse a fortuitous side reaction in addition to its main reaction. Although enzymes are remarkably specific catalysts, they can often perform side reactions in addition to their main, native cataly ...
, having broad specificity and acting on a range of different physiologically relevant substrates. Many enzymes possess small side activities which arose fortuitously (i.e. neutrally), which may be the starting point for the evolutionary selection of a new function.

### "Lock and key" model

To explain the observed specificity of enzymes, in 1894
Emil Fischer Hermann Emil Louis Fischer FRS FRSE FCS (c; ; 9 October 185215 July 1919) was a German chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist A scientist is a person ...

proposed that 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. This early model explains enzyme specificity, but fails to explain the stabilization of the transition state that enzymes achieve.

### Induced fit model

In 1958, Daniel Koshland suggested a modification to the lock and key model: since enzymes are rather flexible structures, the active site is continuously reshaped by interactions with the substrate as the substrate interacts with the enzyme. As a result, the substrate does not simply bind to a rigid active site; the amino acid side-chains that make up the active site are molded into the precise positions that enable the enzyme to perform its catalytic function. In some cases, such as glycosidases, the substrate
molecule A molecule is an electrically Electricity is the set of physical phenomena associated with the presence and motion Image:Leaving Yongsan Station.jpg, 300px, Motion involves a change in position In physics, motion is the phenomenon ...

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 distribution is determined. Induced fit may enhance the fidelity of molecular recognition in the presence of competition and noise via the
conformational proofreadingConformational proofreading or conformational selection is a general mechanism of molecular recognition systems in which introducing a structural mismatch between a molecular recognizer and its target, or an energetic barrier, enhances the recogniti ...
mechanism.

## Catalysis

Enzymes can accelerate reactions in several ways, all of which lower the
activation energy In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they undergo during ...

(ΔG,
Gibbs free energy In thermodynamics Thermodynamics is a branch of physics that deals with heat, Work (thermodynamics), work, and temperature, and their relation to energy, entropy, and the physical properties of matter and radiation. The behavior of these qua ...
) # By stabilizing the transition state: #* Creating an environment with a charge distribution complementary to that of the transition state to lower its energy # By providing an alternative reaction pathway: #* Temporarily reacting with the substrate, forming a covalent intermediate to provide a lower energy transition state # By destabilising the substrate ground state: #* Distorting bound substrate(s) into their transition state form to reduce the energy required to reach the transition state #* By orienting the substrates into a productive arrangement to reduce the reaction
entropy Entropy is a scientific concept as well as a measurable physical property that is most commonly associated with a state of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodynamic ...

change (the contribution of this mechanism to catalysis is relatively small) Enzymes may use several of these mechanisms simultaneously. For example,
protease A protease (also called a peptidase or proteinase) is an enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into differe ...

s such as
trypsin Trypsin () is a serine protease Serine proteases (or serine endopeptidases) are s that cleave s in s. serves as the at the (enzyme's) . They are found ubiquitously in both and . Serine proteases fall into two broad categories based on ...
perform covalent catalysis using a
catalytic triad A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, lipas ...

, stabilise charge build-up on the transition states using an , complete
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution Substitution may refer to: Arts and media *Chord substitution, in music, swapping one chord fo ...

using an oriented water substrate.

## Dynamics

Enzymes are not rigid, static structures; instead they have complex internal dynamic motions – that is, movements of parts of the enzyme's structure such as individual amino acid residues, groups of residues forming a protein loop or unit of
secondary structure Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an elect ...
, or even an entire
protein domain A protein domain is a region of the protein's Peptide, polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact protein folding, folded three-dimensional structure. Many proteins consist ...
. These motions give rise to a conformational ensemble of slightly different structures that interconvert with one another at
equilibrium List of types of equilibrium, the condition of a system in which all competing influences are balanced, in a wide variety of contexts. Equilibrium may also refer to: Film and television * Equilibrium (film), ''Equilibrium'' (film), a 2002 scien ...
. Different states within this ensemble may be associated with different aspects of an enzyme's function. For example, different conformations of the enzyme
dihydrofolate reductase Dihydrofolate reductase, or DHFR, is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), sub ...
are associated with the substrate binding, catalysis, cofactor release, and product release steps of the catalytic cycle, consistent with
catalytic resonance theoryIn chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they undergo ...
.

## Substrate presentation

Substrate presentationSubstrate presentation is a biological process that activates a protein. The protein is sequestered away from its substrate and then activated by release and exposure of the protein to its substrate. A Substrate (chemistry), substrate is typically th ...
is a process where the enzyme is sequestered away from its substrate. Enzymes can be sequestered to the plasma membrane away from a substrate in the nucleus or cytosol. Or within the membrane, an enzyme can be sequestered into lipid rafts away from its substrate in the disordered region. When the enzyme is released it mixes with its substrate. Alternatively, the enzyme can be sequestered near its substrate to activate the enzyme. For example, the enzyme can be soluble and upon activation bind to a lipid in the plasma membrane and then act upon molecules in the plasma membrane.

## Allosteric modulation

Allosteric sites are pockets on the enzyme, distinct from the active site, that bind to molecules in the cellular environment. These molecules then cause a change in the conformation or dynamics of the enzyme that is transduced to the active site and thus affects the reaction rate of the enzyme. In this way, allosteric interactions can either inhibit or activate enzymes. Allosteric interactions with metabolites upstream or downstream in an enzyme's metabolic pathway cause
feedback Feedback occurs when outputs of a system are routed back as inputs as part of a chain A chain is a assembly of connected pieces, called links, typically made of metal, with an overall character similar to that of a in that it is flexib ...

regulation, altering the activity of the enzyme according to the
flux Flux describes any effect that appears to pass or travel (whether it actually moves or not) through a surface or substance. Flux is a concept in applied mathematics and vector calculus which has many applications to physics. For transport ph ...
through the rest of the pathway.

# Cofactors

Some enzymes do not need additional components to show full activity. Others require non-protein molecules called cofactors to be bound for activity. Cofactors can be either
inorganic In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they under ...
(e.g.,
metal ions A metal (from Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approximately 10.7 mil ...
and iron-sulfur clusters) or
organic compounds In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they undergo during ...
(e.g., and
heme Heme, or haem, is a precursor Precursor or Precursors may refer to: *Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was comp ...

). These cofactors serve many purposes; for instance, metal ions can help in stabilizing nucleophilic species within the active site. Organic cofactors can be either
coenzyme A cofactor is a non-protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 195 ...
s, which are released from the enzyme's active site during the reaction, or prosthetic groups, which are tightly bound to an enzyme. Organic prosthetic groups can be covalently bound (e.g.,
biotin Biotin, also called vitamin B7, is one of the B vitamins B vitamins are a class of water-soluble vitamin A vitamin is an organic molecule , CH4; is among the simplest organic compounds. In chemistry, organic compounds are generally any c ...

in enzymes such as
pyruvate carboxylase Pyruvate carboxylase (PC) encoded by the gene PC is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate ...
). An example of an enzyme that contains a cofactor is
carbonic anhydrase The carbonic anhydrases (or carbonate dehydratases) form a family of enzymes that catalyst, catalyze the interconversion between carbon dioxide and water and the Dissociation (chemistry), dissociated ions of carbonic acid (i.e. bicarbonate and ...

, which uses a zinc cofactor bound as part of its active site. These tightly bound ions or molecules are usually found in the active site and are involved in catalysis. For example, flavin and heme cofactors are often involved in
redox Redox (reduction–oxidation, pronunciation: or ) is a type of chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substance A chemical substance is a form of matter ...

reactions. Enzymes that require a cofactor but do not have one bound are called ''apoenzymes'' or ''apoproteins''. An enzyme together with the cofactor(s) required for activity is called a ''holoenzyme'' (or haloenzyme). The term ''holoenzyme'' can also be applied to enzymes that contain multiple protein subunits, such as the
DNA polymerase A DNA polymerase is a member of a family of enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into different molecules ...

s; here the holoenzyme is the complete complex containing all the subunits needed for activity.

## Coenzymes

Coenzymes are small organic molecules that can be loosely or tightly bound to an enzyme. Coenzymes transport chemical groups from one enzyme to another. Examples include
NADH Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate ...
,
NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle The Calvin cycle, light-independent reactions, bio syn ...
and
adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of organic compounds are known. The study of the properti ...

(ATP). Some coenzymes, such as
flavin mononucleotide Flavin mononucleotide (FMN), or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as the prosthetic group of various oxidoreductases, including NADH dehydrogenase, as ...

(FMN),
flavin adenine dinucleotide In biochemistry Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biolo ...

thiamine pyrophosphate Thiamine pyrophosphate (TPP or ThPP), or thiamine diphosphate (ThDP), or cocarboxylase is a thiamine (vitamin B1) Derivative (chemistry), derivative which is produced by the enzyme thiamine diphosphokinase. Thiamine pyrophosphate is a cofactor (bi ...

(TPP), and (THF), are derived from
vitamin A vitamin is an organic molecule , CH4; is among the simplest organic compounds. In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen chemical bond, bonds. Due to carbon's ability to Catenation, ...
s. These coenzymes cannot be synthesized by the body ''
de novo In general usage, ''de novo'' (literally 'of new') is Latin expression used in English to mean 'from the beginning', 'anew'. De novo may also refer to: Biology * ''De novo'', mutation, an alteration in a gene that is present for the first time in ...
'' and closely related compounds (vitamins) must be acquired from the diet. The chemical groups carried include: * the
hydride In chemistry, a hydride is formally the anion of hydrogen, H−. The term is applied loosely. At one extreme, all chemical compound, compounds containing covalent bond, covalently bound H atoms are called hydrides: water (H2O) is a hydride of o ...

ion (H), carried by NAD or NADP+ * the phosphate group, carried by
adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of organic compounds are known. The study of the properti ...

* the acetyl group, carried by
coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the Fatty acid metabolism#Synthesis, synthesis and Fatty acid metabolism#.CE.B2-Oxidation, oxidation of fatty acids, and the oxidation of pyruvic acid, pyruvate in the citric aci ...
* formyl, methenyl or methyl groups, carried by
folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins B vitamins are a class of water-soluble vitamin A vitamin is an organic molecule , CH4; is among the simplest organic compounds. In chemistry, organic compounds ar ...

and * the methyl group, carried by
S-adenosylmethionine ''S''-Adenosyl methionine (SAM-e) is a common cofactor (biochemistry), cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throughout the body, most SAM-e is produced and ...

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 1000 enzymes are known to use the coenzyme NADH. Coenzymes are usually continuously regenerated and their concentrations maintained at a steady level inside the cell. For example, NADPH is regenerated through the
pentose phosphate pathway In chemistry, a pentose is a monosaccharide (simple sugar) with five carbon atom, atoms. The chemical formula of all pentoses is , and their molecular weight is 150.13 g/mol.
methionine adenosyltransferase S-adenosylmethionine synthetase () (also known as methionine adenosyltransferase (MAT)) is an enzyme that Catalysis, creates S-Adenosyl methionine, S-adenosylmethionine (a.k.a. AdoMet, SAM or SAMe) by reacting methionine (a non-polar amino acid) and ...
. This continuous regeneration means that small amounts of coenzymes can be used very intensively. For example, the human body turns over its own weight in ATP each day.

# Thermodynamics

As with all catalysts, enzymes do not alter the position of the chemical equilibrium of the reaction. In the presence of an enzyme, the reaction runs in the same direction as it would without the enzyme, just more quickly. For example,
carbonic anhydrase The carbonic anhydrases (or carbonate dehydratases) form a family of enzymes that catalyst, catalyze the interconversion between carbon dioxide and water and the Dissociation (chemistry), dissociated ions of carbonic acid (i.e. bicarbonate and ...

catalyzes its reaction in either direction depending on the concentration of its reactants: The rate of a reaction is dependent on the
activation energy In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they undergo during ...

needed to form the
transition state The transition state of a chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substance A chemical substance is a form of matter In classical physics and general chemistr ...

which then decays into products. Enzymes increase reaction rates by lowering the energy of the transition state. First, binding forms a low energy enzyme-substrate complex (ES). Second, the enzyme stabilises the transition state such that it requires less energy to achieve compared to the uncatalyzed reaction (ES). Finally the enzyme-product complex (EP) dissociates to release the products. Enzymes can couple two or more reactions, so that a thermodynamically favorable reaction can be used to "drive" a thermodynamically unfavourable one so that the combined energy of the products is lower than the substrates. For example, the hydrolysis of
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armenia Tree Project * Association for Transpersonal Psychology * ATP architects engineers office * ATP ...

is often used to drive other chemical reactions.

# Kinetics

Enzyme kinetics is the investigation of how enzymes bind substrates and turn them into products. The rate data used in kinetic analyses are commonly obtained from
enzyme assay Enzyme assays are laboratory methods for measuring enzyme, enzymatic activity. They are vital for the study of enzyme kinetics and enzyme inhibitor, enzyme inhibition. Enzyme units The quantity or concentration of an enzyme can be expressed in Mol ...
s. In 1913
Leonor Michaelis Leonor Michaelis (January 16, 1875 – October 8, 1949) was a German biochemist, physical chemist, and physician A physician (American English), medical practitioner (English in the Commonwealth of Nations, Commonwealth English), medica ...

and Maud Leonora Menten proposed a quantitative theory of enzyme kinetics, which is referred to as
Michaelis–Menten kinetics upright=1.3, Michaelis–Menten saturation curve for an enzyme reaction showing the relation between the substrate concentration and reaction rate. In biochemistry Biochemistry or biological chemistry, is the study of chemical processes within ...
. The major contribution of Michaelis and Menten was to think of enzyme reactions in two stages. In the first, the substrate binds reversibly to the enzyme, forming the enzyme-substrate complex. This is sometimes called the Michaelis–Menten complex in their honor. The enzyme then catalyzes the chemical step in the reaction and releases the product. This work was further developed by G. E. Briggs and , who derived kinetic equations that are still widely used today. Enzyme rates depend on
solution Solution may refer to: * Solution (chemistry) Image:SaltInWaterSolutionLiquid.jpg, upMaking a saline water solution by dissolving Salt, table salt (sodium chloride, NaCl) in water. The salt is the solute and the water the solvent. In chemistry ...
conditions and substrate
concentration In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in t ...

. 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 complex. At the maximum reaction rate (''V''max) 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. ''V''max is only one of several important kinetic parameters. The amount of substrate needed to achieve a given rate of reaction is also important. This is given by the Michaelis–Menten constant (''K''m), which is the substrate concentration required for an enzyme to reach one-half its maximum reaction rate; generally, each enzyme has a characteristic ''K''M for a given substrate. Another useful constant is ''k''cat, also called the ''turnover number'', which is the number of substrate molecules handled by one active site per second. The efficiency of an enzyme can be expressed in terms of ''k''cat/''K''m. This is also called the specificity constant and incorporates the
rate constantIn chemical kinetics a reaction rate constant or reaction rate coefficient, ''k'', quantifies the rate and direction of a chemical reaction. For a reaction between reactants A and B to form product C :''a'' A + ''b'' B → ''c'' C th ...
s for all steps in the reaction up to and including the first irreversible step. Because the specificity constant reflects both affinity and catalytic ability, it is useful for comparing different enzymes against each other, or the same enzyme with different substrates. The theoretical maximum for the specificity constant is called the diffusion limit and is about 108 to 109 (M−1 s−1). At this point every collision of the enzyme with its substrate will result in catalysis, and the rate of product formation is not limited by the reaction rate but by the diffusion rate. Enzymes with this property are called '' catalytically perfect'' or ''kinetically perfect''. Example of such enzymes are triosephosphateisomerase, triose-phosphate isomerase,
carbonic anhydrase The carbonic anhydrases (or carbonate dehydratases) form a family of enzymes that catalyst, catalyze the interconversion between carbon dioxide and water and the Dissociation (chemistry), dissociated ions of carbonic acid (i.e. bicarbonate and ...

, acetylcholinesterase,
catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyst, catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in prote ...

, fumarase, β-lactamase, and superoxide dismutase. The turnover of such enzymes can reach several million reactions per second. But most enzymes are far from perfect: the average values of $k_/K_$ and $k_$ are about $10^5 ^^$ and $10 ^$, respectively. Michaelis–Menten kinetics relies on the law of mass action, which is derived from the assumptions of free diffusion and thermodynamically driven random collision. Many biochemical or cellular processes deviate significantly from these conditions, because of macromolecular crowding and constrained molecular movement. More recent, complex extensions of the model attempt to correct for these effects.

# Inhibition

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

## Types of inhibition

### Competitive

A competitive inhibitor and substrate cannot bind to the enzyme at the same time. Often competitive inhibitors strongly resemble the real substrate of the enzyme. For example, the drug methotrexate is a competitive inhibitor of the enzyme
dihydrofolate reductase Dihydrofolate reductase, or DHFR, is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), sub ...
, which catalyzes the reduction of folic acid, dihydrofolate to tetrahydrofolate. The similarity between the structures of dihydrofolate and this drug are shown in the accompanying figure. This type of inhibition can be overcome with high substrate concentration. In some cases, the inhibitor can bind to a site other than the binding-site of the usual substrate and exert an #Allosteric modulation, allosteric effect to change the shape of the usual binding-site.

### Non-competitive

A non-competitive inhibition, non-competitive inhibitor binds to a site other than where the substrate binds. The substrate still binds with its usual affinity and hence Km remains the same. However the inhibitor reduces the catalytic efficiency of the enzyme so that Vmax is reduced. In contrast to competitive inhibition, non-competitive inhibition cannot be overcome with high substrate concentration.

### Uncompetitive

An uncompetitive inhibitor cannot bind to the free enzyme, only to the enzyme-substrate complex; hence, these types of inhibitors are most effective at high substrate concentration. In the presence of the inhibitor, the enzyme-substrate complex is inactive. This type of inhibition is rare.

### Mixed

A mixed inhibition, mixed inhibitor binds to an allosteric site and the binding of the substrate and the inhibitor affect each other. The enzyme's function is reduced but not eliminated when bound to the inhibitor. This type of inhibitor does not follow the Michaelis–Menten equation.

### Irreversible

An irreversible inhibitor permanently inactivates the enzyme, usually by forming a
covalent bond A covalent bond is a chemical bond that involves the sharing of electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs, and the stable balance of attractive and repulsive forces between atoms, when they s ...
to the protein. Penicillin and aspirin are common drugs that act in this manner.

## Functions of inhibitors

In many organisms, inhibitors may act as part of a
feedback Feedback occurs when outputs of a system are routed back as inputs as part of a chain A chain is a assembly of connected pieces, called links, typically made of metal, with an overall character similar to that of a in that it is flexib ...

mechanism. If an enzyme produces too much of one substance in the organism, that substance may act as an inhibitor for the enzyme at the beginning of the pathway that produces it, causing production of the substance to slow down or stop when there is sufficient amount. This is a form of negative feedback. Major metabolic pathways such as the citric acid cycle make use of this mechanism. Since inhibitors modulate the function of enzymes they are often used as drugs. Many such drugs are reversible competitive inhibitors that resemble the enzyme's native substrate, similar to methotrexate above; other well-known examples include statins used to treat high cholesterol, and protease inhibitor (pharmacology), protease inhibitors used to treat retrovirus, retroviral infections such as HIV. A common example of an irreversible inhibitor that is used as a drug is aspirin, which inhibits the Cyclooxygenase, COX-1 and Cyclooxygenase, COX-2 enzymes that produce the inflammation messenger prostaglandin. Other enzyme inhibitors are poisons. For example, the poison cyanide is an irreversible enzyme inhibitor that combines with the copper and iron in the active site of the enzyme cytochrome c oxidase and blocks cellular respiration.

# Factors affecting enzyme activity

As enzymes are made up of proteins, their actions are sensitive to change in many physio chemical factors such as pH, temperature, substrate concentration, etc. The following table shows pH optima for various enzymes.

# Biological function

Enzymes serve a wide variety of function (biology), functions inside living organisms. They are indispensable for signal transduction and cell regulation, often via kinases and phosphatases. They also generate movement, with myosin hydrolyzing ATP to generate muscle contraction, and also transport cargo around the cell as part of the cytoskeleton. Other ATPases in the cell membrane are ion pump (biology), ion pumps involved in active transport. Enzymes are also involved in more exotic functions, such as luciferase generating light in firefly, fireflies. Viruses can also contain enzymes for infecting cells, such as the HIV integrase and reverse transcriptase, or for viral release from cells, like the influenza virus neuraminidase. An important function of enzymes is in the digestive systems of animals. Enzymes such as amylases and
protease A protease (also called a peptidase or proteinase) is an enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into differe ...

s break down large molecules (
starch Starch or amylum is a polymeric A polymer (; Greek '' poly-'', "many" + '' -mer'', "part") is a substance Substance may refer to: * Substance (Jainism), a term in Jain ontology to denote the base or owner of attributes * Chemical substance ...
or
protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...

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 hydrolyze the starch chains into smaller molecules such as maltose and eventually glucose, which can then be absorbed. Different enzymes digest different food substances. In ruminants, which have Herbivore, herbivorous diets, microorganisms in the gut produce another enzyme, cellulase, to break down the cellulose cell walls of plant fiber.

## Metabolism

Several enzymes can work together in a specific order, creating metabolic pathways. In a metabolic pathway, one enzyme takes the product of another enzyme as a substrate. After the catalytic reaction, the product is then passed on to another enzyme. Sometimes more than one enzyme can catalyze the same reaction in parallel; this can allow more complex regulation: with, for example, a low constant activity 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 and could not be regulated to serve the needs of the cell. Most central metabolic pathways are regulated at a few key steps, typically through enzymes whose activity involves the hydrolysis of
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armenia Tree Project * Association for Transpersonal Psychology * ATP architects engineers office * ATP ...

. Because this reaction releases so much energy, other reactions that are endothermic, thermodynamically unfavorable can be coupled to ATP hydrolysis, driving the overall series of linked metabolic reactions.

## Control of activity

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

### Regulation

Enzymes can be either enzyme activator, activated or enzyme inhibitor, inhibited by other molecules. 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, negative feedback mechanism, because the amount of the end product produced is regulated by its own concentration. Negative feedback mechanism can effectively adjust the rate of synthesis of intermediate metabolites according to the demands of the cells. This helps with effective allocations of materials and energy economy, and it prevents the excess manufacture of end products. Like other homeostasis, homeostatic devices, the control of enzymatic action helps to maintain a stable internal environment in living organisms.

### Post-translational modification

Examples of post-translational modification include phosphorylation, myristoylation and glycosylation. For example, in the response to insulin, the phosphorylation of multiple enzymes, including glycogen synthase, helps control the synthesis or degradation of glycogen and allows the cell to respond to changes in blood sugar. Another example of post-translational modification is the cleavage of the polypeptide chain. Chymotrypsin, a digestive
protease A protease (also called a peptidase or proteinase) is an enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into differe ...

, is produced in inactive form as chymotrypsinogen in the pancreas and transported in this form to the stomach where it is activated. This stops the enzyme from digesting the pancreas or other tissues before it enters the gut. This type of inactive precursor to an enzyme is known as a zymogen or proenzyme.

### Quantity

Enzyme production (Transcription (genetics), transcription and Translation (genetics), translation of enzyme genes) can be enhanced or diminished by a cell in response to changes in the cell's environment. This form of regulation of gene expression, gene regulation is called enzyme induction. For example, bacteria may become antibiotic resistance, resistant to antibiotics such as penicillin because enzymes called beta-lactamases are induced that hydrolyse the crucial Beta-lactam, beta-lactam ring within the penicillin molecule. Another example comes from enzymes in the liver called cytochrome P450 oxidases, which are important in drug metabolism. Induction or inhibition of these enzymes can cause drug interactions. Enzyme levels can also be regulated by changing the rate of enzyme catabolism, degradation. The opposite of enzyme induction is enzyme repression.

### Subcellular distribution

Enzymes can be compartmentalized, with different metabolic pathways occurring in different cellular compartments. For example, fatty acids are synthesized by one set of enzymes in the cytosol, endoplasmic reticulum and golgi apparatus, Golgi and used by a different set of enzymes as a source of energy in the mitochondrion, through β-oxidation. In addition, protein targeting, trafficking of the enzyme to different compartments may change the degree of protonation (e.g., the neutral cytoplasm and the acidic lysosome) or oxidative state (e.g., oxidizing periplasm or reducing cytoplasm) which in turn affects enzyme activity. In contrast to partitioning into membrane bound organelles, enzyme subcellular localisation may also be altered through polymerisation of enzymes into macromolecular cytoplasmic filaments.

### Organ specialization

In multicellular eukaryotes, cells in different organ (anatomy), organs and tissue (biology), tissues have different patterns of gene expression and therefore have different sets of enzymes (known as isozymes) available for metabolic reactions. This provides a mechanism for regulating the overall metabolism of the organism. For example,
hexokinase A hexokinase is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the e ...
, the first enzyme in the glycolysis pathway, has a specialized form called glucokinase expressed in the liver and pancreas that has a lower affinity (pharmacology), affinity for glucose yet is more sensitive to glucose concentration. This enzyme is involved in sensing blood sugar and regulating insulin production.

## Involvement in disease

Since the tight control of enzyme activity is essential for homeostasis, any malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a genetic disease. The malfunction of just one type of enzyme out of the thousands of types present in the human body can be fatal. An example of a fatal genetic disease due to enzyme insufficiency is Tay–Sachs disease, in which patients lack the enzyme hexosaminidase. One example of enzyme deficiency is the most common type of phenylketonuria. Many different single amino acid mutations in the enzyme phenylalanine hydroxylase, which catalyzes the first step in the degradation of phenylalanine, result in build-up of phenylalanine and related products. Some mutations are in the active site, directly disrupting binding and catalysis, but many are far from the active site and reduce activity by destabilising the protein structure, or affecting correct oligomerisation. This can lead to intellectual disability if the disease is untreated. Another example is pseudocholinesterase deficiency, in which the body's ability to break down choline ester drugs is impaired. Oral administration of enzymes can be used to treat some functional enzyme deficiencies, such as pancreatic insufficiency and lactose intolerance. Another way enzyme malfunctions can cause disease comes from germline mutations in genes coding for DNA repair enzymes. Defects in these enzymes cause cancer because cells are less able to repair mutations in their
genome In the fields of molecular biology Molecular biology is the branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, M ...

s. This causes a slow accumulation of mutations and results in the carcinogenesis, development of cancers. An example of such a hereditary cancer syndrome is xeroderma pigmentosum, which causes the development of skin cancers in response to even minimal exposure to ultraviolet light.

# Evolution

Similar to any other protein, enzymes change over time through mutations and sequence divergence. Given their central role in metabolism, enzyme evolution plays a critical role in adaptation. A key question is therefore whether and how enzymes can change their enzymatic activities alongside. It is generally accepted that many new enzyme activities have evolved through gene duplication and mutation of the duplicate copies although evolution can also happen without duplication. One example of an enzyme that has changed its activity is the ancestor of Methionyl aminopeptidase, methionyl amino peptidase (MAP) and creatine amidinohydrolase (creatinase) which are clearly homologous but catalyze very different reactions (MAP removes the amino-terminal methionine in new proteins while creatinase hydrolyses creatine to sarcosine and urea). In addition, MAP is metal-ion dependent while creatinase is not, hence this property was also lost over time. Small changes of enzymatic activity are extremely common among enzymes. In particular, substrate binding specificity (see above) can easily and quickly change with single amino acid changes in their substrate binding pockets. This is frequently seen in the main enzyme classes such as kinases. Artificial (in vitro) evolution is now commonly used to modify enzyme activity or specificity for industrial applications (see below).

# Industrial applications

Enzymes are used in the chemical industry and other industrial applications when extremely specific catalysts are required. Enzymes in general are limited in the number of reactions they have evolved to catalyze and also by their lack of stability in organic solvents and at high temperatures. As a consequence, protein engineering is an active area of research and involves attempts to create new enzymes with novel properties, either through rational design or ''in vitro'' evolution. These efforts have begun to be successful, and a few enzymes have now been designed "from scratch" to catalyze reactions that do not occur in nature.

* Industrial enzymes * List of enzymes * Molecular machine

## Enzyme databases

* BRENDA * ExPASy * IntEnz * KEGG * MetaCyc

# References

## General

* , A biochemistry textbook available free online through NCBI Bookshelf.

## Etymology and history

*, A history of early enzymology.

*

## Kinetics and inhibition

* {{Authority control Enzymes, Biomolecules Catalysis Metabolism Process chemicals