Enzyme synthesis of antibiotics.

In addition, some
household products use enzymes to speed
up biochemical reactions (e.g., enzymes in
Human glyoxalase I. Two zinc ions that are biological washing powders break down
needed for the enzyme to catalyze its protein or fat stains on clothes; enzymes in
reaction are shown as purple spheres, and meat tenderizers break down proteins,
an enzyme inhibitor called S- making the meat easier to chew).
hexylglutathione is shown as a space-filling
model, filling the two active sites. Etymology and history

Enzymes are proteins that catalyze (i.e.,

increase the rates of) chemical reactions.[1][2]
In enzymatic reactions, the molecules at the
beginning of the process are called
substrates, and the enzyme converts them
into different molecules, called the
products. Almost all processes in a
biological cell 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 pathways
occur in that cell.
Eduard Buchner
Like all catalysts, enzymes work by lowering
the activation energy (Ea‡) for a reaction, As early as the late 1700s and early 1800s,
thus dramatically increasing the rate of the the digestion of meat by stomach
reaction. Most enzyme reaction rates are secretions[7] and the conversion of starch to
millions of times faster than those of sugars by plant extracts and saliva were
comparable un-catalyzed reactions. As with known. However, the mechanism by which
all catalysts, enzymes are not consumed by this occurred had not been identified.[8]
the reactions they catalyze, nor do they
alter the equilibrium of these reactions. In the 19th century, when studying the
However, enzymes do differ from most fermentation of sugar to alcohol by yeast,
other catalysts by being much more Louis Pasteur came to the conclusion that
specific. Enzymes are known to catalyze this fermentation was catalyzed by a vital
about 4,000 biochemical reactions.[3] A few force contained within the yeast cells called
RNA molecules called ribozymes also "ferments", which were thought to function
catalyze reactions, with an important only within living organisms. He wrote that
example being some parts of the ribosome. "alcoholic fermentation is an act correlated
[4][5]
Synthetic molecules called artificial with the life and organization of the yeast
enzymes also display enzyme-like catalysis. cells, not with the death or putrefaction of
[6] the cells."[9]

Enzyme activity can be affected by other In 1877, German physiologist Wilhelm

molecules. Inhibitors are molecules that Kühne (1837–1900) first used the term
decrease enzyme activity; activators are enzyme, which comes from Greek ενζυμον,
molecules that increase activity. Many "in leaven", to describe this process. [10] The
drugs and poisons are enzyme inhibitors. word enzyme was used later to refer to
Activity is also affected by temperature, nonliving substances such as pepsin, and
chemical environment (e.g., pH), and the the word ferment was used to refer to
concentration of substrate. Some enzymes chemical activity produced by living
are used commercially, for example, in the organisms.
In 1897, Eduard Buchner began to study the effort to understand how enzymes work at
ability of yeast extracts that lacked any an atomic level of detail.
living yeast cells to ferment sugar. In a
series of experiments at the University of Structures and mechanisms
Berlin, he found that the sugar was
fermented even when there were no living See also: Enzyme catalysis
yeast cells in the mixture. [11] He named the
enzyme that brought about the
[12]
fermentation of sucrose "zymase". In
1907, he received the Nobel Prize in
Chemistry "for his biochemical research and
his discovery of cell-free fermentation".
Following Buchner's example, enzymes are
usually named according to the reaction
they carry out. Typically, to generate the
name of an enzyme, the suffix -ase is added
to the name of its substrate (e.g., lactase is
the enzyme that cleaves lactose) or the type
of reaction (e.g., DNA polymerase forms
DNA polymers).[13]

Having shown that enzymes could function Ribbon diagram showing carbonic
outside a living cell, the next step was to anhydrase II. The grey sphere is the zinc
determine their biochemical nature. Many cofactor in the active site. Diagram drawn
early workers noted that enzymatic activity from PDB 1MOO.
was associated with proteins, but several
scientists (such as Nobel laureate Richard Enzymes are generally globular proteins and
Willstätter) argued that proteins were range from just 62 amino acid residues in
merely carriers for the true enzymes and size, for the monomer of 4-oxalocrotonate
that proteins per se were incapable of tautomerase,[16] to over 2,500 residues in
catalysis. However, in 1926, James B. the animal fatty acid synthase.[17] A small
Sumner showed that the enzyme urease number of RNA-based biological catalysts
was a pure protein and crystallized it; exist, with the most common being the
Sumner did likewise for the enzyme ribosome; these are referred to as either
catalase in 1937. The conclusion that pure RNA-enzymes or ribozymes. The activities of
proteins can be enzymes was definitively enzymes are determined by their three-
proved by Northrop and Stanley, who dimensional structure.[18] However,
worked on the digestive enzymes pepsin although structure does determine
(1930), trypsin and chymotrypsin. These function, predicting a novel enzyme's
three scientists were awarded the 1946 activity just from its structure is a very
Nobel Prize in Chemistry.[14] difficult problem that has not yet been
solved.[19]
This discovery that enzymes could be
crystallized eventually allowed their Most enzymes are much larger than the
structures to be solved by x-ray substrates they act on, and only a small
crystallography. This was first done for portion of the enzyme (around 3–4 amino
lysozyme, an enzyme found in tears, saliva acids) is directly involved in catalysis. [20] The
and egg whites that digests the coating of region that contains these catalytic
some bacteria; the structure was solved by residues, binds the substrate, and then
a group led by David Chilton Phillips and carries out the reaction is known as the
published in 1965.[15] This high-resolution active site. Enzymes can also contain sites
structure of lysozyme marked the beginning that bind cofactors, which are needed for
of the field of structural biology and the catalysis. Some enzymes also have binding
sites for small molecules, which are often Some enzymes that produce secondary
direct or indirect products or substrates of metabolites are described as promiscuous,
the reaction catalyzed. This binding can as they can act on a relatively broad range
serve to increase or decrease the enzyme's of different substrates. It has been
activity, providing a means for feedback suggested that this broad substrate
regulation. specificity is important for the evolution of
new biosynthetic pathways.[27]
Like all proteins, enzymes are comprised of
long, linear chains of amino acids that fold [edit] "Lock and key" model
to produce a three-dimensional product.
Each unique amino acid sequence produces Enzymes are very specific, and it was
a specific structure, which has unique suggested by Emil Fischer in 1894 that this
properties. Individual protein chains may was because both the enzyme and the
sometimes group together to form a substrate possess specific complementary
protein complex. Most enzymes can be geometric shapes that fit exactly into one
denatured—that is, unfolded and another.[28] This is often referred to as "the
inactivated—by heating or chemical lock and key" model. However, while this
denaturants, which disrupt the three- model explains enzyme specificity, it fails to
dimensional structure of the protein. explain the stabilization of the transition
Depending on the enzyme, denaturation state that enzymes achieve. The "lock and
may be reversible or irreversible. key" model is therefore less accurate than
the induced fit model.
Structures of enzymes in complex with
substrates or substrate analogs during a Induced fit model
reaction may be obtained using Time
resolved crystallography methods.

[edit] Specificity

Enzymes are usually very specific as to

which reactions they catalyze and the
substrates that are involved in these
reactions. Complementary shape, charge
and hydrophilic/hydrophobic characteristics
of enzymes and substrates are responsible
for this specificity. Enzymes can also show
impressive levels of stereospecificity,
regioselectivity and chemoselectivity.[21]

Some of the enzymes showing the highest

specificity and accuracy are involved in the
copying and expression of the genome.
These enzymes have "proof-reading"
mechanisms. Here, an enzyme such as DNA Diagrams to show the induced fit
polymerase catalyzes a reaction in a first hypothesis of enzyme action.
step and then checks that the product is
correct in a second step.[22] This two-step In 1958, Daniel Koshland suggested a
process results in average error rates of less modification to the lock and key model:
than 1 error in 100 million reactions in high- since enzymes are rather flexible structures,
fidelity mammalian polymerases.[23] Similar the active site is continually reshaped by
proofreading mechanisms are also found in interactions with the substrate as the
RNA polymerase,[24] aminoacyl tRNA substrate interacts with the enzyme.[29] As a
synthetases[25] and ribosomes.[26] result, the substrate does not simply bind to
a rigid active site; the amino acid side
chains which make up the active site are enzymes like thermolabile enzymes
molded into the precise positions that work best at low temperatures.
enable the enzyme to perform its catalytic
function. In some cases, such as Interestingly, this entropic effect involves
glycosidases, the substrate molecule also destabilization of the ground state,[33] and
changes shape slightly as it enters the active its contribution to catalysis is relatively
site.[30] The active site continues to change small.[34]
until the substrate is completely bound, at
which point the final shape and charge is Transition State Stabilization
determined.[31]
The understanding of the origin of the
Mechanisms reduction of ΔG‡ requires one to find out
how the enzymes can stabilize its transition
Enzymes can act in several ways, all of state more than the transition state of the
which lower ΔG‡:[32] uncatalyzed reaction. Apparently, the most
effective way for reaching large stabilization
 Lowering the activation energy by is the use of electrostatic effects, in
creating an environment in which particular, by having a relatively fixed polar
the transition state is stabilized (e.g. environment that is oriented toward the
straining the shape of a substrate— charge distribution of the transition state. [35]
by binding the transition-state Such an environment does not exist in the
conformation of the uncatalyzed reaction in water.
substrate/product molecules, the
enzyme distorts the bound Dynamics and function
substrate(s) into their transition
state form, thereby reducing the See also: Protein dynamics
amount of energy required to
complete the transition). The internal dynamics of enzymes is linked
 Lowering the energy of the to their mechanism of catalysis. [36][37][38]
transition state, but without Internal dynamics are the movement of
distorting the substrate, by creating parts of the enzyme's structure, such as
an environment with the opposite individual amino acid residues, a group of
charge distribution to that of the amino acids, or even an entire protein
transition state. domain. These movements occur at various
 Providing an alternative pathway. time-scales ranging from femtoseconds to
For example, temporarily reacting seconds. Networks of protein residues
with the substrate to form an throughout an enzyme's structure can
intermediate ES complex, which contribute to catalysis through dynamic
would be impossible in the absence motions.[39][40][41][42] Protein motions are vital
of the enzyme. to many enzymes, but whether small and
 Reducing the reaction entropy fast vibrations, or larger and slower
change by bringing substrates conformational movements are more
together in the correct orientation important depends on the type of reaction
to react. Considering ΔH‡ alone involved. However, although these
overlooks this effect. movements are important in binding and
 Increases in temperatures speed up releasing substrates and products, it is not
reactions. Thus, temperature clear if protein movements help to
increases help the enzyme function accelerate the chemical steps in enzymatic
and develop the end product even reactions.[43] These new insights also have
faster. However, if heated too much, implications in understanding allosteric
the enzyme’s shape deteriorates effects and developing new drugs.
and only when the temperature
comes back to normal does the
enzyme regain its shape. Some
Allosteric modulation usually found in the active site and are
involved in catalysis. For example, flavin
and heme cofactors are often involved in
redox reactions.

Enzymes that require a cofactor but do not

have one bound are called apoenzymes or
apoproteins. An apoenzyme together with
its cofactor(s) is called a holoenzyme (this is
Allosteric transition of an enzyme between the active form). Most cofactors are not
R and T states, stabilised by an agonist, an covalently attached to an enzyme, but are
inhibitor and a substrate (the MWC model) very tightly bound. However, organic
Main article: Allosteric regulation prosthetic groups can be covalently bound
(e.g., thiamine pyrophosphate in the
Allosteric sites are sites on the enzyme that enzyme pyruvate dehydrogenase). The term
bind to molecules in the cellular "holoenzyme" can also be applied to
environment. The sites form weak, enzymes that contain multiple protein
noncovalent bonds with these molecules, subunits, such as the DNA polymerases;
causing a change in the conformation of the here the holoenzyme is the complete
enzyme. This change in conformation complex containing all the subunits needed
translates to the active site, which then for activity.
affects the reaction rate of the enzyme. [44]
Allosteric interactions can both inhibit and Coenzymes
activate enzymes and are a common way
that enzymes are controlled in the body.[45]

Cofactors and coenzymes

Main articles: Cofactor (biochemistry) and

Coenzyme

Cofactors

Some enzymes do not need any additional

Space-filling model of the coenzyme NADH
components to show full activity. However,
others require non-protein molecules called Coenzymes are small organic molecules that
cofactors to be bound for activity. [46] transport chemical groups from one
Cofactors can be either inorganic (e.g., enzyme to another.[49] Some of these
metal ions and iron-sulfur clusters) or chemicals such as riboflavin, thiamine and
organic compounds (e.g., flavin and heme). folic acid are vitamins (compounds which
Organic cofactors can be either prosthetic cannot be synthesized by the body and
groups, which are tightly bound to an must be acquired from the diet). The
enzyme, or coenzymes, which are released chemical groups carried include the hydride
from the enzyme's active site during the ion (H-) carried by NAD or NADP+, the phosphate
reaction. Coenzymes include NADH, NADPH group carried by adenosine triphosphate,
and adenosine triphosphate. These the acetyl group carried by coenzyme A,
molecules transfer chemical groups formyl, methenyl or methyl groups carried
between enzymes.[47] by folic acid and the methyl group carried
by S-adenosylmethionine.
An example of an enzyme that contains a
cofactor is carbonic anhydrase, and is Since coenzymes are chemically changed as
shown in the ribbon diagram above with a a consequence of enzyme action, it is useful
zinc cofactor bound as part of its active site. to consider coenzymes to be a special class
[48]
These tightly bound molecules are
of substrates, or second substrates, which Furthermore, enzymes can couple two or
are common to many different enzymes. more reactions, so that a
For example, about 700 enzymes are known thermodynamically favorable reaction can
to use the coenzyme NADH.[50] be used to "drive" a thermodynamically
unfavorable one. For example, the
Coenzymes are usually continuously hydrolysis of ATP is often used to drive
regenerated and their concentrations other chemical reactions.[52]
maintained at a steady level inside the cell:
for example, NADPH is regenerated through Enzymes catalyze the forward and
the pentose phosphate pathway and S- backward reactions equally. They do not
adenosylmethionine by methionine alter the equilibrium itself, but only the
adenosyltransferase. This continuous speed at which it is reached. For example,
regeneration means that even small carbonic anhydrase catalyzes its reaction in
amounts of coenzymes are used very either direction depending on the
intensively. For example, the human body concentration of its reactants.
turns over its own weight in ATP each day.
[51]

(in tissues; high CO2 concentration)

Thermodynamics
(in lungs; low CO2 concentration)

Nevertheless, if the equilibrium is greatly

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

Kinetics

Main article: Enzyme kinetics

The energies of the stages of a chemical
reaction. Substrates need a lot of energy to
reach a transition state, which then decays
into products. The enzyme stabilizes the
transition state, reducing the energy
needed to form products.
Main articles: Activation energy,
Thermodynamic equilibrium, and Chemical Mechanism for a single substrate enzyme
equilibrium catalyzed reaction. The enzyme (E) binds a
substrate (S) and produces a product (P).
As all catalysts, enzymes do not alter the
position of the chemical equilibrium of the Enzyme kinetics is the investigation of how
reaction. Usually, in the presence of an enzymes bind substrates and turn them into
enzyme, the reaction runs in the same products. The rate data used in kinetic
direction as it would without the enzyme, analyses are obtained from enzyme assays.
just more quickly. However, in the absence
of the enzyme, other possible uncatalyzed, In 1902 Victor Henri[53] proposed a
"spontaneous" reactions might lead to quantitative theory of enzyme kinetics, but
different products, because in those his experimental data were not useful
conditions this different product is formed because the significance of the hydrogen
faster. ion concentration was not yet appreciated.
After Peter Lauritz Sørensen had defined increased until a constant rate of product
the logarithmic pH-scale and introduced the formation is seen. This is shown in the
concept of buffering in 1909[54] the German saturation curve on the right. Saturation
chemist Leonor Michaelis and his Canadian happens because, as substrate
postdoc Maud Leonora Menten repeated concentration increases, more and more of
Henri's experiments and confirmed his the free enzyme is converted into the
equation which is referred to as Henri- substrate-bound ES form. At the maximum
Michaelis-Menten kinetics (sometimes also velocity (Vmax) of the enzyme, all the enzyme
Michaelis-Menten kinetics).[55] Their work active sites are bound to substrate, and the
was further developed by G. E. Briggs and J. amount of ES complex is the same as the
B. S. Haldane, who derived kinetic total amount of enzyme. However, Vmax is
equations that are still widely used today.[56] only one kinetic constant of enzymes. The
amount of substrate needed to achieve a
The major contribution of Henri was to given rate of reaction is also important. This
think of enzyme reactions in two stages. In is given by the Michaelis-Menten constant
the first, the substrate binds reversibly to (Km), which is the substrate concentration
the enzyme, forming the enzyme-substrate required for an enzyme to reach one-half its
complex. This is sometimes called the maximum velocity. Each enzyme has a
Michaelis complex. The enzyme then characteristic Km for a given substrate, and
catalyzes the chemical step in the reaction this can show how tight the binding of the
and releases the product. 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
Saturation curve for an enzyme reaction theoretical maximum for the specificity
showing the relation between the substrate constant is called the diffusion limit and is
concentration (S) and rate (v). about 108 to 109 (M−1 s−1). At this point every
collision of the enzyme with its substrate
Enzymes can catalyze up to several million
will result in catalysis, and the rate of
reactions per second. For example, the
product formation is not limited by the
uncatalyzed decarboxylation of orotidine 5'-
reaction rate but by the diffusion rate.
monophosphate has a half life of 78 million
Enzymes with this property are called
years. However, when the enzyme orotidine
catalytically perfect or kinetically perfect.
5'-phosphate decarboxylase is added, the
Example of such enzymes are triose-
same process takes just 25 milliseconds. [57]
phosphate isomerase, carbonic anhydrase,
Enzyme rates depend on solution
acetylcholinesterase, catalase, fumarase, β-
conditions and substrate concentration.
lactamase, and superoxide dismutase.
Conditions that denature the protein
abolish enzyme activity, such as high Michaelis-Menten kinetics relies on the law
temperatures, extremes of pH or high salt of mass action, which is derived from the
concentrations, while raising substrate assumptions of free diffusion and
concentration tends to increase activity. To thermodynamically driven random collision.
find the maximum speed of an enzymatic However, many biochemical or cellular
reaction, the substrate concentration is processes deviate significantly from these
conditions, because of macromolecular Substrate and inhibitor compete for the
crowding, phase-separation of the enzyme.
enzyme/substrate/product, or one or two-
dimensional molecular movement.[58] In
these situations, a fractal Michaelis-Menten
kinetics may be applied.[59][60][61][62]

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.[63]
[64]
Quantum tunneling for protons has been
observed in tryptamine.[65] 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
Types of inhibition. This classification was
introduced by W.W. Cleland.[66]
Main article: Enzyme inhibitor

Enzyme reaction rates can be decreased by

various types of enzyme inhibitors.

Competitive inhibition

In competitive inhibition, the inhibitor and

substrate compete for the enzyme (i.e.,
they can not bind at the same time). [67]
Often competitive inhibitors strongly
resemble the real substrate of the enzyme.
For example, methotrexate is a competitive
inhibitor of the enzyme dihydrofolate
reductase, which catalyzes the reduction of
dihydrofolate to tetrahydrofolate. The
similarity between the structures of folic
acid and this drug are shown in the figure to
Competitive inhibitors bind reversibly to the the right bottom. Note that binding of the
enzyme, preventing the binding of inhibitor need not be to the substrate
substrate. On the other hand, binding of binding site (as frequently stated), if binding
substrate prevents binding of the inhibitor. 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 Km.

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 The coenzyme folic acid (left) and the anti-
multimeric enzymes. cancer drug methotrexate (right) are very
similar in structure. As a result,
Non-competitive inhibition methotrexate is a competitive inhibitor of
many enzymes that use folates.
Non-competitive inhibitors can bind to the
enzyme at the same time as the substrate, Irreversible inhibitors react with the
i.e. they never bind to the active site. Both enzyme and form a covalent adduct with
the EI and EIS complexes are enzymatically the protein. The inactivation is irreversible.
inactive. Because the inhibitor can not be These compounds include eflornithine a
driven from the enzyme by higher substrate drug used to treat the parasitic disease
concentration (in contrast to competitive sleeping sickness.[68] Penicillin and Aspirin
inhibition), the apparent Vmax changes. But also act in this manner. With these drugs,
because the substrate can still bind to the the compound is bound in the active site
enzyme, the Km stays the same. and the enzyme then converts the inhibitor
into an activated form that reacts
Mixed inhibition irreversibly with one or more amino acid
residues.
This type of inhibition resembles the non-
competitive, except that the EIS-complex Uses of inhibitors
has residual enzymatic activity.
Since inhibitors modulate the function of
In many organisms inhibitors may act as enzymes they are often used as drugs. An
part of a feedback mechanism. If an enzyme common example of an inhibitor that is
produces too much of one substance in the used as a drug is aspirin, which inhibits the
organism, that substance may act as an COX-1 and COX-2 enzymes that produce the
inhibitor for the enzyme at the beginning of inflammation messenger prostaglandin,
the pathway that produces it, causing thus suppressing pain and inflammation.
production of the substance to slow down However, other enzyme inhibitors are
or stop when there is sufficient amount. poisons. For example, the poison cyanide is
This is a form of negative feedback. an irreversible enzyme inhibitor that
Enzymes which are subject to this form of combines with the copper and iron in the
regulation are often multimeric and have active site of the enzyme cytochrome c
allosteric binding sites for regulatory oxidase and blocks cellular respiration.[69]
substances. Their substrate/velocity plots
are not hyperbolar, but sigmoidal (S- Biological function
shaped).
Enzymes serve a wide variety of functions
inside living organisms. They are
indispensable for signal transduction and
cell regulation, often via kinases and
phosphatases.[70] They also generate Glycolytic enzymes and their functions in
movement, with myosin hydrolysing ATP to the metabolic pathway of glycolysis
generate muscle contraction and also
moving cargo around the cell as part of the Several enzymes can work together in a
cytoskeleton.[71] Other ATPases in the cell specific order, creating metabolic pathways.
membrane are ion pumps involved in active In a metabolic pathway, one enzyme takes
transport. Enzymes are also involved in the product of another enzyme as a
more exotic functions, such as luciferase substrate. After the catalytic reaction, the
generating light in fireflies.[72] Viruses can product is then passed on to another
also contain enzymes for infecting cells, enzyme. Sometimes more than one enzyme
such as the HIV integrase and reverse can catalyze the same reaction in parallel,
transcriptase, or for viral release from cells, this can allow more complex regulation:
like the influenza virus neuraminidase. with for example a low constant activity
being provided by one enzyme but an
An important function of enzymes is in the inducible high activity from a second
digestive systems of animals. Enzymes such enzyme.
as amylases and proteases break down
large molecules (starch or proteins, Enzymes determine what steps occur in
respectively) into smaller ones, so they can these pathways. Without enzymes,
be absorbed by the intestines. Starch metabolism would neither progress through
molecules, for example, are too large to be the same steps, nor be fast enough to serve
absorbed from the intestine, but enzymes the needs of the cell. Indeed, a metabolic
hydrolyse the starch chains into smaller pathway such as glycolysis could not exist
molecules such as maltose and eventually independently of enzymes. Glucose, for
glucose, which can then be absorbed. example, can react directly with ATP to
Different enzymes digest different food become phosphorylated at one or more of
substances. In ruminants which have its carbons. In the absence of enzymes, this
herbivorous diets, microorganisms in the occurs so slowly as to be insignificant.
gut produce another enzyme, cellulase to However, if hexokinase is added, these slow
break down the cellulose cell walls of plant reactions continue to take place except that
fiber.[73] phosphorylation at carbon 6 occurs so
rapidly that if the mixture is tested a short
time later, glucose-6-phosphate is found to
be the only significant product.
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.

1. Enzyme production (transcription

and translation of enzyme genes)
can be enhanced or diminished by a
cell in response to changes in the
cell's environment. This form of
gene regulation is called enzyme
induction and inhibition (see
enzyme induction). For example,
bacteria may become resistant to
antibiotics such as penicillin because
enzymes called beta-lactamases are
 induced that hydrolyse the crucial or degradation of glycogen and
beta-lactam ring within the penicillin allows the cell to respond to
molecule. Another example are changes in blood sugar.[75] Another
enzymes in the liver called example of post-translational
cytochrome P450 oxidases, which modification is the cleavage of the
are important in drug metabolism. polypeptide chain. Chymotrypsin, a
Induction or inhibition of these digestive protease, is produced in
enzymes can cause drug inactive form as chymotrypsinogen
interactions. in the pancreas and transported in
2. Enzymes can be this form to the stomach where it is
compartmentalized, with different activated. This stops the enzyme
metabolic pathways occurring in from digesting the pancreas or other
different cellular compartments. For tissues before it enters the gut. This
example, fatty acids are synthesized type of inactive precursor to an
by one set of enzymes in the cytosol, enzyme is known as a zymogen.
endoplasmic reticulum and the Golgi 5. Some enzymes may become
apparatus and used by a different activated when localized to a
set of enzymes as a source of energy different environment (e.g. from a
in the mitochondrion, through β- reducing (cytoplasm) to an oxidising
oxidation.[74] (periplasm) environment, high pH to
3. Enzymes can be regulated by low pH etc.). For example,
inhibitors and activators. For hemagglutinin in the influenza virus
example, the end product(s) of a is activated by a conformational
metabolic pathway are often change caused by the acidic
inhibitors for one of the first conditions, these occur when it is
enzymes of the pathway (usually the taken up inside its host cell and
first irreversible step, called enters the lysosome.[76]
committed step), thus regulating the
amount of end product made by the Involvement in disease
pathways. Such a regulatory
mechanism is called a negative
feedback mechanism, because the
amount of the end product
produced is regulated by its own
concentration. Negative feedback
mechanism can effectively adjust
the rate of synthesis of intermediate
metabolites according to the
demands of the cells. This helps
allocate materials and energy
economically, and prevents the
manufacture of excess end
Phenylalanine hydroxylase. Created from
products. The control of enzymatic
PDB 1KW0
action helps to maintain a stable
internal environment in living
organisms.
4. Enzymes can be regulated through
post-translational modification. This
can include phosphorylation,
myristoylation and glycosylation. For
example, in the response to insulin,
the phosphorylation of multiple
enzymes, including glycogen
synthase, helps control the synthesis
Since the tight control of enzyme activity is The International Union of Biochemistry
essential for homeostasis, any malfunction and Molecular Biology have developed a
(mutation, overproduction, nomenclature for enzymes, the EC
underproduction or deletion) of a single numbers; each enzyme is described by a
critical enzyme can lead to a genetic sequence of four numbers preceded by
disease. The importance of enzymes is "EC". The first number broadly classifies the
shown by the fact that a lethal illness can be enzyme based on its mechanism.
caused by the malfunction of just one type
of enzyme out of the thousands of types The top-level classification is
present in our bodies.
 EC 1 Oxidoreductases: catalyze
One example is the most common type of oxidation/reduction reactions
phenylketonuria. A mutation of a single  EC 2 Transferases: transfer a
amino acid in the enzyme phenylalanine functional group (e.g. a methyl or
hydroxylase, which catalyzes the first step phosphate group)
in the degradation of phenylalanine, results  EC 3 Hydrolases: catalyze the
in build-up of phenylalanine and related hydrolysis of various bonds
products. This can lead to mental  EC 4 Lyases: cleave various bonds by
retardation if the disease is untreated.[77] means other than hydrolysis and
oxidation
Another example is when germline  EC 5 Isomerases: catalyze
mutations in genes coding for DNA repair isomerization changes within a
enzymes cause hereditary cancer single molecule
syndromes such as xeroderma  EC 6 Ligases: join two molecules
pigmentosum. Defects in these enzymes with covalent bonds.
cause cancer since the body is less able to
repair mutations in the genome. This causes The complete nomenclature can be
a slow accumulation of mutations and browsed at
results in the development of many types of http://www.chem.qmul.ac.uk/iubmb/enzy
cancer in the sufferer. me/.

Naming conventions Industrial applications

An enzyme's name is often derived from its Enzymes are used in the chemical industry
substrate or the chemical reaction it and other industrial applications when
catalyzes, with the word ending in -ase. extremely specific catalysts are required.
Examples are lactase, alcohol However, enzymes in general are limited in
dehydrogenase and DNA polymerase. This the number of reactions they have evolved
may result in different enzymes, called to catalyze and also by their lack of stability
isozymes, with the same function having in organic solvents and at high
the same basic name. Isoenzymes have a temperatures. Consequently, protein
different amino acid sequence and might be engineering is an active area of research
distinguished by their optimal pH, kinetic and involves attempts to create new
properties or immunologically. enzymes with novel properties, either
Furthermore, the normal physiological through rational design or in vitro evolution.
reaction an enzyme catalyzes may not be [78][79]
These efforts have begun to be
the same as under artificial conditions. This successful, and a few enzymes have now
can result in the same enzyme being been desiged "from scratch" to catalyse
identified with two different names. E.g. reactions that do not occur in nature.[80]
Glucose isomerase, used industrially to
convert glucose into the sweetener
fructose, is a xylose isomerase in vivo.
See also

Food portal

 List of enzymes
 Enzyme product
 Enzyme substrate
 Enzyme catalysis
 Protein dynamics
 The Proteolysis Map
 RNA Biocatalysis
 SUMO enzymes
 Ki Database
 Proteonomics and protein
engineering
 Immobilized enzyme
 Kinetic Perfection
 Enzyme engineering

References

1. ^ Smith AL (Ed) et al. (1997). Oxford

dictionary of biochemistry and
molecular biology. Oxford
[Oxfordshire]: Oxford University
Press. ISBN 0-19-854768-4.
2. ^ Grisham, Charles M.; Reginald H.
Garrett (1999). Biochemistry.
Philadelphia: Saunders College Pub.
pp. 426–7. ISBN 0-03-022318-0.
3. ^ Bairoch A. (2000). "The ENZYME
database in 2000" (PDF). Nucleic
Acids Res 28 (1): 304–5.
doi:10.1093/nar/28.1.304.
PMID 10592255. PMC 102465.
http://www.expasy.org/NAR/enz00.
pdf.
4. ^ Lilley D (2005). "Structure, folding
and mechanisms of ribozymes". Curr
Opin Struct Biol 15 (3): 313–23.
doi:10.1016/j.sbi.2005.05.002.
PMID 15919196.
5. ^ Cech T (2000). "Structural biology.
The ribosome is a ribozyme".
Science 289 (5481): 878–9.
doi:10.1126/science.289.5481.878.
PMID 10960319.
6. ^ Groves JT (1997). "Artificial
enzymes. The importance of being
selective". Nature 389 (6649): 329–