8/25/2021 Chemokine | biochemistry | Britannica

Load Previous Page

keyboard_arrow_up

The mechanism of enzymatic action

An enzyme attracts substrates to its active site, catalyzes the chemical reaction by which
products are formed, and then allows the products to dissociate (separate from the enzyme
surface). The combination formed by an enzyme and its substrates is called the enzyme–
substrate complex. When two substrates and one enzyme are involved, the complex is
called a ternary complex; one substrate and one enzyme are called a binary complex. The
substrates are attracted to the active site by electrostatic and hydrophobic forces, which are
called noncovalent bonds because they are physical attractions and not chemical bonds.

zoom_in

Close Ad close

https://www.britannica.com/science/chemokine 1/16
8/25/2021 Chemokine | biochemistry | Britannica

mechanisms of enzymatic action

Mechanisms of enzymatic action (see text).
Image: Encyclopædia Britannica, Inc.

As an example, assume two substrates (S and S ) bind to the active site of the enzyme
1 2
during step 1 and react to form products (P and P ) during step 2. The products dissociate
1 2
from the enzyme surface in step 3, releasing the enzyme. The enzyme, unchanged by the
reaction, is able to react with additional substrate molecules in this manner many times per
second to form products. The step in which the actual chemical transformation occurs is of
great interest, and, although much is known about it, it is not yet fully understood. In
general there are two types of enzymatic mechanisms, one in which a so-called covalent
intermediate forms and one in which none forms.

In the mechanism by which a covalent intermediate—i.e., an intermediate with a chemical

bond between substrate and enzyme—forms, one substrate, B―X, for example, reacts with
the group N on the enzyme surface to form an enzyme-B intermediate compound. The
intermediate compound then reacts with the second substrate, Y, to form the products
B―Y and X.

Many enzymes catalyze reactions by this type of mechanism. Acetylcholinesterase is used

as a specific example in the sequence described below. The two substrates (S and S ) for
1 2
acetylcholinesterase are acetylcholine (i.e., B―X) and water (Y). After acetylcholine (B―X)
binds to the enzyme surface, a chemical bond forms between the acetyl moiety (B) of
acetylcholine and the group N (part of the amino acid serine) on the enzyme surface. The
result of the formation of this bond, called an acyl–serine bond, is one product, choline (X),
and the enzyme-B intermediate compound (an acetyl–enzyme complex). The water
molecule (Y) then reacts with the acyl–serine bond to form the second product, acetic acid
(B―Y), which dissociates from the enzyme. Acetylcholinesterase is regenerated and is again
able to react with another molecule of acetylcholine. This kind of reaction, involving the
Close Ad close

formation of an intermediate compound on the enzyme surface, is generally called a double

displacement reaction.

https://www.britannica.com/science/chemokine 2/16
8/25/2021 Chemokine | biochemistry | Britannica

Sucrose phosphorylase acts in a similar way. The substrate for sucrose phosphorylase is
sucrose, or glucosyl-fructose (B―X), and the group N on the enzyme surface is a chemical
group called a carboxyl group (COOH). The enzyme-B intermediate, a glucosyl–carboxyl
compound, reacts with phosphate (Y) to form glucosyl-phosphate (B―Y). The other
product (X) is fructose.

In double displacement reactions, the covalent intermediate between enzyme and substrate
apparently influences the reaction to proceed more rapidly. Because the enzyme is
unaltered at the end of the reaction, it functions as a true catalyst, even though it is
temporarily altered during the enzymatic process.

Although many enzymes form a covalent intermediate, the mechanism is not essential for
catalysis. One substrate (Y) reacts directly with the second substrate (X―B), in a so-called
single displacement reaction. The B moiety, which is transformed in the chemical reaction,
is involved in only one reaction and does not form a bond with a group on the enzyme
surface. The enzyme maltose phosphorylase, for example, directly affects the bonds of the
substrates (B―X and X), which, in this case, are maltose (glucosylglucose) and phosphate,
to form the products, glucose (X) and glucosylphosphate (B―Y).

Covalent intermediates between part of a substrate and an enzyme occur in many

enzymatic reactions, and various amino acids—serine, cysteine, lysine, and glutamic acid—
are involved.

The rate of enzymatic reactions

The Michaelis-Menten hypothesis

If the velocity of an enzymatic reaction is represented graphically as a function of the

substrate concentration (S), the curve obtained in most cases is a hyperbola. The
mathematical expression of this curve, shown in the equation below, was developed in
1912–13 by German biochemists Leonor Michaelis and Maud Leonora Menten. In the
equation, V is the maximal velocity of the reaction, and K is called the MichaelisClose Ad close
M M
constant,

https://www.britannica.com/science/chemokine 3/16
8/25/2021 Chemokine | biochemistry | Britannica

zoom_in

diagram of enzyme action

Curves representing enzyme action (see text).
Image: Encyclopædia Britannica, Inc.

The shape of the curve is a logical consequence of the active-site concept; i.e., the curve
flattens at the maximum velocity (V ), which occurs when all the active sites of the enzyme
M
are filled with substrate. The fact that the velocity approaches a maximum at high substrate
concentrations provides support for the assumption that an intermediate enzyme–
substrate complex forms. At the point of half the maximum velocity, the substrate
concentration in moles per litre (M) is equal to the Michaelis constant, which is a rough
measure of the affinity of the substrate molecule for the surface of the enzyme. K values
M
usually vary from about 10−8 to 10−2 M, and V from 105 to 109 molecules of product
M
formed per molecule of enzyme per second. The value for V is referred to as the turnover
M
number when expressed as moles of product formed per mole of enzyme per minute. The
binding of molecules that inhibit or activate the protein surface usually results in similar
types. Close Ad close

Enzymes are more efficient than human-made catalysts operating under the same
conditions. Because many enzymes with different specificities occur in a cell, adequate

https://www.britannica.com/science/chemokine 4/16
8/25/2021 Chemokine | biochemistry | Britannica

space exists only for a few enzyme molecules catalyzing one specific reaction. Each enzyme,
therefore, must be very efficient. One molecule of the enzyme catalase, for example, can
produce 1012 molecules of oxygen per second. The catalytic groups at the active site of an
enzyme act 106 to 109 times more effectively than do analogous groups in a nonenzymatic
reaction.

The reason for the great efficiency of enzymes is not completely understood. It results in
part from the precise positioning of the substrates and the catalytic groups at the active
site, which serves to increase the probability of collision between the reacting atoms. In
addition, the environment at the active site may be favourable for reaction—that is, acidic
and basic groups may act together more effectively there, or some strain may be induced in
the substrate molecules so that their bonds are broken more easily, or the orientation of the
reacting substrates may be optimal at the enzyme surface. The theories that have been
formulated to account for the high catalytic efficiency of enzymes, although reasonable, still
remain to be proved.

Inhibition of enzymes

Some molecules very similar to the substrate for an enzyme may be bound to the active site
but be unable to react. Such molecules cover the active site and thus prevent the binding of
the actual substrate to the site. This inhibition of enzyme action is of a competitive nature,
because the inhibitor molecule actually competes with the substrate for the active site. The
inhibitor sulfanilamide, for example, is similar enough to a substrate (p-aminobenzoic
acid) of an enzyme involved in the metabolism of folic acid that it binds to the enzyme but
cannot react. It covers the active site and prevents the binding of p-aminobenzoic acid. This
enzyme is essential in certain disease-causing bacteria but is not essential to humans; large
amounts of sulfanilamide therefore kill the microorganism but do not harm humans.
Inhibitors such as sulfanilamide are called antimetabolites. Sulfanilamide and similar
close
Close Ad
compounds that kill a pathogen without harming its host are widely used in chemotherapy.

https://www.britannica.com/science/chemokine 5/16
8/25/2021 Chemokine | biochemistry | Britannica

Some inhibitors prevent, or block, enzymatic action by reacting with groups at the active
site. The nerve gas diisopropyl fluorophosphate, for example, reacts with the serine at the
active site of acetylcholinesterase to form a covalent bond. The nerve gas molecule involved
in bond formation prevents the active site from binding the substrate, acetylcholine,
thereby blocking catalysis and nerve action. Iodoacetic acid similarly blocks a key enzyme
in muscle action by forming a bulky group on the amino acid cysteine, which is found at the
enzyme’s active site. This process is called irreversible inhibition.

Some inhibitors modify amino acids other than those at the active site, resulting in loss of
enzymatic activity. The inhibitor causes changes in the shape of the active site. Some amino
acids other than those at the active site, however, can be modified without affecting the
structure of the active site; in these cases, enzymatic action is not affected.

Close Ad close

https://www.britannica.com/science/chemokine 6/16
8/25/2021 Chemokine | biochemistry | Britannica

Such chemical changes parallel natural mutations. Inherited diseases frequently result
from a change in an amino acid at the active site of an enzyme, thus making the enzyme
defective. In some cases, an amino acid change alters the shape of the active site to the
extent that it can no longer react; such diseases are usually fatal. In others, however, a
partially defective enzyme is formed, and an individual may be very sick but able to live.

Effects of temperature

Enzymes function most efficiently within a physiological temperature range. Since enzymes
are protein molecules, they can be destroyed by high temperatures. An example of such
destruction, called protein denaturation, is the curdling of milk when it is boiled.
Increasing temperature has two effects on an enzyme: first, the velocity of the reaction
increases somewhat, because the rate of chemical reactions tends to increase with
temperature; and, second, the enzyme is increasingly denatured. Increasing temperature
thus increases the metabolic rate only within a limited range. If the temperature becomes
too high, enzyme denaturation destroys life. Low temperatures also change the shapes of
enzymes. With enzymes that are cold-sensitive, the change causes loss of activity. Both
excessive cold and heat are therefore damaging to enzymes.

The degree of acidity or basicity of a solution, which is expressed as pH, also affects
enzymes. As the acidity of a solution changes—i.e., the pH is altered—a point of optimum
acidity occurs, at which the enzyme acts most efficiently. Although this pH optimum varies
with temperature and is influenced by other constituents of the solution containing the
enzyme, it is a characteristic property of enzymes. Because enzymes are sensitive to
changes in acidity, most living systems are highly buffered; i.e., they have mechanisms that
enable them to maintain a constant acidity. This acidity level, or pH, is about 7 in most
organisms. Some bacteria function under moderately acidic or basic conditions; and the
digestive enzyme pepsin acts in the acid milieu of the stomach.

Close Ad close
Enzyme flexibility and allosteric control

The induced-fit theory

https://www.britannica.com/science/chemokine 7/16
8/25/2021 Chemokine | biochemistry | Britannica

The key–lock hypothesis (see above The nature of enzyme-catalyzed reactions) does not
fully account for enzymatic action; i.e., certain properties of enzymes cannot be accounted
for by the simple relationship between enzyme and substrate proposed by the key–lock
hypothesis. A theory called the induced-fit theory retains the key–lock idea of a fit of the
substrate at the active site but postulates in addition that the substrate must do more than
simply fit into the already preformed shape of an active site. Rather, the theory states, the
binding of the substrate to the enzyme must cause a change in the shape of the enzyme that
results in the proper alignment of the catalytic groups on its surface. This concept has been
likened to the fit of a hand in a glove, the hand (substrate) inducing a change in the shape
of the glove (enzyme). Although some enzymes appear to function according to the older
key–lock hypothesis, most apparently function according to the induced-fit theory.

Typically, the substrate approaches the enzyme surface and induces a change in its shape
that results in the correct alignment of the catalytic groups. In the case of the digestive
enzyme carboxypeptidase, for example, the binding of the substrate causes a tyrosine
molecule at the active site to move by as much as 15 angstroms. The catalytic groups at the

menu search Subscribe Login

keyboard_arrow_down
active site react with the substrate to form products. The products separate from the
PROTEIN
enzyme keyboard_arrow_downSections
surface, and the enzyme is able to repeat the sequence. Nonsubstrate & Media
molecules
that are too bulky or too small alter the shape of the enzyme so that a misalignment of
catalytic groups occurs; such molecules are not able to react even if they are attracted to the
active site.

zoom_in
Close Ad close

https://www.britannica.com/science/chemokine 8/16
8/25/2021 Chemokine | biochemistry | Britannica

diagram of induced-fit binding of a substrate to an enzyme surface

Induced-fit binding of a substrate to an enzyme surface and allosteric effects (see text).
Image: Encyclopædia Britannica, Inc.

The induced-fit theory explains a number of anomalous properties of enzymes. An example

is “noncompetitive inhibition,” in which a compound inhibits the reaction of an enzyme but
does not prevent the binding of the substrate. In this case, the inhibitor compound attracts
the binding group so that the catalytic group is too far away from the substrate to react. The
site at which the inhibitor binds to the enzyme is not the active site and is called an
allosteric site. The inhibitor changes the shape of the active site to prevent catalysis without
preventing binding of the substrate.

An inhibitor also can distort the active site by affecting the essential binding group; as a
result, the enzyme can no longer attract the substrate. A so-called activator molecule affects
the active site so that a nonsubstrate molecule is properly aligned and hence can react with
the enzyme. Such activators can affect both binding and catalytic groups at the active site.

Enzyme flexibility is extremely important because it provides a mechanism for regulating

enzymatic activity. The orientation at the active site can be disrupted by the binding of an
inhibitor at a site other than the active site. Moreover, the enzyme can be activated by
molecules that induce a proper alignment of the active site for a substrate that alone cannot
induce this alignment.

As mentioned above, the sites that bind inhibitors and activators are called allosteric sites
to distinguish them from active sites. Allosteric sites are in fact regulatory sites able to
activate or inhibit enzymatic activity by influencing the shape of the enzyme. When the
activator or inhibitor dissociates from the enzyme, it returns to its normal shape. Thus, the
flexibility of the protein structure allows the operation of a simple, reversible control
system similar to a thermostat. Close Ad close

Types of allosteric control

https://www.britannica.com/science/chemokine 9/16
8/25/2021 Chemokine | biochemistry | Britannica

Allosteric control can operate in many ways; two examples serve to illustrate some general
effects. A pathway consisting of ten enzymes is involved in the synthesis of the amino acid
histidine. When a cell contains enough histidine, synthesis stops—an appropriate economy
move by the cell. Synthesis is stopped by the inhibition of the first enzyme in the pathway
by the product, histidine. The inhibition of an enzyme by a product is called feedback
inhibition; i.e., a product many steps removed from an initial enzyme blocks its action.
Feedback inhibition occurs in many pathways in all living things.

Allosteric control can also be achieved by activators. The hormone adrenaline

(epinephrine) acts in this way. When energy is needed, adrenaline is released and activates,
by allosteric activation, the enzyme adenyl cyclase. This enzyme catalyzes a reaction in
which the compound cyclic adenosine monophosphate (cyclic AMP) is formed from ATP.
Cyclic AMP in turn acts as an allosteric activator of enzymes that speed the metabolism of
carbohydrate to produce energy. This type of allosteric regulation also is widespread in
biological systems. Thus, a combination of allosteric activation and inhibition allows the
production of energy or materials when they are needed and shuts off production when the
supply is adequate.

Allosteric control is a rapid method of regulating products continuously needed by living

things. Yet some cells have no need for certain enzymes, and it would be wasteful for the
cell to synthesize them. In this case, certain molecules, called repressors, prevent the
synthesis of unneeded enzymes. The repressors are proteins that bind to DNA and prevent
the first step in the process resulting in protein synthesis. If certain metabolites are added
to cells that need an enzyme, enzyme synthesis occurs—i.e., it is induced. Addition of
galactose to a growth medium containing Escherichia coli bacteria, for example, induces
the synthesis of the enzyme beta-galactosidase. The bacteria thus can synthesize this
galactose-metabolizing enzyme when it is needed and prevent its synthesis when it is not.
The way in which the synthesis of enzymes is induced or repressed in mammalian systems
is less understood but is believed to be similar.
Close Ad close
Different types of cells in complex organisms have different enzymes, even though they
have the same DNA content. The enzymes actually synthesized are the ones needed in a

https://www.britannica.com/science/chemokine 10/16
8/25/2021 Chemokine | biochemistry | Britannica

specific cell and vary not only for different types of cells—e.g., nerve, muscle, eye, and skin
cells—but also for different species.

In an enzyme consisting of several subunits, or chains, alteration in the shape of one chain
as a result of the influence either of a substrate molecule or of allosteric inhibitors or
activators may change the shape of a neighbouring chain. As a result, the binding of a
second molecule of substrate occurs in a different way from the binding of the first, and the
third is different from the second. This phenomenon, called cooperativity, is characteristic
of allosteric enzymes. Cooperativity is reflected by a sigmoid curve, as compared to the
hyperbolic curve of Michaelis–Menten. An enzyme of several subunits that exhibits
cooperativity is far more sensitive to control mechanisms than is an enzyme of one subunit
and hence one active site.

The first example of cooperativity was observed in hemoglobin, which is not an enzyme but
behaves like one in many ways. The absorption of oxygen in the lungs and its deposition in
the tissues is far more efficient because the subunits of hemoglobin show positive
cooperativity, so called because the first molecule of substrate makes it easier for the next
to bind.

Negative cooperativity, in which the binding of one molecule makes it less easy for the next
to bind, also occurs in living things. Negative cooperativity makes an enzyme less sensitive
to fluctuations in concentrations of metabolites and may be important for enzymes that
must be present in the cell at relatively constant levels of activity.

Some enzymes are closely associated aggregates of several enzyme units; the pyruvate
dehydrogenase system, for example, contains five different enzymes, has a total molecular
weight of 4,000,000, and consists of four different types of chains. Apparently, the
enzymes in cells may be organized by forming complex units, by being absorbed on a cell
wall, or by being isolated by membranes in special compartments. Since a pathway involves
the stepwise modification of chemical compounds, aggregations of the enzymes in a given
pathway facilitate their function in a manner similar to an industrial assembly line.Close Ad close

Daniel E. Koshland

https://www.britannica.com/science/chemokine 11/16
8/25/2021 Chemokine | biochemistry | Britannica

The Editors of Encyclopaedia Britannica

Learn More in these related Britannica articles:

cell: Matrix proteins

Matrix proteins are large molecules tightly bound to form extensive networks of insoluble fibres.
These fibres may even exceed the size of the cells themselves. The proteins are of two general
types, structural and adhesive.…

cell: Membrane proteins

Membrane proteins are also of two general types. One type, called the extrinsic proteins, is
loosely attached by ionic bonds or calcium bridges to the electrically charged phosphoryl surface
of the bilayer. They can also attach to the second type of protein, called the…

metabolism: Synthesis of proteins

Approximately 120 macromolecules are involved directly or indirectly in the process of the
translation of the base sequence of a messenger RNA molecule into the amino acid sequence of
a protein. The relationship between the base sequence and the amino acid sequence constitut…

HISTORY AT YOUR
FINGERTIPS

Sign up here to see what happened On This Day, every day in your inbox!

Email address

Sign Up

By signing up, you agree to our Privacy Notice.

Close Ad close

https://www.britannica.com/science/chemokine 12/16
8/25/2021 Chemokine | biochemistry | Britannica

Close Ad close

https://www.britannica.com/science/chemokine 13/16
8/25/2021 Chemokine | biochemistry | Britannica

CHEMOKINE
keyboard_arrow_downSections
Home keyboard_arrow_right Health & Medicine keyboard_arrow_right Anatomy & Physiology

Chemokine
biochemistry

print Print verified Cite share Share more_vert More

BY
The Editors of Encyclopaedia Britannica
View Edit History

Related Topics:
protein •
Cytokine

article FULL ARTICLE

Chemokine, any of a group of small hormonelike molecules that are secreted by cells and
that stimulate the movement of cells of the immune system toward specific sites in the
body. Chemokines are a type of cytokine (a short-lived secreted protein that regulates the
function of nearby cells) and may be described more specifically as chemotactic cytokines,
because of their ability to cause certain cells in close proximity to undergo directed
chemotaxis (cellular movement in response to chemical signals). Cells that respond to
chemokines migrate along a chemical signal gradient that is marked by increasing
chemokine concentration, such that the cells end up in areas with comparatively high
chemokine levels. In this way, chemokines that are secreted by cells at sites of
inflammation attract immune cells to those sites, thereby aiding the immune response.

Research on chemokines has helped advance medical understanding of human disease and
the human immune system. Of particular importance has been research into the
relationship between chemokines and human immunodeficiency virus (HIV), the cause of
acquired immunodeficiency syndrome (AIDS). Certain chemokines appear to be able to
close
control HIV infection, which suggests that they may be of value in the development of novel
Close Ad

treatments for HIV.

https://www.britannica.com/science/chemokine 14/16
8/25/2021 Chemokine | biochemistry | Britannica

This article was most recently revised and updated by Kara Rogers, Senior Editor.

Learn More in these related Britannica articles:

immune system

Immune system, the complex group of defense responses found in humans and other advanced
vertebrates that helps repel disease-causing organisms (pathogens). Immunity from disease is
actually conferred by two cooperative defense systems, called nonspecific, innate immunity and…

cytokine

Cytokine, any of a group of small, short-lived proteins that are released by one cell to regulate the function of
another cell, thereby serving as intercellular chemical messengers. Cytokines effect changes in cellular behaviour
that are important in a number of physiological processes, including reproduction, growth and development, and…

HIV

HIV, retrovirus that attacks and gradually destroys the immune system, leaving the host unprotected against
infection. HIV is classified as a lentivirus (meaning “slow virus”). Persons who are infected with HIV often die from
secondary infections or cancer. AIDS is the final stage of HIV…

HISTORY AT YOUR
FINGERTIPS

Sign up here to see what happened On This Day, every day in your inbox!

Email address

Sign Up

By signing up, you agree to our Privacy Notice.

Close Ad close

https://www.britannica.com/science/chemokine 15/16
8/25/2021 Chemokine | biochemistry | Britannica

Close Ad close

https://www.britannica.com/science/chemokine 16/16