Enzymes

Enzymes

Enzymes Enzymes are are proteins proteins that that catalyze catalyze chemical reactions. chemical reactions.

In enzymatic reactions, the In enzymatic reactions, the molecules molecules at the beginning of at the beginning of
the process are called the process are called substrates substrates, and the enzyme converts , and the enzyme converts
them into different molecules, called the them into different molecules, called the products products. .

Almost all processes in a Almost all processes in a biological cell biological cell need enzymes to need enzymes to
occur at significant rates. occur at significant rates.

Since enzymes are selective for their substrates and speed Since enzymes are selective for their substrates and speed
up only a few reactions from among many possibilities, the up only a few reactions from among many possibilities, the
set of enzymes made in a cell determines which set of enzymes made in a cell determines which
metabolic pathways metabolic pathways occur in that cell. occur in that cell.

Structures
Structures

Enzymes are generally Enzymes are generally globular proteins globular proteins and range from just 6 and range from just 6
amino acid residues in size to over ,!"" residues. amino acid residues in size to over ,!"" residues.

#he activities of enzymes are determined by their #he activities of enzymes are determined by their
three$dimensional structure three$dimensional structure. .

%ost enzymes are much larger than the substrates they act on, %ost enzymes are much larger than the substrates they act on,
and only a small portion of the enzyme &around '() and only a small portion of the enzyme &around '() amino acids amino acids* *
is directly involved in catalysis. is directly involved in catalysis.

%ost enzymes can be %ost enzymes can be denatured denatured+that is, unfolded and +that is, unfolded and
inactivated+by heating or chemical denaturants, which disrupt inactivated+by heating or chemical denaturants, which disrupt
the the three$dimensional structure three$dimensional structure of the protein. of the protein.

,epending on the enzyme, denaturation may be reversible or ,epending on the enzyme, denaturation may be reversible or
irreversible. irreversible.

"Lock and key" model
"Lock and key" model

Enzymes are very specific, and it was suggested by Enzymes are very specific, and it was suggested by Emil -ischer Emil -ischer
in ./0) that this was because both the enzyme and the substrate in ./0) that this was because both the enzyme and the substrate
possess specific complementary geometric shapes that fit e1actly possess specific complementary geometric shapes that fit e1actly
into one another. #his is often referred to as 2the loc3 and 3ey2 into one another. #his is often referred to as 2the loc3 and 3ey2
model. model.

Allosteric modulation
Allosteric modulation
Allosteric Allosteric enzymes change their structure in response to enzymes change their structure in response to
binding of binding of effectors effectors. .

%odulation can be direct, where the effector binds directly %odulation can be direct, where the effector binds directly
to to binding sites binding sites in the enzyme, or indirect, where the effector in the enzyme, or indirect, where the effector
binds to other proteins or binds to other proteins or protein subunits protein subunits that interact with that interact with
the allosteric enzyme and thus influence catalytic activity. the allosteric enzyme and thus influence catalytic activity.

Cofactors and coenzymes
Cofactors and coenzymes
Cofactors Cofactors

Some enzymes do not need any additional components to show Some enzymes do not need any additional components to show
full activity. 4owever, others re5uire non$protein molecules full activity. 4owever, others re5uire non$protein molecules
called cofactors to be bound for activity. called cofactors to be bound for activity.

6ofactors can be either 6ofactors can be either inorganic inorganic & &e.g. e.g., , metal ions metal ions and and
iron$sulfur clusters iron$sulfur clusters* or * or organic compounds organic compounds &e.g., &e.g., flavin flavin and and
heme heme*. *.

7rganic cofactors can be either 7rganic cofactors can be either prosthetic groups prosthetic groups, which are , which are
tightly bound to an enzyme, or tightly bound to an enzyme, or coenzymes coenzymes, which are released , which are released
from the enzyme8s active site during the reaction. from the enzyme8s active site during the reaction.

6oenzymes include 6oenzymes include 9A,4 9A,4, , 9A,:4 9A,:4 and and adenosine adenosine
triphosphate triphosphate. #hese molecules transfer chemical groups . #hese molecules transfer chemical groups
between enzymes. between enzymes.;)'< ;)'<

An e1ample of an enzyme that contains a cofactor is An e1ample of an enzyme that contains a cofactor is
carbonic carbonic anhydrase anhydrase. .

#hese tightly bound molecules are usually found in the #hese tightly bound molecules are usually found in the
active site and are involved in catalysis. active site and are involved in catalysis.

-or e1ample, flavin and heme cofactors are often involved in -or e1ample, flavin and heme cofactors are often involved in
redo1 redo1 reactions. reactions.
Coenzymes Coenzymes

6oenzymes are small organic molecules that transport 6oenzymes are small organic molecules that transport
chemical groups from one enzyme to another. chemical groups from one enzyme to another.

Some of these chemicals such as Some of these chemicals such as riboflavin riboflavin, , thiamine thiamine and and
folic acid folic acid are are vitamins vitamins &compounds which cannot be synthesized &compounds which cannot be synthesized
by the body and must be ac5uired from the diet*. by the body and must be ac5uired from the diet*.

#he chemical groups carried include the #he chemical groups carried include the hydride hydride ion &4$* ion &4$*
carried by carried by 9A, or 9A,:= 9A, or 9A,:=, the acetyl group carried by , the acetyl group carried by
coenzyme A coenzyme A, formyl, methenyl or methyl groups carried by , formyl, methenyl or methyl groups carried by
folic acid folic acid and the methyl group carried by and the methyl group carried by S$ S$
adenosylmethionine adenosylmethionine. .

Inhibition
Inhibition

Competitive inhibition
Competitive inhibition

In competitive inhibition, the inhibitor and substrate

In competitive inhibition, the inhibitor and substrate
compete for the enzyme &i.e., they can not bind at the
compete for the enzyme &i.e., they can not bind at the
same time*.
same time*.

7ften competitive inhibitors strongly resemble the

7ften competitive inhibitors strongly resemble the
real substrate of the enzyme.
real substrate of the enzyme.

-or e1ample,
-or e1ample,
methotre1ate
methotre1ate
is a competitive inhibitor
is a competitive inhibitor
of the enzyme
of the enzyme
dihydrofolate
dihydrofolate
reductase
reductase
, which
, which
catalyzes the reduction of
catalyzes the reduction of
dihydrofolate
dihydrofolate
to
to
tetrahydrofolate
tetrahydrofolate
.
.


Uncompetitive inhibition
Uncompetitive inhibition

In uncompetitive inhibition the inhibitor can not bind

In uncompetitive inhibition the inhibitor can not bind
to the free enzyme, but only to the ES$comple1.
to the free enzyme, but only to the ES$comple1.

#he EIS$comple1 thus formed is enzymatically

#he EIS$comple1 thus formed is enzymatically
inactive.
inactive.

#his type of inhibition is rare, but may occur in

#his type of inhibition is rare, but may occur in
multimeric enzymes.
multimeric enzymes.


Noncompetitive inhibition
Noncompetitive inhibition

9on$competitive inhibitors can bind to the enzyme at

9on$competitive inhibitors can bind to the enzyme at
the same time as the substrate, i.e. they
the same time as the substrate, i.e. they
never
never
bind to
bind to
the active site.
the active site.

>oth the EI and EIS comple1es are enzymatically

>oth the EI and EIS comple1es are enzymatically
inactive.
inactive.

>ecause the inhibitor can not be driven from the

>ecause the inhibitor can not be driven from the
enzyme by higher substrate concentration
enzyme by higher substrate concentration


Uses of inhibitors
Uses of inhibitors

Since inhibitors modulate the function of enzymes they are Since inhibitors modulate the function of enzymes they are
often used as drugs. often used as drugs.

An common e1ample of an inhibitor that is used as a drug is An common e1ample of an inhibitor that is used as a drug is
aspirin aspirin, which inhibits the , which inhibits the 67?$. 67?$. and and 67?$ 67?$ enzymes that enzymes that
produce the produce the inflammation inflammation messenger messenger prostaglandin prostaglandin, thus , thus
suppressing pain and inflammation. suppressing pain and inflammation.

4owever, other enzyme inhibitors are poisons. 4owever, other enzyme inhibitors are poisons.

-or e1ample, the poison -or e1ample, the poison cyanide cyanide is an irreversible enzyme is an irreversible enzyme
inhibitor that combines with the copper and iron in the active inhibitor that combines with the copper and iron in the active
site of the enzyme site of the enzyme cytochrome cytochrome c c o1idase o1idase and bloc3s and bloc3s
cellular respiration cellular respiration

Involvement in disease
Involvement in disease

Since the tight control of enzyme activity is essential for Since the tight control of enzyme activity is essential for
homeostasis homeostasis, any malfunction &mutation, overproduction, , any malfunction &mutation, overproduction,
underproduction or deletion* of a single critical enzyme can underproduction or deletion* of a single critical enzyme can
lead to a lead to a genetic disease genetic disease. .

#he importance of enzymes is shown by the fact that a lethal #he importance of enzymes is shown by the fact that a lethal
illness can be caused by the malfunction of just one type of illness can be caused by the malfunction of just one type of
enzyme out of the thousands of types present in our bodies. enzyme out of the thousands of types present in our bodies.

7ne e1ample is the most common type of 7ne e1ample is the most common type of phenyl3etonuria phenyl3etonuria. .

A mutation of a single amino acid in the enzyme A mutation of a single amino acid in the enzyme
phenylalanine phenylalanine hydro1ylase hydro1ylase, which catalyzes the first step in , which catalyzes the first step in
the degradation of phenylalanine, results in build$up of the degradation of phenylalanine, results in build$up of
phenylalanine and related products. phenylalanine and related products.

#his can lead to mental retardation if the disease is untreated. #his can lead to mental retardation if the disease is untreated.

phenylketonuria
phenylketonuria
Infants with classic :@A appear normal until they are a
few months old.
Bithout treatment with a special low$phenylalanine
diet, these children develop permanent intellectual
disability.

Industrial Application
Industrial Application
application application Enzymes used Enzymes used uses uses
!ood processin" !ood processin" .. .. Amylases from fungi and Amylases from fungi and
plants. plants.
. . proteases proteases
:roduction of sugars :roduction of sugars
from starch, such as in from starch, such as in
ma3ing high$fructose ma3ing high$fructose
com syrup. com syrup.
#aby foods #aby foods trypsin trypsin #o predigest baby food. #o predigest baby food.
#re$in" industry #re$in" industry .. .. Enzyme from barely Enzyme from barely #hey degrade starch #hey degrade starch
and proteins to produce and proteins to produce
simple sugar, amino simple sugar, amino
acids and peptides that acids and peptides that
are used by yeast for are used by yeast for
fermentation. fermentation.
. amylase, proteases . amylase, proteases Split polysaccharides Split polysaccharides
and proteins in the malt. and proteins in the malt.

application application Enzymes used Enzymes used uses uses
!ruit %uices !ruit %uices celluloses, pectinases celluloses, pectinases 6larify fruit juices 6larify fruit juices
&airy industry &airy industry Cennin, derived from the Cennin, derived from the
stomach of the young stomach of the young
ruminant animals ruminant animals
%anufacture of cheese %anufacture of cheese
'eat tenderizers 'eat tenderizers papain papain #o soften meat for #o soften meat for
coo3ing coo3ing
(aper industry (aper industry 6ellulases, ligninases 6ellulases, ligninases ,egrade starch to lower ,egrade starch to lower
viscosity, aiding sizing viscosity, aiding sizing
and coating paper. and coating paper.