Enzymes: Nature's Biochemical Catalysts
ENZYMES : are effective & high specific biological
catalyst
that catalyze the conversion of one or more
compounds
(substrates) into one or more different
compounds (products)
.
enzymes are involved in all essential body reactions &
found in all body tissues
Enzymes = Life
Catalyst is a substance that causes or accelerate a
chemical reaction without itself being affected .
With a catalyst, reactions occur faster and with less
energy.
Like all catalysts, enzymes are neither consumed nor
permanently altered as a consequence of their
participation in a reaction.
Enzymes are proteins that
increase the rate of
reaction by lowering the
energy of activation
Like other catalysts,
enzymes lower activation
energy by bringing the
reactants closer together,
aligning reactants, and/or
weakening chemical
bonds so reactions
proceed faster.
Each enzyme is assigned two names:
1.
The first is its short,
Recommended
Name
, convenient for everyday use.
1.
The second is the more complicated
Systematic Name
, which is used when an
enzyme must be identified without
ambiguity.
Recommended Name
:
The commonly used names for most enzymes describe the type
of reaction catalyzed, followed by the suffix
-ase
.
For example:
dehydrogen
ase
s remove hydrogen atoms
prote
ase
s
hydrolyze proteins
isomer
ase
s catalyze rearrangements in configuration.
Modifiers may precede the name to indicate:
the substrate (
xanthine oxidase)
the source of the enzyme
(
pancreatic ribonuclease)
its regulation (hormone-sensitive lipase)
Alphanumeric designators are added to
identify multiple forms
of an enzyme (eg, RNA polymerase
III; protein kinase C ).
The
International Union of Biochemists (IUB)
developed a
clear system of enzyme nomenclature in which each
enzyme has a unique name and code number that identify
the type of reaction catalyzed and the substrates involved.
Despite the clarity of the IUB system, the names are
relatively difficult, so we generally continue to refer to
enzymes by their traditional names.
In this system enzymes are grouped into the following six
classes.
1.
Oxidoreductases:
Enzymes that catalyze oxidations and reductions.
2.
Transferase:
Enzymes that catalyze transfer of moieties such as glycosyl,
methyl, or phosphoryl groups.
3.
Hydrolases:
Enzymes that catalyze
hydrolytic cleavage of C—C, C—O, C—N
and other covalent bonds.
4.
Lyases:
Enzymes that catalyze cleavage of C—C, C—O, C—N and other
covalent bonds by
atom elimination, generating double bonds.
5.
Isomerases:
Enzymes that catalyze geometric or structural changes
within a
molecule.
6.
Ligases:
Enzymes that catalyze the joining together (ligation) of two
molecules in reactions coupled to the hydrolysis of ATP.
The IUB name for hexokinase illustrates both the clarity of
the IUB system and its complexities.
The IUB name of hexokinase is :
ATP:D-hexose 6-phosphotransferase E.C.2.7.1.1.
This name identifies hexokinase as a member of class 2
(transferases)
Subclass 7 (transfer of a phosphoryl group)
Subclass 1 (alcohol is the phosphoryl acceptor)
Subclass 1 (
indicates that the alcohol phosphorylated is on
carbon six of a hexose)
In addition to the previous nomenclature
systems
Some enzymes retain their original trivial
names, which give no hint of the associated
enzymic reaction, for example,
trypsin and
pepsin
Some enzymes need
molecules other than protein
for enzymic activity
Holoenzyme
refer to the
complete, catalytically active
enzyme with its non protein
components .
Apoenzyme (zymogen)
is the
protein portion of a holoenzyme
(i.e. the enzyme yet in an
inactive form)
Definitions and Related Terms
1- Holoenzyme & Apoenzyme:
Many enzymes contain small
non protein molecules &
metal ions
that participate directly in substrate binding or
in catalysis.
These termed
prosthetic groups, cofactors, and
coenzymes,
these extend the catalytic capabilities of the
enzymes
.
Prosthetic groups are tightly and stably incorporated into a protein's structure
by covalent or non covalent forces.
Examples include :
Pyridoxal phosphate,
Flavin mononucleotide (FMN) & flavin adenine dinucleotide (FAD),
Thiamin pyrophosphate, & biotin.
Metal ions of (Co, Cu, Mg, Mn, and Zn.)
Metal ions are the most common prosthetic groups. About one-third of all
enzymes that contain tightly bound metal ions are termed
metalloenzymes.
Metals also may facilitate the binding and orientation of substrates & the
formation of covalent bonds with reaction intermediates, or by acting as Lewis
acids or bases to render substrates more
electrophilic (electron-poor) or
nucleophilic (electron-rich), and hence more reactive.
Cofactors serve functions similar to those of prosthetic
groups, but bind in a transient, dissociable manner
either to the enzyme or to a substrate, e.g. ATP.
Unlike the stably associated prosthetic groups,
cofactors must be present in the medium surrounding
the enzyme for catalysis to occur. The most common
cofactors also are metal ions.
Enzymes that require a metal ion cofactor are termed
metal-activated enzymes to distinguish them from the
metalloenzymes for which metal ions serve as
prosthetic groups.
Coenzymes serve as recyclable shuttles—or group transfer
agents—that transport many substrates from one point within
the cell to another
.
The function of these shuttles is :
First:
They stabilize species such as hydrogen atoms (FADH)
or hydride ions (NADH) that are too reactive to persist for any
significant time period in the presence of the water or organic
molecules within cell interior.
Second:
They also serve as an adaptor or handle that facilitates
the binding of small chemical groups, such as acetate (coenzyme
A) by their target enzymes.
Other
chemical moieties transported by coenzymes include
methyl groups (folates) .
The
active site
is a region
within an enzyme that fits the
shape of substrate molecules.
Amino acid side-chains align to
bind the substrate through H-
bonding, salt-bridges, and
hydrophobic interactions, etc.
Products are released when the
reaction is complete (they no
longer fit well in the active site)
Allosteric Site:
Non-active site
May interact with other
substances resulting in
overall enzyme shape
change & inhibition or
regulation.
When a substrate (
S
) fits properly in an active site, an
enzyme-substrate (
E
S
) complex
is formed:
E
+
S
E
S
Within the active site of the
E
S
complex, the reaction occurs
to convert substrate to product (
P
):
E
S
E
+
P
The products are then released, allowing another substrate
molecule to bind the enzyme
- this cycle can be repeated millions (or even more) times per
minute
The overall reaction for the conversion of substrate to
product can be written as follows:
E
+
S
E
S
E
+
P
The reaction for the
sucrase
catalyzed hydrolysis of sucrose
to glucose and fructose can be written as follows:
E
+
S
E
S
E
+
P
1
+
P
2
where
E
=
sucrase
,
S
= sucrose,
P
1
= glucose and
P
2
= fructose
Two models are proposed :
1- The Lock-and-Key Mode
2- The Induced Fit Model
In the
lock-and-key model
of enzyme action:
- The active site has a rigid shape
- Only substrates with the matching shape can fit
- The substrate is a key that fits the lock of the active site
This is an older model, however, and does not work for all enzymes
In the
induced-fit model
of enzyme action:
- The active site is flexible, not rigid
- The shapes of the enzyme, active site, and substrate adjust to
maximumize the fit, which improves catalysis
- There is a greater range of substrate specificity
This model is more consistent with a wider range of enzymes
While Fischer's "lock and key model" accounted for the grate
specificity of enzyme-substrate interactions, the implied rigidity
of the enzyme's active site failed to account for the dynamic
changes that we now know accompany catalysis.
This was addressed by Daniel Koshland's
induced fit model,
which states that:
When substrates approach and bind to an enzyme they induce a
conformational change analogous to placing a hand (substrate) into
a glove (enzyme)
The enzyme in turn induces reciprocal changes in its substrates,
harnessing the energy of binding to facilitate the transformation of
substrates into products.
Enzymes use various combinations of four mechanisms to
catalytize a chemical reactions these are:
1.
Catalysis by Proximity
2.
Acid–Base Catalysis
3.
Catalysis by Strain
4.
Covalent Catalysis
Isoenzymes are different forms of an enzyme that catalyze
the same reaction in different tissues in the body.
They have slight variations in the amino acid sequences of
the subunits of their quaternary structure
Different isoenzymes may arise from different tissues and
their specific detection may give clues to the site of
pathology.
Pyruvate Lactate (anaerobic glycolysis)
lactate dehydrogenase (LDH), which converts lactate to pyruvate,
during anaerobic glycolysis
It is a tetrameric protein and made of
two types of subunits
namely
H = Heart, M = skeletal muscle
It exists as
5 different isoenzymes
with various combinations of H
and M subunits
LDH is elevated in myocardial infarction, blood& liver disorders
Creatine + ATP phosphocreatine + ADP
(Phosphocreatine – serves as energy reserve during muscle contraction)
Creatine kinase is a dimer made of
2
monomers
M
subunit
,
& B subunits
Three different isoenzymes are formed
The ability to assay the activity of specific enzymes in
blood aids in the diagnosis and prognosis of disease.
Deficiencies in the quantity or catalytic activity of key
enzymes can result from genetic defects, nutritional
deficits, or toxins.
The absolute specificity of enzymes is of a particular
value for using them as catalysts for specific reactions in
the synthesis of a drug or antibiotic.
Enzymes also can be employed in the clinical laboratory
as tools for determining the concentration of critical
metabolites. For example, glucose oxidase is frequently
utilized to measure plasma glucose concentration.
Enzymes are also used for the treatment of injury and
disease.
Tissue plasminogen activator (tPA) or streptokinase is
used in the treatment of acute MI, while trypsin has been
used in the treatment of cystic fibrosis
38
Prof. Dr. AHMAD NADDAF
Presence of disease
Organs involved
Aetiology /nature of disease: differential diagnosis
Extent of disease-more damaged cells-more leak
enzymes in blood
Time course of disease
Enzymes are highly specific biological catalysts essential for body reactions. Catalyzing the conversion of compounds, they lower activation energy, speeding up reactions without being consumed. Each enzyme has recommended and systematic names, following clear nomenclature by the International Union of Biochemists. Enzymes are classified into classes based on their functions, with names reflecting the type of reaction they catalyze.
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Presentation Transcript
ENZYMES : are effective & high specific biological catalyst that catalyze the conversion of one or more compounds (substrates) into one or more different compounds (products). enzymes are involved in all essential body reactions & found in all body tissues Enzymes = Life
Catalyst is a substance that causes or accelerate a chemical reaction without itself being affected . With a catalyst, reactions occur faster and with less energy. Like all catalysts, enzymes are neither consumed nor permanently altered as a consequence of their participation in a reaction.
Enzymes are proteins that increase the reaction by lowering the energy of activation rate of Like enzymes lower activation energy by bringing the reactants closer together, aligning reactants, and/or weakening bonds so proceed faster. other catalysts, chemical reactions
Each enzyme is assigned two names: 1. The first is its short, Recommended Name, convenient for everyday use. 1. The second is the more complicated Systematic Name, which is used when an enzyme must be identified without ambiguity.
Recommended Name : The commonly used names for most enzymes describe the type of reaction catalyzed, followed by the suffix -ase. For example: dehydrogenases remove hydrogen atoms proteases hydrolyze proteins isomerases catalyze rearrangements in configuration. Modifiers may precede the name to indicate: the substrate (xanthine oxidase) the source of the enzyme (pancreatic ribonuclease) its regulation (hormone-sensitive lipase) Alphanumeric designators are added to identify multiple forms of an enzyme (eg, RNA polymerase III; protein kinase C ).
The International Union of Biochemists (IUB) developed a clear system of enzyme nomenclature in which each enzyme has a unique name and code number that identify the type of reaction catalyzed and the substrates involved. Despite the clarity of the IUB system, the names are relatively difficult, so we generally continue to refer to enzymes by their traditional names. In this system enzymes are grouped into the following six classes.
1. Oxidoreductases: Enzymes that catalyze oxidations and reductions. 2. Transferase: Enzymes that catalyze transfer of moieties such as glycosyl, methyl, or phosphoryl groups. 3. Hydrolases: Enzymes that catalyze hydrolytic cleavage of C C, C O, C N and other covalent bonds. 4. Lyases: Enzymes that catalyze cleavage of C C, C O, C N and other covalent bonds by atom elimination, generating double bonds. 5. Isomerases: Enzymes that catalyze geometric or structural changes within a molecule. 6. Ligases: Enzymes that catalyze the joining together (ligation) of two molecules in reactions coupled to the hydrolysis of ATP.
The IUB name for hexokinase illustrates both the clarity of the IUB system and its complexities. The IUB name of hexokinase is : ATP:D-hexose 6-phosphotransferase E.C.2.7.1.1. This name identifies hexokinase as a member of class 2 (transferases) Subclass 7 (transfer of a phosphoryl group) Subclass 1 (alcohol is the phosphoryl acceptor) Subclass 1 ( indicates that the alcohol phosphorylated is on carbon six of a hexose)
In addition to the previous nomenclature systems Some enzymes retain their original trivial names, which give no hint of the associated enzymic reaction, for example, trypsin and pepsin
Definitions and Related Terms 1- Holoenzyme & Apoenzyme: Some molecules other than protein for enzymic activity enzymes need Holoenzyme complete, enzyme with its non protein components . refer to the catalytically active Apoenzyme (zymogen) is the protein portion of a holoenzyme (i.e. the enzyme yet in an inactive form)
Many enzymes contain small non protein molecules & metal ions that participate directly in substrate binding or in catalysis. These termed prosthetic groups, cofactors, and coenzymes, these extend the catalytic capabilities of the enzymes.
Prosthetic groups are tightly and stably incorporated into a protein's structure by covalent or non covalent forces. Examples include : Pyridoxal phosphate, Flavin mononucleotide (FMN) & flavin adenine dinucleotide (FAD), Thiamin pyrophosphate, & biotin. Metal ions of (Co, Cu, Mg, Mn, and Zn.) Metal ions are the most common prosthetic groups. About one-third of all enzymes that contain tightly bound metal ions are termed metalloenzymes. Metals also may facilitate the binding and orientation of substrates & the formation of covalent bonds with reaction intermediates, or by acting as Lewis acids or bases to render substrates more electrophilic (electron-poor) or nucleophilic (electron-rich), and hence more reactive.
Cofactors serve functions similar to those of prosthetic groups, but bind in a transient, dissociable manner either to the enzyme or to a substrate, e.g. ATP. Unlike the stably associated prosthetic groups, cofactors must be present in the medium surrounding the enzyme for catalysis to occur. The most common cofactors also are metal ions. Enzymes that require a metal ion cofactor are termed metal-activated enzymes to distinguish them from the metalloenzymes for which metal ions serve as prosthetic groups.
Coenzymes serve as recyclable shuttlesor group transfer agents that transport many substrates from one point within the cell to another. The function of these shuttles is : First: They stabilize species such as hydrogen atoms (FADH) or hydride ions (NADH) that are too reactive to persist for any significant time period in the presence of the water or organic molecules within cell interior. Second:They also serve as an adaptor or handle that facilitates the binding of small chemical groups, such as acetate (coenzyme A) by their target enzymes. Other chemical moieties transported by coenzymes include methyl groups (folates) .
The active site is a region within an enzyme that fits the shape of substrate molecules. Amino acid side-chains align to bind the substrate through H- bonding, salt-bridges, hydrophobic interactions, etc. Products are released when the reaction is complete (they no longer fit well in the active site) and
Allosteric Site: Non-active site May interact with other substances resulting in overall enzyme shape change & inhibition or regulation.
When a substrate (S) fits properly in an active site, an enzyme-substrate (ES) complex is formed: E + S ES Within the active site of the ES complex, the reaction occurs to convert substrate to product (P): ES E + P The products are then released, allowing another substrate molecule to bind the enzyme - this cycle can be repeated millions (or even more) times per minute The overall reaction for the conversion of substrate to product can be written as follows: E + S ES E + P
The reaction for the sucrase catalyzed hydrolysis of sucrose to glucose and fructose can be written as follows: E + S ES E + P1 + P2 where E = sucrase, S = sucrose, P1 = glucose and P2 = fructose
Two models are proposed : 1- The Lock-and-Key Mode 2- The Induced Fit Model
In the lock-and-key model of enzyme action: - The active site has a rigid shape - Only substrates with the matching shape can fit - The substrate is a key that fits the lock of the active site This is an older model, however, and does not work for all enzymes
In the induced-fit model of enzyme action: - The active site is flexible, not rigid - The shapes of the enzyme, active site, and substrate adjust to maximumize the fit, which improves catalysis - There is a greater range of substrate specificity This model is more consistent with a wider range of enzymes
While Fischer's "lock and key model" accounted for the grate specificity of enzyme-substrate interactions, the implied rigidity of the enzyme's active site failed to account for the dynamic changes that we now know accompany catalysis. This was addressed by Daniel Koshland's induced fit model, which states that: When substrates approach and bind to an enzyme they induce a conformational change analogous to placing a hand (substrate) into a glove (enzyme) The enzyme in turn induces reciprocal changes in its substrates, harnessing the energy of binding to facilitate the transformation of substrates into products.
Enzymes use various combinations of four mechanisms to catalytize a chemical reactions these are: Catalysis by Proximity Acid Base Catalysis Catalysis by Strain Covalent Catalysis 1. 2. 3. 4.
Isoenzymes are different forms of an enzyme that catalyze the same reaction in different tissues in the body. They have slight variations in the amino acid sequences of the subunits of their quaternary structure Different isoenzymes may arise from different tissues and their specific detection may give clues to the site of pathology.
Pyruvate Lactate (anaerobic glycolysis) lactate dehydrogenase (LDH), which converts lactate to pyruvate, during anaerobic glycolysis It is a tetrameric protein and made of two types of subunits namely H = Heart, M = skeletal muscle It exists as 5 different isoenzymes with various combinations of H and M subunits LDH is elevated in myocardial infarction, blood& liver disorders
LACTATE DEHYDROGENASE ISOENZYMES
Creatine + ATP phosphocreatine + ADP (Phosphocreatine serves as energy reserve during muscle contraction) Creatine kinase is a dimer made of 2 monomers M subunit, & B subunits Three different isoenzymes are formed
Isoenzyme Name Composition Present in Elevated in CK-1 BB Brain CNS diseases Acute myocardial infarction Myocardium / Heart CK-2 MB Skeletal muscle, Myocardium CK-3 MM
The ability to assay the activity of specific enzymes in blood aids in the diagnosis and prognosis of disease. Deficiencies in the quantity or catalytic activity of key enzymes can result from genetic defects, nutritional deficits, or toxins. The absolute specificity of enzymes is of a particular value for using them as catalysts for specific reactions in the synthesis of a drug or antibiotic.
Enzymes also can be employed in the clinical laboratory as tools for determining the concentration of critical metabolites. For example, glucose oxidase is frequently utilized to measure plasma glucose concentration. Enzymes are also used for the treatment of injury and disease. Tissue plasminogen activator (tPA) or streptokinase is used in the treatment of acute MI, while trypsin has been used in the treatment of cystic fibrosis
Presence of disease Organs involved Aetiology /nature of disease: differential diagnosis Extent of disease-more damaged cells-more leak enzymes in blood Time course of disease
