ENZYMES,

COENZYMES, &
METABOLIC
ANTAGONISM
Prepared by:
CHARLIE C. FALGUERA, RN, RM, MAN
Assistant Professor 1
UPM-SHS-ECSC

Learning Objectives
Define

enzymes and other terms commonly encountered in the discussions

Explain

the general properties of enzymes

Classify

enzymes according to the nomenclature by International Enzyme

Commission

Explain

the nature and mechanisms of action and the different theories

associated with it.

Explain

the factors affecting/influencing the rate enzyme actions

Explain

the process of enzyme inhibition and the different mechanisms involved

Describe the characteristics of the regulatory enzymes and its role in metabolic
regulation.

Cite

some important clinical applications of the enzyme chemistry

General Characteristics of
Enzymes

Enzyme

Etymology:

from Greek words en means in & zyme means

yeast.
Enzyme

an organic compound that

acts as a catalyst for

biochemical reaction.
Substrate the reactant in an
enzyme-catalyzed reaction.

Enzyme Structure
Two

General Structural Classes:

Simple

enzyme an enzyme composed only of

protein (amino acid chains).
Conjugated enzyme an enzyme that
has a nonprotein part in addition
to protein part.
Apoenzyme

the protein part

of a conjugated enzyme.
Cofactor non-protein part
of a conjugated enzyme.

Enzyme Structure
Holoenzyme

the biochemically active conjugated

enzyme produced from an apoenzyme and a cofactor.

Apoenzyme + cofactor = holoenzyme

Cofactors

provide additional chemically

reactive functional groups besides those

Present in the amino acid side chains.

Enzyme Structure
Coenzyme

a small organic

molecule that serves as a

cofactor in a conjugated
enzyme.

Nomenclature Enzymes
Three

important aspects of the enzyme-naming

process:
1.

2.
3.

The suffix ase identifies a substance as an

enzyme. The suffix in are also enzymes of the
first studied.
The type of reaction catalyzed by an enzyme is
often noted with a prefix.
The identity of the substrate is often noted in
addition to the type of reaction. Infrequently, the
substrate but not the reaction type is given.

Classification of Enzymes
1.

Oxidoreductase an enzyme that catalyzes an

oxidation-reduction reaction.

Example: Lactate dehydrogenase an

oxidoreductase that
removes hydrogen from a molecule.

Classification of Enzymes
2. Transferase an enzyme that catalyzes the transfer
of functional group from one molecule to another.
Two major subtypes:
a. Transaminase catalyzes the transfer of amino
group from one molecule to another.
b. Kinase catalyzes the transfer of a phosphate
group from ATP to give ADP and a phosphorylated
product (a product containing an additional
phosphate group).

Classification of Enzymes
3. Hydrolase an enzyme that catalyzes a hydrolysis
in which the addition of a water molecule to a bond
causes the bond to break.
Ex: Carboxyhydrases effect breaking of glycosidic
bonds in
oligo- & polysaccharides.
Proteases effect breaking of peptide linkages in
proteins.

Classification of Enzymes
4. Lyase an enzyme that catalyzes the addition of
a group to a double bond or the removal of a group
to form a double bond in a manner that does not
involve hydrolysis or oxidation.
Ex: Dehydratase effects removal of the component
of water
from a double bond.
Hydratase effects the addition of the
components of
water to a double bond.

Classification of Enzymes
5. Isomerase an enzyme that catalyzes the
isomerization (rearrangement of atoms) of a
substrate in a reaction, converting it into a molecule
isomeric itself. Theres is only one reactant and one
product in reactions where isomerases are operative

Classification of Enzymes
6. Ligase an enzyme that catalyzes the bonding
together of two molecules into one with the
participation of ATP.

Classification of Enzymes

Models of Enzyme Action

Enzymes function as catalyst are based on:
1.

Enzyme Active Site

2.

Enzyme-Substrate Complex

Enzyme Active Site

Active site the relatively small part of an enzymes
structure that is actually involved in catalysis.
The active site in an enzyme is a
three-dimensional entity formed
by groups that come from different
parts of the protein chain(s); these
groups are brought together by
folding & bending.

Enzyme-Substrate Complex
An enzyme-substrate complex the intermediate
reaction species that is formed when a substrate
binds to the active site of an enzyme.

Models of Substrate-Enzyme Binding

a. Lock-and-Key Model
the active site in the
enzyme has a fixed, rigid
geometrical conformation.
Only substrates with a
complementary geometry
can be accommodated at
such a site, much as a lock
accepts only certain key.

Models of Substrate-Enzyme Binding

b. Induced-Fit Model
allows for small changes
in the shape or geometry
of the active site of an
enzyme to accommodate
a substrate. The induced
fir is a result of the
enzymes flexibility; it
adapts to accept the
incoming substrate.

Enzyme Specificity
1.

Absolute specificity. Enzyme will catalyze a

particular reaction for only one substrate.

2.

Stereochemical specificity. An enzyme can

distinguish between stereo-isomers.

3.

Group specificity. Involves structurally similar

compounds that have the same functional group.

4.

Linkage specificity. Involves a particular type of

bond, irrespective of the structural features in the
vicinity of the bond.

Factors that Affect Enzyme Activity

Enzyme activity a measure of the rate at which an
enzyme converts substrate to products in a biochemical
reaction.
1.

Temperature a measure of the kinetic energy of

molecules.

as the temperature of an enzymatically catalyzed

reaction increases, the rate (velocity) of the reaction
increases.

Factors that Affect Enzyme Activity

1.

Temperature.

When the temperature increases beyond a certain

point, the increased energy begins to cause
denaturation of the enzymes.
Optimum temperature
the temperature at which
an enzyme exhibits
maximum activity.

Factors that Affect Enzyme Activity

2.

pH is a numeric scale used to specify the acidity

or basicity of an aqueous solution.

The charge on acidic and basic amino acids located

at the active site depends on pH.
A small changes in pH can result in enzyme
denaturation and subsequent loss of catalytic
activity.

Factors that Affect Enzyme Activity

2.

pH

Optimum pH the pH at
which an enzyme exhibits
maximum activity.

Factors that Affect Enzyme Activity

3. Substrate Concentration.
When the concentration of an enzyme is kept
constant & the concentration of substrate is
increased, the enzyme activity pattern is obtained.
Enzyme activity increases up to a certain substrate
concentration & thereafter remains constant.

Factors that Affect Enzyme Activity

3. Substrate Concentration.
As substrate concentration
increases, the point is eventually
reached where enzyme
capabilities are used to
their maximum extent.

Factors that Affect Enzyme Activity

3. Substrate Concentration.
The rate at which an enzyme accepts substrate
molecules & releases product molecules at substrate
concentration is given by its turnover number.
Turnover number the number of substrate
molecules transformed per minute by one molecule
of enzyme under optimum conditions of
temperature, pH, and saturation.

Turnover Numbers for Selected

Enzymes

Factors that Affect Enzyme Activity

4. Enzyme Concentration.
If the amount of
substrate present is kept
constant and the enzyme
concentration is
increased, the reaction
rate increases because
more substrate molecules
can be accommodated in
a given amount of time.

ENZYME INHIBITION
Enzyme inhibitor a substance that slows or stops
the normal catalytic function of an enzyme by
binding to it.
Three Modes:
1.

Reversible Competitive Inhibition

2.

Reversible Noncompetitive Inhibition

3.

Irreversible Inhibition

Reversible Competitive Inhibition

Competitive enzyme
inhibitor a molecule that
sufficiently resembles an
enzyme substrate in shape
and charge distribution that
it can compete with the
substrate for occupancy of
the enzymes active site.

Reversible Noncompetitive Inhibition

Noncompetitive enzyme inhibitor
a molecule that decreases
enzyme activity by binding to a
site on an enzyme other than the
active site. The substrate can still
occupy the active site, but the
presence of the inhibitor causes a
change in the structure of the
enzyme sufficient to prevent the
catalytic groups at the active site
from properly effecting the
catalyzing action.

Irreversible Inhibition
Irreversible enzyme
inhibitor a molecule that
inactivates enzymes by
forming a strong covalent
bond to amino acid sidechain group at the enzymes
active site.

REGULATION OF ENZYME ACTIVITY

Mechanisms involved:
1.

Feedback control associated with allosteric

enzymes

2.

Proteolytic enzymes and zymogens

3.

Covalent modifications

Allosteric Enzymes
Allosteric enzyme an enzyme with two or more
protein chains (quaternary structure) and two kinds
of binding sites (substrate & regulator).

Allosteric Enzymes
Regulators:
a.

Positive regulator (activator site) increases

enzyme activity.

b.

Negative regulator (inhibitor site) decreases

enzyme activity.

Allosteric Enzymes
Characteristics:
1.

All allosteric enzymes have quaternary structure; that is,

they are composed of 2 or more protein chains.

2.

All allosteric enzymes have 2 kinds of binding sites:

substrate & regulators.

3.

Active & regulatory binding sites are distinct from each

other in both location & shape.

4.

Binding of a molecule at the regulatory site causes

changes in the overall 3-D structure of the enzyme,
including structural changes at the active site.

Feedback Control Associated with

Allosteric Enzymes
Feedback Control a process in which activation or
inhibition of the first reaction in a reaction sequence
is controlled by a product of the reaction sequence.

Proteolytic Enzymes & Zymogens

Proteolytic enzyme an enzyme that catalyzes the
breaking of peptide bonds that maintain the primary
structure of a protein.
Zymogen (Proenzyme) the inactive precursor of
proteolytic enzyme.
Ex: Pepsinogen --- Pepsin

Covalent Modification of Enzymes

Covalent modification a process in which enzyme
activity is altered by covalently modifying the
structure of the enzyme through attachment of a
chemical group to or removal of a chemical group
from a particular amino acid within the enzymes
structure.
Ex: Phosphorylation & Dephosphorylation.

Covalent Modification of Enzymes

Antibiotics that Inhibit Enzyme

Activity
1.

Sulfa Drugs (Sulfanilamide)

- Discovered in 1932 by Gerhard Domagk (German

bacteriologist), the first antibiotics in the medical
field.
- acts as a competitive inhibitor to enzymes in the
biosynthetic pathway for converting PABA into folic
acid in bacteria.

Antibiotics that Inhibit Enzyme

Activity
2. Penicillins
- discovered by Alexander Fleming in 1928.
- structures contain a 4-membered B-lactam ring fused
with a 5-membered thiazilodine ring.
- inhibit transpeptidase through irreversible inhibition.
Transpeptidase an enzyme in bacteria that catalyzes the
formation of peptide cross links between polysaccharide
strands in bacterial cell walls. These links strengthen cell
wall thus protecting from lysis (breaking up).

Antibiotics that Inhibit Enzyme

Activity
3.

Ciprofloxacin

- a broad-spectrum antibiotic, effective against skin &

bone infections as well as GIT, GUT, & RT infections.
- effective against anthrax.
- attack the enzyme DNA gyrase in bacteria causing
disruption its structure, preventing replication &
transcription of the DNA.
DNA gyrase controls how DNA in a bacterial
chromosome coils into its tertiary structure.

Medical Uses of Enzymes

1. Used to diagnose certain diseases.

Medical Uses of Enzymes

2. Used in treatment of disease.
3. Used in clinical laboratory chemical analysis.

Thank
you!!!