Enzymes

Introduction
- All are globular protein
- Unaltered in reactions
- Highly specific
- Little is required for catalyse because they can be reused.
- Biological catalyst (speeds up reactions)
- Lowers activation energy required.
- Active site / Substrate
- Affected by pH, temperature, substrate and enzyme
quantity.
Specificity
- Enzymes are highly specific, each recognizing a
particular substrate molecule.
- Enzymes have a unique active site with a
complementary shape to the substrate.
- This interaction is often likened to a "lock-and-key"
mechanism, where the substrate is the key that fits
perfectly into the enzyme's lock.
- Enzymes catalyze specific chemical reactions,
ensuring that only the intended reaction occurs.
- Specificity enhances the efficiency of
enzyme-substrate interactions and prevents random
or undesired reactions.
- Enzymes can repeatedly bind to and act on substrates
that match their active sites, making them efficient
catalysts for specific reactions.

Lock and Key Theory Hypothesis

- When the substrate matches the enzyme's active site,
they form an enzyme-substrate complex.
- This complex allows chemical reactions to occur more
efficiently, as it stabilizes the transition state.
- Enzymes remain unchanged after the reaction and can
be used repeatedly with new substrates that match
their active sites.
- The "Lock and Key" model
emphasizes the specificity
 and precision of enzyme-substrate interactions in
catalyzing biochemical reactions.
Activation Energy
- Chemical reactions require energy to start them ogf.
- This energy is needed to
break the existing chemical
bonds inside the molecules.
- Activation Energy can be
supplied in the form of
heat.
- Enzymes reduce the
activation energy required
for a chemical reaction to
take place.
- This means extra heat is not needed in these chemical
reactions. (Reactions can take place at lower
temperatures)
Induced Fit Hypothesis
- Sometimes, the active site and substrate may not be
exactly corresponded in shape.
- The active site of the enzyme has a more fleyshape and
is able to mold itself around the substrate.
- It only begins catalyst when it bonds closely with
substrate.
- The products no longer fit.
 -
-
- The active site and substrate are repelled and the
enzyme reverts to its original shape and is able to
attach to more substrate.
Factors Affecting Enzyme Activity
Temperature

- Enzymes have an ideal temperature range (optimal

temperature) at which they work most efficiently.
Typically, this is around the normal body temperature
for many organisms (e.g., 37°C for humans).

- Increasing temperature generally increases the rate of

enzyme-catalyzed reactions as molecules move faster
and have more kinetic energy, leading to more
frequent collisions between enzymes and substrates.

- However, at temperatures significantly above the

optimal range, enzymes denature, losing their
 three-dimensional shape, and becoming
nonfunctional. This is because high temperatures
disrupt the hydrogen and ionic bonds that maintain
the enzyme's structure.

- Enzyme activity decreases at lower temperatures due

to reduced kinetic energy and slower molecular
motion, limiting the frequency of enzyme-substrate
collisions.

- Different organisms and enzymes may have different

optimal temperature ranges based on their natural
habitats and physiological needs.
pH Levels
- Enzymes have an ideal pH range (optimal pH) at
which they function most effectively. This pH varies
among different enzymes; for example, pepsin in the
stomach works optimally at a highly acidic pH, while
trypsin in the small intestine functions best in a
slightly alkaline environment.

- pH measures the concentration of hydrogen ions (H+)

in a solution. Changes in pH can alter the charges on
amino acids within the enzyme's active site, affecting
its shape and the binding of substrates.

- Extremely high or low pH levels can disrupt the ionic

and hydrogen bonds that maintain the enzyme's
 tertiary structure, leading to denaturation and loss of
enzyme activity.

- Enzymes function less efficiently outside their optimal

pH range, with a decrease in activity due to altered
enzyme-substrate interactions.

- Biological systems often have buffer systems to help

maintain a stable pH, ensuring that enzymes can
perform optimally within a specific pH range.
Volume Of Substrate

- Enzyme activity typically increases with higher

substrate concentrations as more substrate molecules
are available for enzyme binding.

- With an excess of substrate, the rate of the reaction

initially increases in a linear manner, following the
principle of the law of mass action.

- Enzymes reach a saturation point where all active sites

are continually occupied by substrate molecules.
Beyond this point, increasing substrate volume does
not further increase the reaction rate, as the enzymes
are working at their maximum capacity.

- At low substrate volumes, enzyme activity is limited,

as there are not enough substrate molecules to occupy
 all available active sites, causing the reaction to
proceed slowly.

- The volume of substrate can impact the efficiency of

enzyme-catalyzed reactions, with optimal results
achieved at a balanced substrate-to-enzyme ratio.

Cofactors
- Cofactors are non-protein molecules that assist
enzymes in their catalytic activity.
- Some cofactors are inorganic ions, like metal ions
(e.g., Zn2+, Mg2+), which help in enzyme function by
participating in reactions or stabilizing the enzyme's
structure.
- Organic cofactors, also known as coenzymes, are
complex organic molecules (e.g., vitamins) that are
essential for enzyme activity. They often act as
carriers of specific chemical groups during reactions.
- Cofactors can facilitate enzymatic reactions by
providing necessary chemical groups or structural
support, enabling enzymes to function more
effectively.
- Enzymes often require specific cofactors to carry out
particular reactions, ensuring a high degree of
specificity in enzyme-catalyzed processes.
- Examples of coenzymes include NAD+ and NADP+
(involved in redox reactions) and ATP (providing
 energy). Metal ions like Fe2+ and Zn2+ serve as
inorganic cofactors in various enzymes.

PROSTHETICS

- Prosthetic cofactors are tightly and permanently

bound to the enzyme's structure.
- They play a crucial role in maintaining the enzyme's
structural integrity and stability.
- Prosthetic groups are directly involved in the catalytic
activity of the enzyme, often participating in the
reaction.
- Like other cofactors, prosthetic groups contribute to
the specificity of enzyme-substrate interactions.
- Example: Heme in hemoglobin (for oxygen binding)
and biotin in enzymes involved in carboxylation
reactions are examples of prosthetic cofactors.
COENZYMES

- Coenzymes, often derived from vitamins, play a

crucial role in activating enzymes by binding to them
and assisting in their catalytic functions.

- Coenzymes act as carriers of specific chemical groups,

such as electrons or functional groups, during
enzymatic reactions.
 - Coenzymes participate in a wide range of metabolic
reactions, including redox reactions, acyl group
transfers, and ATP transfer.

- Coenzymes can be used repeatedly; they accept and

release chemical groups, ensuring the continuous
functioning of enzymes.

- Different coenzymes are specific to particular enzyme

reactions, contributing to the high specificity of
enzymatic processes.
- Common coenzymes include NAD+ and NADP+
(involved in electron transfer), coenzyme A (CoA,
involved in acyl group transfers), and ATP (providing
energy).

ACTIVATORS

- Activator cofactors are molecules that, when bound to

enzymes, enhance their catalytic activity.
- Some enzymes are inactive or less active without their
specific activator cofactors.
- Activators often regulate enzyme activity by turning
enzymes on or off in response to cellular needs.
- An example is ATP, which can serve as an activator
cofactor for enzymes involved in energy-related
processes.
 - Activators are usually specific to particular enzymes,
contributing to the specificity of enzyme-catalyzed
reactions.
- Enzymes often work in concert with activators and
other cofactors to ensure proper functioning in
complex metabolic pathways.
Enzyme Inhibition
Enzyme inhibitors are molecules that interfere with the
activity of enzymes. They can either block or reduce the
enzyme's ability to catalyze a specific chemical reaction.
Enzyme inhibitors play a
crucial role in regulating
various biochemical
processes in the body and
are used in medicine to
treat conditions by
targeting specific
enzymes. There are
different types of enzyme
inhibitors, including
competitive inhibitors that
compete with the substrate for binding to the enzyme's active
site and non-competitive inhibitors that bind to other parts of
the enzyme, altering its shape and function.
Competitive inhibitors (reversible)

Competitive enzyme inhibitors are molecules that resemble

the substrate and compete for binding to the active site of an
enzyme. By occupying the active site, they prevent the
substrate from binding and reduce the enzyme's ability to
catalyze a specific reaction. Competitive inhibitors can be
overcome by increasing the substrate concentration, as this
raises the chances of substrate outcompeting the inhibitor for
the active site. These inhibitors are often used as a basis for
designing drugs that target specific enzymes to treat various
medical conditions.

Examples

1. Statins: Statin drugs are used to lower cholesterol levels in

the body by inhibiting the enzyme HMG-CoA reductase, which
is involved in cholesterol synthesis.

2. Methotrexate: Methotrexate is a competitive inhibitor of

dihydrofolate reductase, an enzyme essential for the synthesis
of DNA and RNA. It's used in chemotherapy and to treat
autoimmune diseases.

3. Allopurinol: Allopurinol is a competitive inhibitor of

xanthine oxidase, an enzyme involved in purine metabolism.
It's used to reduce uric acid levels and treat conditions like
gout.
4. Penicillin: Penicillin is a competitive inhibitor of
transpeptidase enzymes involved in bacterial cell wall
synthesis. It disrupts bacterial cell wall formation, leading to
cell lysis and antibiotic effects.

Non-competitive (irreversible)

Non-competitive enzyme inhibitors are molecules that bind to

an enzyme at a location other than the active site, causing a
conformational change in the enzyme's structure. This change
makes the active site less effective at catalyzing the reaction,
reducing the enzyme's overall activity. Unlike competitive
inhibitors, non-competitive inhibitors do not compete with
the substrate for the active site and cannot be overcome by
increasing substrate concentration. They are often used in
regulating biochemical pathways and can be valuable in drug
development for targeting specific enzymes.

Examples

1. Cyanide: Cyanide is a non-competitive inhibitor that binds to

the metal ion in the active site of cytochrome c oxidase, an
enzyme involved in the electron transport chain of cellular
respiration. This prevents the enzyme from functioning and
can be fatal.

2. Allosteric inhibitors: Many enzymes are regulated by

non-competitive allosteric inhibitors. For example, ATP can
serve as an allosteric inhibitor for phosphofructokinase, an
enzyme in glycolysis, regulating the glycolytic pathway.
3. Heavy metals: Some heavy metals like lead and mercury can
act as non-competitive inhibitors by binding to enzymes and
disrupting their function. Lead can inhibit enzymes involved in
heme synthesis, while mercury can inhibit enzymes like
acetylcholinesterase.

4. HIV protease inhibitors: Certain antiretroviral drugs used in

the treatment of HIV, such as ritonavir, act as non-competitive
inhibitors by binding to the HIV protease enzyme, disrupting
the virus's replication process.

End Product Inhibition

End product inhibition is a regulatory mechanism in
biochemical pathways where the final product of a series of
reactions acts as an inhibitor of an earlier enzyme in the
pathway. This feedback inhibition helps control the rate of the
entire pathway by preventing the overproduction of end
products. When the end product concentration reaches a
certain level, it binds to the allosteric site of the inhibitory
enzyme, causing a conformational change that reduces its
activity. This mechanism ensures that the synthesis of
essential compounds is balanced and not excessive, promoting
metabolic homeostasis.

Examples

1. Threonine synthesis: In the biosynthesis of the amino acid

threonine, the end product, threonine, acts as an inhibitor of
the enzyme threonine deaminase. This inhibition prevents the
excessive production of threonine when it is not needed.

2. Fatty acid synthesis: In fatty acid biosynthesis,

malonyl-CoA, which is an intermediate and the precursor to
fatty acids, inhibits acetyl-CoA carboxylase, an enzyme
involved in the production of malonyl-CoA. This feedback
mechanism prevents the overproduction of fatty acids.

3. Nucleotide biosynthesis: The end product, uridine

triphosphate (UTP), can inhibit the enzyme carbamoyl
phosphate synthetase II (CPS II) in the pyrimidine biosynthesis
pathway. This helps regulate the production of pyrimidine
nucleotides.

Effect of Pesticide on The Nervous System

Pesticides can have a detrimental effect on the nervous system.
Organophosphates and carbamates are common classes of
pesticides that work by inhibiting acetylcholinesterase, an
enzyme responsible for breaking down the neurotransmitter
acetylcholine. When these pesticides are ingested or absorbed,
they can lead to an accumulation of acetylcholine in nerve
synapses, causing overstimulation of nerve cells. This can
result in symptoms such as muscle tremors, seizures, and, in
severe cases, paralysis or even death. Pesticides that affect the
nervous system can pose significant health risks to both
humans and wildlife, making their proper handling and
regulation crucial for safety and environmental protection.