Bioorganic Chemistry

What is Enzyme:
Enzyme is a substance that acts as a catalyst in living organisms, regulating the rate at which chemical
reactions proceed without itself being altered in the process.

Types of Enzyme:
Enzymes are six types-
i. Oxidoreductases
ii. Transferases
iii. Hydrolases
iv. Lyases
v. Ligases
vi. Isomerases

The function of types of Enzyme:

Oxidoreductases- Oxidoreductase is an enzyme that catalyses the oxidation and reduction

reactions in which electrons are transferred from one form of a molecule (electron donor) to the other
(electron acceptor). Consider the enzyme pyruvate dehydrogenase. Cofactors for oxidoreductase
enzymes are commonly NADP+ or NAD+.
AH2+B→A+BH2

Transferases- These catalyse the transfer of a chemical group (functional group) from one
compound (referred to as the donor) to another compound (referred to as the recipient called the
acceptor). A transaminase, for example, is an enzyme that transfers an amino group from one
molecule to another.
A–X+B↔B–X+A

Hydrolases: They are hydrolytic enzymes that catalyse the hydrolysis reaction by cleaving the bond
and hydrolyzing it with water molecules. For example, they catalyse the hydrolysis of a bond. Pepsin,
for example, breaks down peptide connections in proteins.
A–X+H2O→X–OH+A–H

Lyases: They are enzymes that catalyse bodywork by creating a double bond or adding a group to a
double bond without involving hydrolysis or oxidation. Aldolase (a glycolysis enzyme) catalyses the
conversion of fructose-1, 6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone
phosphate, for example.
A–X+B–Y→A=B+X–Y

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 Bioorganic Chemistry

Isomerases: They are an enzyme family that converts a chemical from one isomer to another.
Isomerases aid intramolecular rearrangements by breaking as well as forming bonds. In
glycogenolysis, for example, phosphoglucomutase catalyses the conversion of glucose-1-phosphate to
glucose-6-phosphate (the phosphate group is moved from one position to another in the same
substance). For energy to be released fast, glycogen is converted to glucose.
ACis→A′Trans

Ligases: Ligase is a catalytic enzyme that catalyses the ligation or connecting of two big molecules
by establishing a new chemical link between them. DNA ligase, for example, catalyses the formation
of a phosphodiester bond between two DNA fragments.

A+B→AB

Factors influencing Enzyme action:

 Enzyme Concentration-
The transient bonds between enzymes and their substrates catalyze the reactions by decreasing the
activation energy and stabilizing the transition state. Given the exceeding amount of substrates and the
necessary cofactors, enzymatic reactions possessing higher enzyme concentrations will reach
equilibrium before those with the same enzyme but at lower concentrations.

Simply put, higher enzyme concentration indicates that more enzyme molecules are available to
process the substrate. The high levels of enzyme-substrate complex result in a higher initial catalytic
rate, which gives the reaction a headstart in the shift toward reactant-product equilibrium.

 Substrate Concentration-
The enzyme catalytic activity occurs when a geometrically and electronically complementary
substrate can access the enzyme’s catalytic or active site. There, the active residues transiently bond
with the substrate, catalyzing the transformation of the substrate into a product. Thus, the more
substrate-occupied active sites, the higher the catalytic activity and the faster the shift toward enzyme-
product equilibrium.
Most enzymes follow the Michaelis-Menten kinetics, which describes the relationship between
enzyme activity and substrate concentration in two stages. At the initial stage, the relationship
between the two is a linear association and plateaus when the number of unbound active sites
decreases.
Another group of enzymes, allosteric enzymes, display a sigmoidal kinetic. Initially, the relationship
between the rate of an allosteric enzyme-catalyzed reaction is exponential. However, this becomes
linear as the catalysis progresses and finally plateaus when the number of substrate-bound enzymes
becomes saturated.

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 Bioorganic Chemistry

Figure: The relationship between substrate concentration and the rate of enzyme-catalyzed reaction follows the Michaelis-
Menten kinetic in most enzymes (A) but a sigmoid curve in allosteric enzymes (B).

 pH Value-
As a chain of amino acids, proteins such as enzymes contain electrical charges from the sequence of
their amino acid residues. Most amino acids in the chain are the basis for the intramolecular
interactions that give the enzyme its three-dimensional structure. Few others act as functional
residues at the enzyme’s active site.

Altogether, the amino acids determine the substrate specificity and restrict the enzyme activity only
to a narrow range of pH. Most enzymes function optimally in slightly acidic or basic pH. However, a
few enzymes are native to extreme acidic or basic environments; hence, most active in these pH
ranges.

For this reason, a change in the pH value, either acidic or basic, affects the ionization of amino acid
residues, leading to changes in the three-dimensional structure of the enzyme. The alteration in the
enzyme conformation affects its interaction with its substrate, thus reducing its activity.

Another effect of pH change is in the enzyme’s catalytic capability. In acid-base and covalent
catalysis mechanisms, pH change can hinder or suppress catalytic activity. In extreme cases, it can
denature the enzyme, destroy its three-dimensional structure, and render it permanently non-
functional.

Enzyme of Human Funtions pH Optimal pH

In saliva, amylase breaks
ɑ-Amylase down most
polysaccharides in
6.4 - 7.0 6.6
human diets.
Pepsin is one of the
many proteases found in
the stomach’s gastric
juice. It hydrolyzes 1.5 - 4.5 2
Pepsin peptide bonds in the
protein’s amino acid
chains.
Found in the small
Trypsin intestine, trypsin is
another protease that 7.5-8.5 10
digests proteins.
Alkaline Phosphatase ALP catalyzes the
(ALP) removal of phosphate
groups from its substrate.
It is found in all human
tissue and is most 8-10 10
abundant in the intestine

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 Bioorganic Chemistry

and placenta.
Table 1:   Examples of enzymes in humans, their function, pH range, and optimal pH

 Temperature-
In the same way that pH affects enzymes, temperature also influences the stability of their
intramolecular bonds. For this reason, enzyme activity is generally more active at their optimal
temperature.
A slight increase in the temperature can speed up the reaction rate as the reactants acquire more
kinetic energy. Significant deviations from the optimal temperature, however, significantly reduce the
enzyme activity. Extreme high temperatures can destroy the intramolecular bonds and the enzyme
conformation, rendering it permanently non-functional.
Low temperature decreases the kinetic energy of the system and reduces the reaction rates. Enzyme
activity declines as the temperature gradually fall below the optimal point. Unlike the case of high
temperature, low temperature does not necessarily result in permanent enzyme denaturation, and the
enzyme activity may be restored once the temperature rises to the optimal range.
Since enzymes generally exist in aqueous solutions, a decrease in temperature upsets the nature of its
interaction with water, reducing its solubility and causing the enzyme to unfold – this ultimately
inactivates the enzyme.
However, when the temperature falls below the melting point of water (0°C or 32°F), it leads to the
formation of ice crystals that can irreversibly damage the proteins. The same effect is also seen when
frozen enzymes are thawed. The freeze-thaw damage can be avoided by minimizing freeze-thaw
cycles, freezing or thawing duration, and adding additives like sucrose or glycerol to the protein
solution.

 Effector or Inhibitor-
Many enzymes require non-substrate and non-enzyme molecules to regulate or initiate their catalytic
function. For example, certain enzymes rely on metal ions or cofactors to establish their catalytic
activity. Many rely on effectors to activate their catalytic activities, promote or inhibit their successive
binding to the substrates, as seen in allosteric enzymes.
Along the same line, inhibitors may bind to the enzyme or its substrate to inhibit the ongoing
enzymatic activity and prevent successive catalytic events. The effect on enzyme activity is
irreversible when the inhibitors form strong bonds to the enzyme’s functional group, leaving the
enzyme permanently inactive.
In contrast to irreversible inhibitors, reversible inhibitors only render the enzymes inactive when
bound to the enzyme. Competitive inhibitors compete with the substrates for binding to the residues
of the enzyme functional group at the catalytic sites. Other types of inhibitors do not bind to the
catalytic site, but they bind to the non-substrate binding allosteric site.
If an inhibitor binds to the enzyme concurrently with the enzyme-substrate binding, it is non-
competitive. If an inhibitor binds only to a substrate-occupied enzyme, it is uncompetitive.

References:

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 Bioorganic Chemistry

https://www.britannica.com/science/enzyme
https://www.geeksforgeeks.org/enzymes-definition-structure-classification-examples/
https://conductscience.com/factors-that-affect-enzyme-activity/