Introduction to Bioengineering Theory

(BBL1020; 3-0-0)

Lecture-8: 28.08.2023

Google Classroom Code: pr4ukfr

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Chemical Kinetics
Bioenergetics
Biocatalysis
Association and dissociation constants
The general reaction form is: aA + bB → cC + dD
Reactions are categorized as zero-order, first-order, second-order, or mixed-order (higher-order) reactions.
• Zero-Order Reactions
Zero-order reactions (where order = 0) have a constant rate. The rate of a zero-order reaction is constant and independent of
the concentration of reactants. The rate law is: rate = k, with k having the units of M/sec.

• First-Order Reactions
A first-order reaction (where order = 1) has a rate proportional to the concentration of one of the reactants. A common
example of a first-order reaction is radioactive decay, the spontaneous process through which an unstable atomic nucleus
breaks into smaller, more stable fragments.
The rate law is: rate = k[A] (or B instead of A), with k having the units of sec-1

• Second-Order Reactions
A second-order reaction (where order = 2) has a rate proportional to the concentration of the square of a single reactant or
the product of the concentration of two reactants.
The formula is: rate = k[A]2, with the units of the rate constant M-1sec-1
The binding constant, or association constant, is a special case of the equilibrium constant K, and is the inverse of the
dissociation constant. It is associated with the binding and unbinding reaction of receptor (R) and ligand (L) molecules,
which is formalized as: R + L ⇌ RL (R: Receptor and L: Ligand)

The reaction is characterized by the on-rate constant kon and the off-rate constant koff, which have units of M−1 s−1 and s−1,
respectively. In equilibrium, the forward binding transition R + L → RL should be balanced by the backward unbinding
transition RL → R + L. That is,
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Association and dissociation constants
The binding constant Ka is defined by,

An often-considered quantity is the dissociation constant Kd ≡ 1/Ka, which has the unit of concentration,
despite the fact that strictly speaking, all association constants are unitless values.

•koff is the rate constant of dissociation of the drug from the receptor; kon is the
rate constant of association of the drug to the receptor.
•Dissociation constant (Kd ) is the rate constant of dissociation at equilibrium,
defined as the ratio koff / kon
•Association constant (ka or Ka ) is the opposite of Kd
• When Ka is high, Kd is low, and the drug has a high affinity for the receptor
(fewer molecules are required to bind 50% of the receptors)
•Affinity in chemistry is the tendency of dissimilar chemical species to
form chemical compounds. The major factors which affect affinity and
dissociation constant in clinical pharmacology are temperature and the
presence of a catalyst. The major factors which affect affinity and dissociation
constant are temperature and the presence of a catalyst.
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Association and dissociation constants
In general, the rate of any reaction is determined by the Arrhenius equation:

So, it is composed of several immutable constants, eg. the gas constant and temperature Within the
confines of the fragile reaction vessel which is the human body, temperature is fairly constant and
probably close to 37°C. The only things which will vary for any given chemical reaction will be Ea, which
can be reduced in the presence of a catalyst.

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Association and dissociation constants
The function of a catalyst is to lower the activation energy required by a reaction.
Therefore, the lowered activation energy (accounted by the catalyst) can be
substituted into the Arrhenius equation in order to obtain the rate constant for the
catalysed reaction.

The exponential part of the Arrhenius equation (-Ea/RT) accounts for an

exponential increase in the value of the rate constant for any decrease in the
activation energy. Since the rate of a chemical reaction is directly proportional to
the rate constant of that reaction, the decrease in activation energy results in an
exponential increase in the reaction rate.

It is important to note that the rates of uncatalysed reactions are more severely
affected by temperature than the rates of catalysed reactions. This is because the
activation energy is in the numerator of the exponential term -Ea/RT and the
absolute temperature is in the denominator. Since the activation energy of the
catalysed reaction is relatively low, the effect of temperature on the rate constant is
more visible in the corresponding uncatalysed reaction.

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Protein-ligand binding
(a) A spherical protein surrounded by point-like ligands. The binding reaction occurs as
soon as a ligand comes into contact with the protein; this scenario is modeled
mathematically by an absorbing boundary condition on the protein surface.
(b) The protein undergoing indifferent switch between two conformations. The
interconversion rates between the two conformations are the same regardless of where
the ligands are. In the inactive conformation (gray sphere), the binding reaction cannot
proceed; this situation is modeled by a reflecting boundary condition on the protein
surface. The active conformation (cyan sphere) allows the binding reaction to proceed,
as modeled by the absorbing boundary condition.
(c) Alternative pathways via which the inactive unbound protein reaches the native
complex. In the conformational-selection pathway (blue arrows), the protein first makes
the inactive-to-active transition and then loosely binds a ligand. In the induced-fit
pathway, the order of these two steps is reversed (red arrows). The loosely bound
complex converts to the native complex upon further tightening of the protein–ligand
interactions (black arrow).
(d) The protein undergoing induced switch. The interconversion rates depend on whether
there are loosely bound ligands.
The dissociation constant is commonly used to describe the affinity between a ligand (such as a drug) and a protein i.e., how
tightly a ligand binds to a particular protein. Ligand-protein affinities are influenced by non-covalent intermolecular
interactions between the two molecules such as hydrogen bonding, electrostatic interactions, hydrophobic and van
der Waals forces. Affinities can also be affected by high concentrations of other macromolecules, which causes
macromolecular crowding. The formation of a ligand-protein complex LP can be described by a two-state process where [P],
[L], [LP] represent molar concentrations of the protein, ligand and complex, respectively.

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Bioenergetics
• Bioenergetics refers to the study of
energy flow and transformation in living
organisms. This includes the processes
of energy generation, storage, and
utilization that are essential for life.
Living organisms require energy to
carry out various processes such as
growth, reproduction, and movement.

• The primary source of energy for most

living organisms is sunlight, which is
converted into chemical energy through
the process of photosynthesis in plants
and some bacteria. This chemical
energy is then transferred to other
organisms through food chains and food
webs.

• It is the quantitative study of energy

transductions in living cells.

• Types of energy: Kinetic energy

(energy in motion) and Potential energy
(stored energy). 8
Detailed examples of Bioenergetics

Photosynthesis: This is the process by which

plants and some bacteria convert sunlight into
chemical energy in the form of glucose. This
process involves the capture of light energy
by pigments such as chlorophyll, which is
then used to drive the synthesis of glucose
from carbon dioxide and water.

Cellular respiration: This is the process by

which organisms generate energy from
glucose and other organic molecules. Cellular
respiration involves the breakdown of glucose
to release energy in the form of ATP
(adenosine triphosphate). This process occurs
in the mitochondria of eukaryotic cells and in
the cytoplasm of prokaryotic cells.

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Detailed examples of Bioenergetics – Muscle contraction

• Muscle cells require large amounts of energy to

contract and produce movement. This energy is
provided by the breakdown of ATP, which is stored
in the muscle cells.

• The process of muscle contraction involves the

conversion of chemical energy stored in ATP into
mechanical energy, which is used to move the
muscles. 10
Detailed examples of Bioenergetics – Thermoregulation
Maintaining a constant body temperature requires energy. This
process involves the generation and dissipation of heat through
various mechanisms such as sweating, shivering, and changes
in blood flow. In cold environments, organisms may use
metabolic processes to generate heat and maintain their body
temperature.

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Biocatalysis- Altering the rate of biological reactions!

Catalyst-
A chemical/substance/entity that alters
the rate of a reaction and doesn’t gets
changed chemically and quantitatively
after the reaction.

Processes 2022, 10(4), 683

Biocatalysts- Doi: 10.19080/RAPSCI.2017.03.555625

Catalysts present in the biological system.

Abiotic
Centuries
The cells themselves are considered to process

act as biocatalysts. For e.g. decomposition

of organic matter. Carbohydrates Proteins

However, in the end, it's all about biomolecules

as they work for the survival and functioning
Bacteria Months
of cells.
Nucleic acids Lipids 12
Biocatalysis
In biological systems, proteins (made up of amino acids)
are the major functional molecules which perform diverse
functions ranging from signalling to catalysis.

The diversity in structure of proteins allows them to acquire

different locations and functions in an organism. The class
of proteins that take part in catalysis of reactions are known https://www.ajinomoto.com/amino-acids/what-are-amino-acids
https://www.diva-portal.org/smash/get/diva2:288611

as Enzymes. The reactants whose catalysis are done are

called substrates. Few of the properties of enzymes include-

- Complex protein molecules with high M.W.

- Very specific in their action.
- Maximally active at pH 6-8. https://www.nature.com/scitable/topicpage/protein-function-14123348/

- Are highly regulated by several factors.

- HIghly efficient and reusable.

A collection of amino acids at a particular site makes an

“Active site” of enzyme where the catalysis reaction takes
place. The weak binding interactions between the active site and
the substrate provide a substantial driving force for enzymatic
catalysis.

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Some important biocatalysts and their activities

● Lactase- the curdler.

- Converts milk into curd.

- Present throughout prokaryotes
to eukaryotes.
- Used as supplements for lactose
intolerant people. https://www2.nau.edu/lrm22/lessons/enzymes/enzymes.html

● Alcohol dehydrogenase- the winemaker.

- Catalyzes the fermentation process.

- Helps conversion of carbohydrates
into alcohols by bacteria.
- In humans, it helps the metabolism
of alcohol in liver. http://doi.org/10.2210/pdb1A4U/pdb
https://www.toppr.com/ask/content/concept/fermentation-and-its-ttypes-261206/

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Some important biocatalysts and their activities
● Carbonic anhydrase- Carbon dioxide
excretor.

- Present in RBC membranes.

- Only 15 % of carbon dioxide can be
removed from the cells of our body
through blood plasma.
- Carbonic anhydrase helps in translocation
of around 85% of carbon dioxide from cells
to lungs.
http://doi.org/10.2210/pdb6LUX/pdb
http://hyperphysics.phy-astr.gsu.edu/hbase/Organic/carbanh.html

● Lysozyme- Body’s own bacterial

terminator.

- Present in body fluids like saliva, tears etc.

- Can catalyze the breakage of bonds present
In the cell wall of bacteria.
https://www.pngwing.com/en/free-png-xwnuy/download 15
https://bmrb.io/featuredSys/Ly
sozyme/lysozyme1.shtml
ALL ENZYMES ARE PROTEINS, BUT ALL PROTEINS ARE NOT ENZYMES!!

- Carl Neuberg
(1908)
RIBOZYMES-
RNAs TURNED ENZYMES!

- Altman and Cech

(1989)

- RNAs are information containing molecules just like DNA.

- However, they have a secondary function which was discovered
much later after their discovery.
- OH groups present in their structure aid in their catalysis.
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