Module 3

Section 2

Enzymes, Bioenergetics and Metabolism in the Cell

This module will help you gain knowledge on the enzymes and their roles in the chemical
reactions that make life possible. Enzymes are specialized class of proteins responsible for catalyzing
chemical reactions within the cell and thus are ideal drug targets (Sciencedirect.com). Bioenergetics
describe the concept of energy flow through the cells. Cellular processes such as building and breaking
down of complex molecules occurs through stepwise chemical reactions and this requires energy to
proceed. Metabolism is the total of all chemical reactions that takes place in the cell –continuous
production of energy to replenish used up energy in chemical reactions and the consumption and
generation of energy.

Learning Outcomes:

After examining this module, you are expected to:

1. Assess the cellular components in relation to their functions in bioenergetics, metabolism and
respiration

Content/Information Sheet:
A. Enzymes:
Biological catalyst is known as enzymes. Enzymes catalyze many biochemical transformations in
living cells, the most fundamental are those which capture energy from nutrients. Enzymes are catalysts
that, within the mild conditions of temperature, pH and pressure of the cells, carry out chemical
reactions at amazing high rate characterized by efficiency and specificity. Enzymes are categorized under
protein that act as catalyst to speed up reactions and perform the critical task of lowering the activation
energy of chemical reactions inside the cell. Enzymes are essential parts of many metabolic pathways
and are imports to both anabolic and catabolic reactions. Without enzymes to speed up reactions, life
could not persist.

Properties of Enzymes:
1. Required in small amounts
2. They are not altered irreversibly during the reaction course
3. No effect on thermodynamics of reaction i.e. Enzymes do not supply energy for a chemical
reaction
Capabilities of enzymes:
1. Enzymes accelerate reaction factors from 10(9-20), allowing millions of reactions necessary in
your body to proceed over short period of time.
2. Enzymes recognize substrates, the reactions of the chemical reactions it catalyzes with
sensitivity. Some are specific that they will not recognize a molecule different from its preferred
substrate.

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 3. However, enzymes, alter thermodynamics of a reaction. Enzymes help reactant and products of
a reaction to reach equilibrium much faster than otherwise would happen but it does not alter
the equilibrium concentrations
4. Enzymes act in same way as all catalysts do by stabilizing transition state of a reaction.

Functions enzymes:
1. Helps in signal transduction
2. Breakdown large molecules into smaller substance that can be easily absorbed by the body
3. Help generate energy in the body
4. Responsible for movement of ions across the plasma membrane
5. Perform number of biochemical reactions including oxidation, reduction, hydrolysis to eliminate
non-nutritive substance from the body
6. Reorganize the internal structure of the cell to regulate cellular activities

How enzyme speed up reactions:

- By binding to the reactant molecules and hold them to make the chemical bond breaking and
forming processes
Note:
a. Enzymes do not change the reaction (either exergonic or endergonic)
b. Do not change the free energy of reactants and products
c. Reduce the activation energy required for the reaction to go forward
d. Enzymes is unchanged by the reaction it catalyzes

Types of Enzymes:

Majority of enzymes are proteins structurally.

Ribozymes – RNA molecules with catalytic activity.
Coenzymes are small no proteins molecules that are associated to some enzymes, many of these are
related to vitamins. Undergo changes to compensate for the transformation occurring in the substrate.
Apoenzyme – coenzymes and protein portion with catalytic activity forming the holoenzyme. This is
responsible for the enzyme’s substrate specificity
Metalloenzyme – enzymes that contain metal ions
Zymogens or proenzymes – are inactive precursors of enzymes., acquire activity after hydrolysis of a
portion of their molecule.

Structure of an enzyme:
1. Substrates- substances on which enzymes act
2. Active site or catalytic site – is the specific place in the enzyme where substrate binds; part of
molecule that has definite shape and functional group for the binding of reactant molecules

The substrate and the enzyme form an intermediate reaction with low activation energy without any
catalysts.

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Source : Enzymes – Structure, Classification and Function Retrieved from :
https://www.google.com/search?q=enzymes+%2B+byju%27s&oq=enzymes+%2B+byju%27s&aqs=chrome..69i57j0l3.6841j0j7&sourceid=chrom
e&ie=UTF-8

Figure 1. Mechanism of Enzyme reaction.

Basic mechanism of action is to catalyze the chemical reactions which begins with the binding of the
substrate with the active site of the enzyme.

Enzyme Kinetics
Activity of an enzyme is determined by measuring the amount of product formed or substrate
consumed in a reaction in a given time. The rate of enzymatic reaction is directly proportional to the
amount of enzyme present in the sample.

1. The mechanism of action of enzymes depends on ability of enzymes to accelerate the reaction
rate by decreasing the activation energy- energy between molecules to overcome the barrier in
the reaction
2. During the course of reaction, the enzyme E binds to the substrate(S) and forms a transient
enzyme-substrate complex(ES)
3. At the end of the reaction, the products are formed, the enzymes remains unchanged , can bind
another substrate and can be reused again.

The structural complementarity between enzyme and substrate allows exact reciprocal fit.
The mathematical description of enzyme action was developed by Leonor Michaelis and Maud Menten
in 1913. It uses two constants the maximum velocity (Vmax) and Michaelis constant(Km) to understand
enzyme activity on the macro scale and understand effects of different types of enzymes inhibitors.

Maximum Velocity:
1. Rate of reaction of under saturation point of enzyme’s active site
2. Increase the substrate concentration indefinitely
3. Does not increase the rate of an enzyme-catalyze reaction beyond a certain point

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Michaelis constant:
1. Substrate concentration at which half the enzymes’s active sites are occupied by substrate.
Since enzymes have varying tendencies to bind their substrates(affinities)
2. High Km = lots of substrates must be present to saturate the enzyme, low enzyme affinity’s to
the substrate
3. Low Km = only a small amount of substrate is needed to saturate the enzyme, high affinity or
substrate

Enzyme Action Models

- Enzymes interact with substrate to accelerate chemical reactions and achieve specificity:

1. Emil Fischer(1890)- proposed that substrate of an enzyme fits into the enzyme’s active
site(physical location where reaction takes place) and form an enzyme-substrate complex. This
model is analogous to lock and key where the key as the substrate has specific
shape(arrangement of functional groups and other atoms) that allows it and no other key for fit
into the lock, which is the enzyme.

Features of the Lock and Key fit:

A. Substrate and enzyme complement each other.
B. It can fit together like lock and key
C. Different molecules do-not complement the enzymes active site.

2. Daniel E. Koshland Jr. (1958) – modified the lock and key model by proposing that binding of the
substrate to the enzymes alters the configuration of both providing a better fit. This model is
know as the induced fit model.

Features:
1. The substrate and enzymes do not exactly fit each other before the binding.
2. The binding of the substrate to the enzyme changes the configuration of both so that they
fit together .
3. Different molecules cannot induce a fit with the enzyme.

Therefore,
A. the substrate is distorted (atoms are shifted, bonds are stretched and reactive groups are
brought close together to resemble the transition state of the reaction.
B. Only molecule with correct functional groups in the correct configurations are able to be
induced to fit the active site of the enzyme

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Source: 4.1: Energy and Metabolism:
https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Concepts_in_Biology_(OpenStax)/4%3A_How_Cells_Obta
in_Energy/4.1%3A_Energy_and_Metabolism

Figure 2. Induced- fit model (explains how enzymes and substrates undergo modifications during the
transition state to increase affinity of the substrate for the active site.

Cellular need and conditions constantly vary from cell to cell and change within individual cells over
time. Sometimes enzymes need to be turned off. Enzymes evolved mechanisms to be turned. Via the
molecule inhibitors that bind to an enzyme and prevent catalyze growth reactions.

Kinds of Inhibitors:
1. Irreversible- permanently inactivate the enzyme
2. Reversible- consist of:
A. Competitive Inhibitors: a molecule similar to the substrate but unable to be acted on by the
enzyme competes with the substrate for the active sites. With inhibitor, fewer active sites
are available to act on the substrate
*enzymes overall structure is unaffected by the inhibitor, the enzyme is able still to catalyze the
reaction on substrate molecules that do bind to an active site.
This inhibition is overcome by raising the substrate concentration
***Increase the KM but not the Vmax, its action is reversed by increasing S. some have similarity
to substrate and compete with it for the active site
B. Non-competitive inhibition: molecule binds to an enzyme somewhere other than the active
site called the allosteric site. This changes the enzyme’s 3D structure (active site can still
bind substrate with usual affinity but no longer the optimal arrangement to stabilize the
transition state and catalyze the reaction. This inhibition can’t be overcome by raising the
substrates concentration like competitive inhibition can. This inhibition is known as
allosteric inhibition. Allosteric activators bind to locations on an enzyme away from the site,
inducing a conformational change that increases the affinity of the enzyme’s active sites for
its substrates.
***Bind to the enzyme in a site different to the catalytic center. They decrease Vmax, leave
Km unaffected and are not influenced by S

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Source: 4.1: Energy and Metabolism:
https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Concepts_in_Biology_(OpenStax)/4%3A_How_Cells_Obta
in_Energy/4.1%3A_Energy_and_Metabolism
Figure 3. Allosteric inhibition- induces a conformational change to the active site such that
the substrate no longer fits. Allosteric activation, the activator molecule modifies the shape
of the active site to allow a better fit of the substrate.

C. Mixed inhibitors : some have effects of both competitive and non-competitive, that is they
affect both the enzyme’s affinity for substrate and the maximal rate of catalysis
D. Anticompetitive – reduce Km and Vmax

Regulation of Enzymes:
- Enzymes are subjected to regulation to adapt to the requirements of different cells.
1. Change in substrate concentration - When substrates in the cell is below the Km changes in S
modify the activity
2. Covalent modifications(phosphorylation) -changes enzyme activity
3. Allosteric factors that bind to a place in the enzyme different to the active site

Factors affecting Enzyme Activity:

1. Temperature – enzyme activities are accelerated with increasing temperatures. High
temperatures results to drastic decrease in the activity with the denaturation of enzymes.;
purified enzymes denature quickly in diluted solutions compared to enzymes in crude extracts.
Enzymes are also denaturated when it is incubated for long durations
2. pH – enzymes are sensitive to pH changes, most enzymes have their pH –optimum to neutrality.
Changes in pH causes the ionic state of amino acid residues to change in the whole protein and
in the active site, thus modifying catalysis and substrate binding.

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Source: 4.1: Energy and Metabolism:
https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Concepts_in_Biology_(OpenStax)/4%3A_How_Cells_Obta
in_Energy/4.1%3A_Energy_and_Metabolism
Figure 4. Enzymes require optimum temperature or pH for their action.

3. Preference of substrate concentration- critical at lower concentrations, the rate does not
depend on any increase in the concentration of the substrate. Enzymes have saturation point:
once all enzymes added are occupied by the substrate molecules, its activity will stop. Type of
substrate affects the enzyme action – can be inhibitors.
4. Active site – enzymatic catalysis depends upon the activity of the amino acid side chains
assembled in the active site. Enzymes bind the substrate into a region of active site in an
intermediate conformation.
5. Salt concentration – changes in salinity can either add or remove cations and anions by
disrupting the bonds resulting to distorted 3D shape. Disrupted shape disrupts attraction
between charged amino acids, denature the protein, thus, enzymes are intolerant of extreme
salinity.
6. Cofactors or coenzymes – inorganic ions and organic helper molecules, those with basic atomic
structure made up of C and H. They participate in reactions without being changed themselves
and are ultimately recycled and reused. Enzymes function is regulated by the abundance of
various cofactors and coenzymes which may be supplied by an organism’s diet or being
produced by the organism.
Vitamins= sources of coenzymes

*** Enzymes are chemical catalysts that speed up chemical reactions by lowering their activation energy.
Enzymes have an active site with a unique chemical environment that fits particular chemical reactants
for that enzyme, called substrates. Enzymes and substrates are thought to bind according to an induced-
fit model. Enzyme action is regulated to conserve resources and respond optimally to the environment.

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B. Bioenergetics:
-study of various types of energy transformations occurring in living organism
-genetic instructions flow from nucleus to cytoplasm and a cell acquires and expends energy to
maintain high level of energy
- concept of energy flow through cells.

Thermodynamics: study of energy and energy transfer involving physical matter and surroundings;
where matter is called system( relevant to a particular case of energy transfer) and surroundings is
everything outside of the matter,

Types of systems:
1. Open system – energy can be exchanged with its surroundings ex. Biological organisms
Why? Energy is exchanged between the organism and the surroundings by using energy for the
sun to perform photosynthesis or consume energy-storing molecules and release energy to the
environment through work and heat release
2. Closed system – cannot exchange energy with its surroundings

 The challenge for all living organisms is to obtain energy from their surroundings in forms that
they can transfer or transform into usable energy to do work. Living cells have evolved to meet
this challenge.
 Chemical energy stored within organic molecules(sugars and fats) is transferred and
transformed through series of cellular chemical reactions into energy within molecules of ATP
 ATP is easily accessible to do work

Energy transformations

Chemical energy Kinetic energy

Chemical energy> kinetic energy

Light energy chemical energy

Source: 4.1: Energy and Metabolism:
https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Concepts_in_Biology_(OpenStax)/4%3A_How_Cells_Obta
in_Energy/4.1%3A_Energy_and_Metabolism

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Laws of Thermodynamics and the Concept of Entropy
 Energy- capacity to do work, -capacity to change or move something

 Thermodynamics – study the changes in energy that accompany events in the universe, govern
the transfer of energy in and among all systems in the universe
I. First Law of Thermodynamics:
a. Law of Conservation of Energy
- Energy can be neither created nor destroyed
- Can be converted or transduced from one form to another
- Chemical energy stored in certain biological molecule like ATP is converted to mechanical
energy when organelles move
- Electrical energy flows across the membrane
- Thermal energy when heat is released during the muscle contraction
- Most important energy – transduction/conversion of sunlight into chemical energy-
PHOTOSYNTHESIS= Fuels nearly all forms of life
- Total amount of energy in the universe is constant
b. System and surroundings(energy transformations in matter)
System- can be a space or certain amount of matter
- Can be a living cell
- First law explains that even when the system’s energy may be lost or gained = there must be
balance with loss or gain of surroundings as well – thus, amount of energy in universe is
constant
- Internal energy= energy of the system
- ∆E – change of internal energy during transformation
*Q (heat energy) – W (work energy) = ∆E
=can be greater than or equal to , less than its internal energy from the start
= can be zero, negative or positive
- No change in pressure or volume, no work is done by the system on its surroundings (vice versa)
- Internal energy will be greater if heat is absorbed= will be less if heat is released
- Exothermic= release heat
- Endothermic = gain heat

II. Second Law of thermodynamics

- In very energy transfer, some amount of energy is lost in unusable form known as heat energy
- Heat energy is the energy transferred from one system to another that is not work.
- Events in the universe have direction – tend to proceed “downhill” from state of higher energy
to a lower one
- Any energy transformation there is decreasing availability of energy for doing additional work
- Opposite charges normally move together and not apart
- =heat flows from a warmer to cooler body , not reverse
- Spontaneous= indicates they are thermodynamically favorable and can occur without in out of
external energy
- Impossible to construct perpetual motion machine:
*Some energy is inevitably lost in input and output of energy
*Same for living organism

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 - Entropy – measure of randomness or disorder within a system; measures gain in disorder i.e.
random movements of particles of matter at random and cannot be made to accomplish directed
work
Examples of Entropy:
1. Release of heat from oxidation of glucose within a cell from friction generated as blood flows
through a vessel = increase entropy
2. Release of thermal energy by living organisms increases rate of random movement of atoms
= entropy increases with temperature
=entropy is only at absolute 0 when movements cease
- Second law indicates that only total entropy in the universe must increase, the disorder within
one part of the universe (the system can decrease as the greater expense of its surroundings
- Living organisms are able to decrease their own entropy by increasing entropy of their
environment, How?
- Entropy is decreased in an organism when relatively simple molecules are ordered into more
complex molecules ex. – amino acids > myoglobin for muscles
- In order for this to happen: entropy of environment must increase- through complex process
where ordered molecules such as glycogen stored in the liver or muscle tissue are converted
into heat and smaller and less ordered compounds (carbon dioxide and water) are released to
the environment
With such scenario= this is a feature of metabolism that makes us maintain ordered and improbable
state of at least for a while,
- Information content of macromolecules
- Measure of the energy state of living organism
- Information can be measured in terms of the ordered arrangement of a structure’s subunits
Example:
Proteins and nucleic acids with specific linear sequence of subunits is highly ordered = low
entropy and high in formation content
Therefore, low entropy results to high information content
To maintain this:
- Requires input of energy
- Maintain low random state, needs high energy

Example: different proteins has only one job to patrol the DNA looking for damage and repairing it-
expend energy so DNA content won’t deteriorate

Potential and Kinetic energy:

Potential Energy : energy stored in an object due to its position or arrangement
Kinetic Energy: energy associated with objects in motion

Free Energy – energy associated with chemical reaction that is available after the losses are accounted
for. It is the usable energy or energy that is available to do work
1. First and second laws of thermodynamics indicate that energy of universe is constant and
entropy increases to a maximum
Equation:
∆H = ∆G + T∆S = total energy is equal to the sum of the changes in useful energy and energy
that is unavailable to do further work,
where:

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 ∆H = change in enthalpy or total energy content of the system same as ∆E
∆G = change in free energy, useful energy
T= absolute temperature
∆S= change in entropy of the system

Thermodynamically favored process = exergonic( processes that occur spontaneously), negative in

change of free energy, products have less stored energy than the reactants, require small amount of
energy input to get going before it can proceed with energy releasing steps
- ∆H = ∆G - T∆S= measure spontaneity of process
-predicts direction in which a process will proceed and extent to which that process will occur
-all spontaneous energy transformations must have negative ∆G- toward lower free energy
-magnitude of ∆G
Thermodynamically unfavored =non-spontaneous, positive change in free energy, products have more
free energy than the reactants, energy storing molecules
- Enthalpy = positive ∆H-heat is gained by system and negative if heat is lost
- Entropy = positive ∆S system is more disordered and negative if it becomes ordered
- Relationship of ∆H and ∆S results to :
- Ice water transformation
- Water from liquid to solid = decrease in entropy, negative ∆S and decrease in enthalpy ∆H
- At high temperature – entropy term is more negative than enthalpy thus free energy is positive-
not spontaneous
Activation energy = small amount of energy input necessary for all chemical reactions to ccur

Free energy change in chemical reactions:

*** In studying energy, the system - the matter and environment involved in energy transfers. Entropy is
a measure of the disorder of a system. The physical laws that describe the transfer of energy are the laws
of thermodynamics. The first law states that the total amount of energy in the universe is constant. The
second law of thermodynamics states that every energy transfer involves some loss of energy in an
unusable form, such as heat energy. Energy comes in different forms: kinetic, potential, and free. The
change in free energy of a reaction can be negative (releases energy, exergonic) or positive (consumes
energy, endergonic). All reactions require an initial input of energy to proceed, called the activation
energy.

III. Metabolism:
- Total amount of biochemical reactions involved in maintaining the living conditions of the cells
in an organism.
- Chemical reactions that take place inside the cells, including those that consume or generate
energy
- All living organisms require energy for different essential process and for producing new
substances
- Help in growth, reproduction and maintaining the structure of living organisms.

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 Source: Metabolism. Byju. Retrieved from: https://byjus.com/biology/metabolism/

Figure 5. Metabolic Basis for Living

Metabolic process:
- This involves the breaking and making of molecules.
a. Catabolism – breaking of bonds, breaking of biomolecules into smaller molecules with
release of energy
Example: Glycolysis- complex 6C glucose molecule is reduced to 3C pyruvic acid

b. Anabolism – making of bonds, building up or synthesizing of new compounds from simpler

substances required by the cells which requires and stores energy.

Source: Metabolism. Byju. Retrieved from: https://byjus.com/biology/metabolism/

Figure 6. Metabolic process.

 All metabolic changes take place in multiple reactions and follow a particular metabolic
pathway.
 Metabolic pathway includes a series of reactions which are all catalyzed by a set of enzymes.

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  Metabolism is enzyme c-catalyzed reaction which provides biomolecules, needed by cells for
growth, maintenance and repair.

Purposes of Metabolic Pathways:

1. Extract energy from food for cellular activities
2. Convert food to building blocks, to synthesize biomolecules
3. Eliminate waste and toxic products

Feedback Inhibition in Metabolic Pathways

Molecules can regulate enzyme function in various ways. The most relevant sources of regulatory
molecules with respect to enzymatic cellular metabolism are the products of the cellular metabolic
reactions themselves. Cells have evolved to use the products of their own reactions for feedback
inhibition of enzyme activity. Feedback inhibition involves the use of reaction product to regulate its
own further production. The cell responds to an abundance of the products by slowing down
production during the anabolic or catabolic reactions. Feedback iinhibition is an important regulatory
mechanism in cells.

Source: 4.1: Energy and Metabolism:

https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Concepts_in_Biology_(OpenStax)/4%3A_How_Cells_Obta
in_Energy/4.1%3A_Energy_and_Metabolism

Figure 7. Feedback inhibition in metabolic pathway.

*** Cells perform the functions of life through various chemical reactions. A cell’s metabolism refers to
the combination of chemical reactions that take place within it. Catabolic reactions break down complex
chemicals into simpler ones and are associated with energy release. Anabolic processes build complex
molecules out of simpler ones and require energy.

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References:
Book/s:
Karp G. 2005. Cell and Molecular Biology: Concepts and Experiments. 4th ed. John Wiley and Sons, Inc.

Online Resources:
Metabolism. Byju. Retrieved from: https://byjus.com/biology/metabolism/

4.1: Energy and Metabolism:

https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Concepts_in_Biol
ogy_(OpenStax)/4%3A_How_Cells_Obtain_Energy/4.1%3A_Energy_and_Metabolism

CH3. Bioenergetics, Enzymes and metabolism. Dr. Hunter Cell Biology. Retrieved from:
https:////sites.google.com/site/drhunterscellpage/bio-energetics

Enzymes – Structure, Classification and Function. Byju. Retrieved from:

https://byjus.com/biology/enzymes/

Entropy. The advantages of Being Disorganized. Retrieved from:

http://www.bioinfo.org.cn/book/biochemistry/chapt13/bio2.htm

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