Mulungushi University

School of Medicine and Health Sciences

Pharmacy program

Dr. Sepiso K. Masenga

1.0 Bioenergetics
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Topic Outline
• Biological energy transformations principles
• High energy compounds
• Biochemical Redox reactions principles

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 OBJECTIVES
• Laws of thermodynamics and how they apply to biologic
systems.

• Explanation of free energy, entropy, enthalpy, exergonic,

and endergonic reactions in biochemistry with emphasis on
how reactions that are endergonic may be driven by
coupling to those that are exergonic in biologic systems or
reactions.

• The role of Adenosine triphosphate (ATP), and other

nucleotide triphosphates as group transfer potential, in the
transfer of free energy from exergonic to endergonic processes,
enabling them to act as the “energy currency” of cells
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Introduction to Biochemistry
• Biochemistry is the study of chemical and biological
substances and processes in living organisms
throughout the span of life.

• Structure, property, function, processes (metabolism)

• Normal biochemical processes are the basis of health

and disease

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Bioenergetics
• Energy formation, transformation and Utilization

• Thermodynamic principles

• Redox reactions/endergonic-exergonic reactions

• Throughout metabolism

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Terminologies
• Gibbs energy/ free energy: Energy available to expend
or we can say a thermodynamic potential that can be used
to calculate the maximum of reversible work that may be
performed by a thermodynamic system at a constant
temperature and pressure
• Gibbs change in free energy (∆G): the available portion
of the total energy change in a system required to carry a
biological or mechanical process also termed the useful
energy or chemical potential

• Chemical energy is the potential of a chemical substance

to undergo a transformation through a chemical reaction
to transform other chemical substance
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Terminologies
• Standard-state free energy of reaction (∆Go) is the free energy of
reaction at standard state conditions: [1.0 mol/L], partial pressures of
gases 0.1 MPa.
• Endergonic reaction is a reaction where energy is gained (Anabolic
reactions)
• Exergonic reaction is a reaction where energy is released (Catabolic
reactions)
• Phosphagens are also known as macroergic compounds, are energy
storage compounds, also known as high-energy phosphate
compounds, chiefly found in muscular tissue in animals.
• Oxidation is the loss of hydrogen atoms and the gain of oxygen
atoms. The opposite is true for reduction
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Terminologies
• Redox (reduction–oxidation) reactions is a chemical
reaction which involves both a reduction process and
a complementary oxidation process, two key concepts
involved with electron transfer processes.

• Group transfer potential - The Gibbs energy change

(free energy change, ΔG) occurring when a group is
transferred from a donor compound to the
nucleophile water

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Terminologies
• Thermodynamics is a branch of physical science dealing
with heat energy as it relates to other forms of energy
• Thermodynamic laws are laws that define or describe
fundamental physical quantities (temperature, energy, &
entropy) and how these quantities behave under various
circumstances
• Enthalpy is a thermodynamic quantity equivalent to the
total heat content (H) of a system
• Entropy is the extent of disorder or randomness of the
system and becomes maximum as equilibrium is
approached
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Principles
• Laws of thermodynamics
1. First law (law of conservation of energy): the total
energy of a system, including its surroundings, remains
constant
2. Second law: The total entropy of a system must increase
if a process is to occur spontaneously or entropy of any
isolated system always increases.
3. Third law: The entropy of a system approaches a constant
value as the temperature approaches absolute zero
4. Zeroth law: If two thermodynamic systems are each in
thermal equilibrium with a third, then they are in thermal
equilibrium with each other
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Bioenergetics Calculations
• Free-energy change and biological reactions rtp
• ΔG = ΔH – TΔS or ΔG = ΔE – TΔS
• Where T is the absolute temperature and H is enthalpy; In biochemical
reactions, ΔH is approximately equal to the total change in internal
energy (ΔE) of the reaction thus can also be replaced by ΔE

• The standard free-energy change (ΔG0)

―Gibbs free energy change of reaction at standard states
―concentrations of 1.0 mol/L; pH of 7.0; ~ 100kPa and 25oC
– ΔG0= ‒RT InK
– where R is the gas constant (8.314J/mol―K) and T is the absolute temperature
(Kelvin). InK is natural log of equilibrium constant
– The magnitude of ∆Go measures how far a reaction is from
equilibrium
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Bioenergetics
• Enthalpy, H
• Heat content of reaction system
• Internal energy ( number and kinds of chemical bonds btn
reactants and products)
• H>0 – endothermic (heat absorption, cools surrounding) –
not favorable
• H<0 – exothermic (heat release, warms surrounding) -
favourable
• Entropy
• Quantitative expression for amount of disorder or
randomness of a system

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 General principles

Go Enthalpy Entropy Reaction comment

<0 Ho < 0 So > 0 Spontaneous Loss of free
favorable→ energy
(Exergonic)
>0 Ho > 0 So < 0 Non- Requires
unfavorable spontaneous energy to
→ (endergonic) proceed
(endergonic)
0 the system is at equilibrium and no net change takes
place
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Endergonic and Exergonic processes

Reactant A must lose energy

(exergonic) to be converted to the
product B and the energy lost is
required by reactant C (endergonic)
to be converted to product D

A + C → B + D + Heat
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Endergonic and Exergonic processes
• Common obligatory intermediate (I) : A + C → I → B + D
• AH2 + B → I→ A + BH2

• Rxt Classification:
• Exothermic ( H < 0) or endothermic ( H > 0)- Heat ↕
• Exergonic ( G < 0) or Endergonic ( G > 0) -- free energy ↕
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Exergonic Versus Endergonic reactions
Endergonic Reactions
― Unfavorable or nonspontaneous reaction.
― Requires energy (thus absorb energy from the
surroundings)
― The free energy of the system increases.
― ∆Go is positive >0; ∆S decreases.
― Examples include photosynthesis, melting of ice
into liquid water, evaporating liquid water, Melting
ice
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Exergonic Versus Endergonic reactions
Exergonic Reactions
―Spontaneous or a favorable reaction.
―Release energy to the surroundings.
―The free energy of the system decreases.
―∆Go is negative <0; ∆S increases.
―Examples include mixing sodium and chlorine to
make table salt, combustion, etc

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Exergonic Versus Endergonic reactions AND ∆GO

• A, exergonic spontaneous Rxt; B, endergonic non spontaneous Rxt ; At

equilibrium states, the Gibbs energy of the products is lower than that
of the reactants in A while the opposite will be true for B
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 ATP (Adenosine triphosphate)
• AH2 + B → I→ A + BH2
I

• Most situations : I is not related to ABCD but acts as an

energy transfer from the exergonic pathway of reactions
to endergonic pathway of reactions
• Such is the role of ATP
• Principal high-energy intermediate or carrier compound
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 ATP (Adenosine triphosphate)
• ATP plays a central role in the transference of free
energy from the exergonic (catabolic) to the
endergonic (anabolic) processes.
• Example Body processes include: biosynthesis,
muscular contraction, nervous excitation, and active
transport
• ATP has a high group transfer potential compared to
ADP to AMP (low-energy type)
• ATP acts as the “energy currency” of the cell
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
ATP (Adenosine triphosphate)

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Other high-energy compounds
• Thiol esters involving coenzyme A (eg, acetyl-CoA),

• Acyl carrier protein,

• Amino acid esters involved in protein synthesis,

• S-adenosylmethionine (active methionine),

• Uridine diphosphate glucose (UDPGlc),

• 5-phosphoribosyl-1-pyrophosphate (PRPP).
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 ATP hydrolysis

(Group transfer potential)

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 ATP hydrolysis

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Sources of Phosphate for energy conservation
or energy capture (ATP):
• 1. Oxidative phosphorylation – has the greatest
quantitative source of ∼Phosphate where ATP is
generated in the mitochondrial matrix as O2 is reduced to
H2O by electrons passing down the respiratory chain
• 2. Glycolysis. A net formation of two ∼Phosphates
where formation of lactate from one molecule of glucose,
generated in two reactions catalyzed by phosphoglycerate
kinase and pyruvate kinase, respectively
• 3. The citric acid cycle. One ~phosphate is generated
directly in the cycle at the succinate thiokinase step
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Phosphagens
• Storage forms of group transfer potential
• energy storage compounds (high-energy
phosphate compounds)
• maintain a reserve of high-energy phosphates that can
be used as needed, to provide the energy that could
not be immediately supplied by glycolysis or oxidative
phosphorylation.
• Phosphagens supply immediate but limited energy.

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Phosphagens
• include:
• Creatine phosphate; occurs in vertebrate skeletal muscle,
heart, spermatozoa, and brain.
• arginine phosphate; occurs in invertebrate muscle.

• When ATP is rapidly being utilized as a source of

energy for muscular contraction, phosphagens permit
its concentrations to be maintained, but when the
ATP/ADP ratio is high, their concentration can
increase to act as an energy store

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Clinical significance
• Energy imbalance (Depletion or excess storage of this
energy) results in susceptibility to disease e.g
• Malnutrition, T2DM, CVDs, HTN

• Provides understanding of chemical energy changes in

biochemical reactions required to power living
processes

• Basis for treatment of some conditions

neurodegenerative conditions and cancers
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Redox
Reactions
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Terminologies:
― Oxidation is the removal/loss of electrons (the concept
of break down, exergonic)

― reduction is the gain of electrons (the concept of

anabolism, endergonic)

― In principle oxidation of a molecule (the electron

donor) is always accompanied by reduction of a
second molecule (the electron acceptor).

― Oxidoreductases are enzymes involved in oxidation

and reduction reactions
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Redox principle

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Oxidoreductases
― They catalyze the transfer of electrons from one
molecule (the reductant or electron donor) to
another, (the oxidant or electron acceptor).

― usually utilizes NADP or NAD+ as cofactors

― Classified into four groups namely oxidases,

dehydrogenases, hydroperoxidases, and
oxygenases.

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 1. Oxidases
• catalyze the removal of hydrogen from a substrate
using oxygen as a hydrogen acceptor.
• They form water or hydrogen peroxide as a reaction
product.

• Two types: Flavoprotein and hemoprotein oxidases

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 1. Oxidases
• Cytochrome oxidase
• Is a hemoprotein.
• Has the typical heme prosthetic group
which is present in myoglobin,
hemoglobin, and other cytochromes.
• It is the terminal component of the
chain of respiratory carriers found in
mitochondria and transfers electrons
resulting from the oxidation of
substrate molecules by
dehydrogenases to their final acceptor,
oxygen.

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 1. Oxidases
• Flavoprotein oxidases
• Contain flavin mononucleotide (FMN) or flavin adenine
dinucleotide (FAD) as prosthetic groups;- formed in the body
from the vitamin riboflavin.
• Examples of flavoprotein oxidases include
• L-amino acid oxidase - found in kidney for oxidative deamination of the
naturally occurring L-amino acids;
• xanthine oxidase for conversion of purine bases to uric acid
• aldehyde dehydrogenase, an FAD-linked enzyme present in mammalian
livers, acts on aldehydes and N-heterocyclic substrates.
• The mechanisms of oxidation and reduction of these enzymes are
complex.
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 2. Dehydrogenases
• Two main functions
• Transfer of hydrogen from one substrate to another in a
coupled oxidation–reduction reaction
• Transfer of electrons in the respiratory chain of electron
transport from substrate to oxygen
• Use NAD+ or NADP+—or both (from the vitamin
niacin)
• Found in biosynthetic pathways such as
extramitochondrial pathway of fatty acid synthesis, steroid
synthesis, and the pentose phosphate pathway.
• Other Dehydrogenases Depend on FMN and FAD
• Cytochromes May Also Be Regarded as Dehydrogenases
Except for cytochrome oxidase
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 3. Hydroperoxidases
• use hydrogen peroxide (H2O2)or an organic peroxide
as substrate

• Protect against the harmful effects of reactive oxygen

species (ROS) [ROS contribute to cancer,
atherosclerosis, aging process etc]

• Two types: peroxidases and catalase.

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 3. Hydroperoxidases
• Peroxidases
• Reduce Peroxides Using Various Electron Acceptors such as
ascorbate (vitamin C), quinones, and cytochrome c

• Catalase
• Uses Hydrogen Peroxide as Electron Donor & Electron Acceptor

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 4. Oxygenases
• An oxygenase is any enzyme that oxidizes a substrate
by transferring the oxygen from molecular oxygen O2
(as in air) to it.

• They catalyze the incorporation of oxygen into a

substrate molecule

• Divided into two subgroups, dioxygenases and

monooxygenases.

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 4. Oxygenases
• Dioxygenases Incorporate Both Atoms of Molecular
Oxygen into the Substrate. Examples include the liver
enzymes,
• Homogentisate dioxygenase (oxidase) and 3-
hydroxyanthranilate dioxygenase (oxidase), which contain
iron;

• L-tryptophan dioxygenase (tryptophan pyrrolase), which

utilizes heme.

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 4. Oxygenases
• Monooxygenases (Mixed-Function Oxidases,
Hydroxylases) - incorporate Only One Atom of Molecular
Oxygen into the Substrate
• Cytochromes P450 Are Monooxygenases Important in Steroid
Metabolism & for the Detoxification of Many Drugs
• located mainly in the endoplasmic reticulum in the liver and
intestine, but are also found in the mitochondria in some tissues
• The reactions of P450 enzymes usually results in hydroxylation
• cytochromes P450 and cytochrome b5 are responsible for about
75% of the modification and degradation of drugs, which occurs
in the body.
• Cytochrome b5 is also a fatty acid desaturase.

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Superoxide dismutase protects aerobic organisms
against oxygen toxicity
• is an enzyme that alternately catalyzes the
dismutation (or partitioning) of the
superoxide (O2−) radical into either
ordinary molecular oxygen (O2) or
hydrogen peroxide (H2O2).

• Superoxide is produced as a by-product of

oxygen metabolism and, if not regulated,
causes many types of cell damage.
• By Fvasconcellos (talk · contribs) [Public
domain], via Wikimedia Commons
• https://upload.wikimedia.org/wikipedia/c
ommons/1/13/Superoxide_dismutase_2_
PDB_1VAR.png

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Superoxide dismutase

• The enzyme occurs in all major

aerobic tissues in the
mitochondria and the cytosol.

• Antioxidants, for example, α-

tocopherol (vitamin E), act as
scavengers of free radicals and
reduce the toxicity of oxygen • By Fvasconcellos (talk · contribs) [Public
domain], via Wikimedia Commons
• https://upload.wikimedia.org/wikipedia/c
ommons/1/13/Superoxide_dismutase_2_
PDB_1VAR.png

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Clinical significance
• ATP is generated by oxidative phosphorylation, a series of
redox reactions that involve the presence of oxygen
transforming 1 glucose into 36 ATP molecules, in
presence of oxygen

• Oxidoreductases (e.g cytochrome P450 system) metabolize

many drugs, pollutants, and chemical carcinogens
(xenobiotics) preventing pathology

• Administration of oxygen can be lifesaving in the

treatment of patients with respiratory or circulatory
failure.
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 references
• Botham KM, Mayes PA. Bioenergetics: The Role of ATP.
In: Rodwell VW, Bender DA, Botham KM, Kennelly PJ,
Weil P. eds. Harper's Illustrated Biochemistry, 31e New
York, NY: McGraw-Hill; .
• Botham KM, Mayes PA. Biologic Oxidation. In: Rodwell
VW, Bender DA, Botham KM, Kennelly PJ, Weil P. eds.
Harper's Illustrated Biochemistry, 31e New York, NY:
McGraw-Hill; .
• Nelson DL, Cox MM: Lehninger Principles of
Biochemistry , 6th ed. Macmillan Higher Education, 2013.
• Nicholls DG, Ferguson SJ: Bioenergetics , 4th ed.
Academic Press, 2013.

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm