Basics of bioenergetics

2. Definition
 Bioenergetics or biochemical thermodynamics is the
study of energy changes accompanying
biochemical reactions or in biological system.

3. THERMODYNAMICS
 In simple terms, thermodynamics deals with the transfer of
energy from one form to another.
→ The laws of thermodynamics are:
 First law of thermodynamics: Energy can neither be created
nor be destroyed, it can only be transferred from one form to
another.
 Second law of thermodynamics: The entropy of any isolated
system always increases.
 Third law of thermodynamics: The entropy of a system
approaches a constant value as the temperature approaches
absolute zero.
 Zeroth law of thermodynamics: If two thermodynamic
systems are in thermal equilibrium with a third system
separately are in thermal equilibrium with each other.

5.  Entropy is the measure of the number of possible
arrangements the atoms in a system can have.
 Enthalpy is the measurement of energy in a
thermodynamic system.
 Useful Energy = Change in Enthalpy – Change in
Entropy

6. Types of Reactions
ENDERGONIC RECATIONS
 Endergonic reactions may also be called an
unfavorable reaction or nonspontaneous
reaction. The reaction requires more energy than
you get from it.
 Endergonic reactions absorb energy from their
surroundings.

7. Types of Reactions
EXERGONIC REACTIONS
 An exergonic reaction may be called a spontaneous
reaction or a favorable reaction.
 Exergonic reactions release energy to the
surroundings.

8. Types of Reactions

9. Energy Currency of the Cell
Adenosine 5'-triphosphate, or ATP, is the principal
molecule for storing and transferring energy in cells.
It is often referred to as the energy currency of
the cell and can be compared to storing money in a
bank.

10. High Energy Phosphates P
 The phosphate compounds whose ∆G values higher
than that of ATP, they are called High Energy
Phosphates.
 E.g. Phosphoenol Puyruvate , Creatine Phosphate.
 The phosphate compounds whose ∆G values lower
than that of ATP, they are called Low Energy
Phosphates.
 e.g. ADP, Glucose-1-Phosphate.

11. Phosphagens
 Storage forms of high energy phosphates.
 E.g. Creatine Phosphate in vertebrate muscle.
Arginine Phosphate in invertebrate muscle.
Creatine + ATP ⇌ creatine phosphate + ADP (this
reaction is Mg++-dependent)

12. Adenylate kinase
 Adenylate kinase
 K/A myokinase
 Is a phosphotransferase enzyme
 Catalyzes the interconversion of the various
adenosine phosphates (ATP, ADP, and AMP).
 By constantly monitoring phosphate nucleotide
levels inside the cell, ADK plays an important role in
cellular energy homeostasis.

13. Nucleoside-diphosphate kinases
 Nucleoside-diphosphate kinases (NDPKs,
also NDP kinase, (poly)nucleotide
kinases and nucleoside diphosphokinases)
 Are enzymes that catalyze the exchange of terminal
phosphate between different nucleoside
diphosphates (NDP) and triphosphates (NTP) in a
reversible manner to produce nucleotide
triphosphates.

14. Redox Reactions
 An oxidation-reduction (redox) reaction is a type of
chemical reaction that involves a transfer of
electrons between two species.
 Any chemical reaction in which the oxidation number
of a molecule, atom, or ion changes by gaining or
losing an electron.
 Redox reactions are common and vital to some of
the basic functions of life, including photosynthesis,
respiration, combustion, and corrosion or rusting.

15. Oxidative Phosphorylation
 Oxidative phosphorylation is the process in which
ATP is formed as a result of the transfer of electrons
from NADH or FADH 2 to O 2 by a series of electron
carriers.
 This process, which takes place in mitochondria, is
the major source of ATP in aerobic organisms.
 For example, oxidative phosphorylation generates
26 of the 30 molecules of ATP that are formed when
glucose is completely oxidized to CO2 and H2O.

16. Essence of Oxidative Phosphorylation

17. Oxidative Phosphorylation
 Oxidative phosphorylation is the culmination of a
series of energy transformations that are
called cellular respiration or simply respiration in their
entirety.
 First, carbon fuels are oxidized in the citric acid
cycle to yield electrons with high transfer potential.
 Then, this electron-motive force is converted into a
proton-motive force and, finally, the proton-motive
force is converted into phosphoryl transfer potential.

18. RESPIRTAORY CHAIN
Electron Transport Chain in Mitochondria:
A complex could be defined as a structure that comprises a weak protein, molecule or atom that is
weakly connected to a protein.
The plasma membrane of prokaryotes comprises multi copies of the electron transport chain.
 Complex 1- NADH-Q oxidoreductase: It comprises enzymes consisting of iron-sulfur and FMN.
Here two electrons are carried out to the first complex aboard NADH. FMN is derived from vitamin
B2.
 Q and Complex 2- Succinate-Q reductase: FADH2 that is not passed through complex 1 is
received directly from complex 2. The first and the second complexes are connected to a third
complex through compound ubiquinone (Q). The Q molecule is soluble in water and moves freely
in the hydrophobic core of the membrane. In this phase, an electron is delivered directly to the
electron protein chain. The number of ATP obtained at this stage is directly proportional to the
number of protons that are pumped across the inner membrane of the mitochondria.
 Complex 3- Cytochrome c reductase: The third complex is comprised of Fe-S protein,
Cytochrome b, and Cytochrome c proteins. Cytochrome proteins consist of the heme group.
Complex 3 is responsible for pumping protons across the membrane. It also passes electrons to
the cytochrome c where it is transported to the 4th complex of enzymes and proteins. Here, Q is
the electron donor and Cytochrome C is the electron acceptor.
 Complex 4- Cytochrome c oxidase: The 4th complex is comprised of cytochrome c, a and a3.
There are two heme groups where each of them is present in cytochromes c and a3. The
cytochromes are responsible for holding oxygen molecule between copper and iron until the
oxygen content is reduced completely. In this phase, the reduced oxygen picks two hydrogen ions
from the surrounding environment to make water.

19. Electron Transport Chain

20. Chemiosmotic Hypothesis
 In 1961, Peter Mitchell postulated the
Chemiosmotic hypothesis.
 It explains the mechanism of ATP synthesis within
chloroplast during photosynthesis.
 During the photochemical phase or light reaction,
ATP and NADP are generated.
 These are the key components and used in the dark
reaction for the production of the final product of
photosynthesis i.e. sugar molecules.

21. Chemiosmotic Hypothesis

22. THEORY
 According to this theory, molecules like glucose are metabolized to
develop acetyl CoA in the form of an intermediate that is energy-rich.
 The proper oxidation of acetyl CoA occurs in the mitochondrial matrix
and is combined to the reduced form of a carrier molecule namely
FAD and NAD.
 The carriers then supply electrons to the transport chain of the
electron in the inner membrane of mitochondria, which further supply
them to different other proteins present in the ETC.
 The energy present in the electrons is basically used to pump out
protons from the matrix in the inner mitochondrial membrane. It is
used for energy storage in the form of a transmembrane
electrochemical gradient.
 The protons return to the inner membrane by the ATP enzyme
synthase. The proton-flow travels into the matrix of mitochondria
through ATP synthase, which gets a good amount of energy for the
ADP to integrate with inorganic phosphate to produce ATP.

23. ATP SYNTHASE
 F1 (ATPase) is the spherical protein extending into the
matrix.
 Contains 5 different subunits and the catalytic site for
ATP synthesis.
 the complex contains sites that change in their affinity for
ATP as protons flow through the complex.
 This proton flow allows the ATPase to reverse direction
and synthesize ATP.
 F0 is the integral oligomer attached to F1 via a stalk.
 The F0 contains the proton channel.
 The stalk regulates proton flow and ATP synthesis,
contains an F1 inhibitor and is the oligomycin sensitive
region.

24. f0-f1/ATP SYNTHASE

25. Inhibitors of Electron Transport:
 1. Rotenone: inhibits complex I, rat poison and
insecticide.
 2. Antimycin A: an antibiotic which blocks complex
III.
 3. Cyanide: inhibits terminal electron transfer to
oxygen, Complex IV.
 4. Carbon Monoxide: inhibits cytochrome oxidase
by competing with an oxygen- binding site, Complex
IV.

26. Uncouplers / Respiratory Control
 Uncouplers: bind protons, are hydrophobic and can dissipate a pH gradient by
equilibrating H+ (protons).
 i.e. Dinitrophenol (DNP), causes ATP formation to cease but oxygen consumption
remains rapid in an attempt by the mitochondria to maintain the proton gradient.
 Energy is released as heat and body temperature rises.
 Rapid O2 consumption in uncoupling is due to loss of respiratory control.
 Respiratory Control:
 1.Depends on ADP and Pi regulating O2use.
 2. When ATP is high, ADP is limited and O2 use diminishes.
 3. O2 use increases as ATP needs rise.
 4. With uncoupling and no ATP synthesis, the reduction of O2 vis the respiratory chain
is no longer linked to ATP synthesis ------> use is unchecked.
 5. The rate of electron flow is primarily regulated by the ATP:ADP ratio and with
uncoupling this control is lost.
 6. Because respiration remains rapid the cirtic acid cycle and PDH complex continue
at a rapid rate as NADH is maximally oxidized.

27. P / O Ratio:
 The P / O (phosphate:oxygen) ratio represents the
amount of Pi used (ATP synthesized) per atom of
oxygen consumed.
 1. Electron flow from NADH to O2 pumps protons ar
three sites to yield 3 ATP (P / O = 3)
 2. Succinate (via FADH2) bypasses site 1 giving 2
ATP (P / O = 2)
 3. Uncoupling: P / O = 0, oxygen is consumed with
no ATP production.

28. SUBSTRATE LEVEL PHOSPHORYLATION
 Substrate-level phosphorylation refers to the
formation of ATP within certain steps of metabolic
pathway that is, without passing through ETC.
 E.g: Puyruvate kinase, succinate thiokinase.

29. Shuttles
Malate-Aspartate
Shuttle: NADH enters at Complex
I producing 3 ATP.
Glycerol Phosphate
Shuttle: converts NADH to
FADH2 in the cytosol then the
FADH2 enters the chain at
Complex II producing 2 ATP.

30. Mitochondrial Disorders
 Mitochondrial myopathy
 Diabetes mellitus and deafness Diabetes mellitus
 Leber's hereditary optic neuropathy (LHON)
 visual loss beginning in young adulthood
 eye disorder characterized by progressive loss of central vision due to degeneration of the
optic nerves and retina
 affects 1 in 50,000 people in Finland
 Leigh syndrome, subacute sclerosing encephalopathy
 after normal development the disease usually begins late in the first year of life, although
onset may occur in adulthood
 a rapid decline in function occurs and is marked by seizures, altered states of
consciousness, dementia, ventilatory failure
 Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)
 progressive symptoms as described in the acronym
 dementia
 Myoneurogenic gastrointestinal encephalopathy (MNGIE)
 gastrointestinal pseudo-obstruction
 neuropathy

31. Submitted to:
Dr. Sreedevi
MKU
Submitted By
Amreen Khan