Transcript lec4.Respiratory chain.mac2010-09

Dr. M. Azhar Chishti
Dept. Medical Biochemistry
Objective
1. To correlate between the oxidation of food
molecules by cellular respiration and the
mitochondrial extraction of electrons to produce
ATP
2. To understand that the mitochondrial electron
transport chain provides a mean of using the
reducing potentials to produce ATP.
Lecture outline
1. The oxidation of food molecules by cellular respiration and
the mitochondrial extraction of electrons
2. The components of the electron transport chain and ATP
formation complex located in the inner mitochondrial
membrane
3. The oxidative phosphorylation is a coupling process
between electron transport chain and ATP production
4. Mitochondrial apoptosis: the programmed cell death
5. The uncouplers and their role in thermogenesis.
6. Mutation in mitochondrial DNA and its clinical
application
7. The shuttles giving an example to a shuttle (briefly)
Respiratory Chains
 Energy-rich molecules, such as glucose, are metabolized by a
series of oxidation reactions ultimately yielding ‫بالنهايه تعطي‬
CO2 and water.
 The metabolic intermediates of these reactions donate
electrons to specific coenzymes—
Nicotinamide adenine dinucleotide (NAD+)
and flavin adenine dinucleotide (FAD)—
 These form the energy-rich reduced coenzymes, NADH
and FADH2.
Electron Transport Chain
Electron transport and ATP synthesis are tightly coupled processes
Electron transport chain
These reduced coenzymes can, in turn, each donate a pair of
electrons to a specialized set of electron carriers, collectively
called the electron transport chain.
As electrons are passed down the electron transport chain, they
lose much of their free energy.
Part of this energy can be captured and stored by the production
of ATP from ADP and inorganic phosphate (Pi). This process is
called oxidative phosphorylation
The remainder of the free energy not trapped as ATP is used to
drive ancillary reactions such as Ca2+ transport into
mitochondria, and to generate heat. ‫مفيده لتدفئه الجسم‬
Mitochondria
Outer Membrane: permeable ‫منفذ‬
Inner membrane: impermeable ‫غير منفذ‬
Matrix: 50% protein
Oxidation of pyruvate, Β-oxidation
TCA cycle, Urea synthesis, NAD, FAD
ADP+P=ATP
Mitochondrion
 The electron transport chain is present in the inner mitochondrial
membrane ‫ مهمه‬and is the final common pathway by which electrons
derived from different fuels of the body flow to oxygen.
 Electron transport and ATP synthesis by oxidative phosphorylation
proceed continuously in all tissues that contain mitochondria.
 Structure of the mitochondrion: The components of the electron
transport chain are located in the inner membrane.
 The outer membrane contains special pores, making it freely
permeable to most ions and small molecules.
 The inner mitochondrial membrane is a specialized structure that is
impermeable to most small ions including H+, Na+, and K+, and small
molecules such as ATP, ADP, pyruvate, and other metabolites important
to mitochondrial function .
 Specialized carriers or transport systems are required to move ions or molecules
across this membrane.
 ATP synthase complexes: These complexes of proteins contain domains that span
‫ جسر‬the inner mitochondrial membrane, and domains that appear as spheres that
protrude into the mitochondrial matrix.
 Matrix of the mitochondrion: This gel-like solution in the interior of mitochondria
is 50% percent protein.
 These molecules include the enzymes responsible for the oxidation of pyruvate,
amino acids, fatty acids (by β-oxidation), and those of the tricarboxylic acid (TCA)
cycle.
 The synthesis of glucose, urea, and heme occur partially in the matrix of
mitochondria.
 In addition, the matrix contains NAD+ and FAD (the oxidized forms of the two
coenzymes that are required as hydrogen acceptors) and ADP and Pi, which are used
to produce ATP.
 [Note: The matrix also contains mitochondrial RNA and DNA (mtRNA and
mtDNA) and mitochondrial ribosomes.]
Electron Transport Chain
Organization of the chain
 The inner mitochondrial membrane can be disrupted into
five separate protein complexes, called complexes I, II, III,
IV, and V.
 Complexes I to IV each contain part of the electron
transport chain . Each complex accepts ‫ يتلقى‬or
donates ‫ يرسل‬electrons to relatively mobile electron
carriers, such as coenzyme Q and cytochrome c.
 Each carrier in the electron transport chain can receive
electrons from an electron donor, and can subsequently
donate electrons to the next carrier in the chain.
 The electrons ultimately combine with oxygen and protons
to form water. This requirement for oxygen makes the
electron transport process the respiratory chain, which
accounts for the greatest portion of the body's use of
oxygen.
Components of the Electron Transport
Chain & Organization of the chain
Complex I
NADH dehydrogenase
Complex III
FMN
Fe-S Centers
Cytochrome b&c1
Coenzyme Q
Heme-containing
(porphyrin ring containing
iron
½O2
Succinate dehydrogenase
FAD
Complex II
H2O
Cytochrome c
Cytochrome aa3
Cu ions
Cytochrome oxidase
Complex IV
Mitochondria and apoptosis
‫املوت املنظم للخليه‬
 The process of apoptosis or programmed cell
death may be initiated by the formation of
pores in the outer mitochondrial membrane.
 These pores allow cytochrome c to leave the
intermembrane space and enter the cytosol.
 Once in the cytosol,cytochrome c, in association
with proapoptotic factors, activates a family of
proteolytic enzymes (the caspases), causing
cleavage of key proteins and resulting in the
morphologic and biochemical changes
characteristic of apoptotic cell death
Chemiosmotic Hypothesis
Chemiosmotic Hypothesis
‫الرسمه مهمه وتشرح‬
‫الموضوع‬
‫مهمه جدا‬
catalytic activity
 Proton pump: Electron transport is coupled to
the phosphorylation of ADP by the transport
(“pumping”) of protons (H+) across the inner
mitochondrial membrane from the matrix to the
intermembrane space.
 The energy generated by this proton gradient is
sufficient to drive ATP synthesis.
 The proton gradient serves as the common
intermediate that couples oxidation to
phosphorylation.
 ATP synthase: The enzyme complex ATP synthase
(complex V) synthesizes ATP, using the energy of
the proton gradient generated by the electron
transport chain.
Uncoupling proteins (UCP)
‫مهمه‬
UCP1, also called thermogenin , is
responsible for the activation
of fatty acid oxidation and heat production
in the brown adipocytes of mammals.
Inherited defects in oxidative phosphorylation
 Defects in oxidative phosphorylation are more likely a
result of alterations in mtDNA ‫الدي ان اي الخاص بالميتوكندريا‬,
which has a mutation rate about ten times greater than that
of nuclear DNA.
 Mutations in mtDNA are responsible for several diseases,
including some cases of mitochondrial myopathies and
Leber hereditary optic neuropathy.
 The mtDNA is maternally ‫ قادم من االم‬inherited because
mitochondria from the sperm cell do not enter the
fertilized egg.
Membrane Transport Systems
 The inner mitochondrial membrane is
impermeable ‫ غير منفذ‬to most charged or
hydrophilic substances.
 However, it contains numerous transport proteins
that permit passage of specific molecules from the
cytosol (or more correctly, the intermembrane
space) to the mitochondrial matrix.
CONCLUSION
1. The oxidation of food molecules by cellular respiration.
2. The electron transport chain and ATP formation
3. The oxidative phosphorylation is a coupling process and
uncouplers and their role in thermogenesis.
4. Mitochondrial apoptosis: the programmed cell death and
mutation in mitochondrial DNA and its clinical application
5. The shuttles (briefly)
‫‪THANK YOU‬‬
‫اللي فهم شيء يعلمني ‪‬‬