electron transport chain dr. saidunnisa professor of biochemistry
TRANSCRIPT
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Electron transport Electron transport chainchain
Dr. SaidunnisaProfessor of Biochemistry
Matrix H+
+ NADH NAD+ + 2H+ 2H+
+ ½ O2 H2O 2 e
I Q III IV
Intermembrane Space cyt c
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Learning objectivesLearning objectives At the end of the session the student
shall be able to define, describe, enumerate, analyze and list:
1. Location of ETC2. Components of ETC3. Sites of ATP production4. Oxidative phosphorylation5. Chemiosmotic theory 6. Energetics of ETC
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I. Case:I. Case:A 35-year old male is rescued from
enclosed fire. Upon arrival in the emergency
department, he is disoriented and in moderate distress. He is coughing up soot, and has difficulty breathing.
Initial vital signs: BP 90/60, HR 120, RR 30, O2 sat 95%On examination: burned nasal hair, soot
around mouth, burns to face, arms and back.
What are the immediate concerns?
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1Case conti…1Case conti…We have a tendency to focus on CO
as the diagnosis in victims of smoke inhalation.
Pitfall – CN exposure is frequently
overlooked. Consider that CN can be produced from the combustion of paper, silk, wool, plastic, and cotton.
The probability of CN exposure in fires is therefore high.
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1. Case conti……1. Case conti……Lets us unfold the mystery of CO
and CN poisoning on human health while studying respiratory chain.
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Stages of oxidation of food Stages of oxidation of food stuffsstuffs
First stage: Digestion in the GIT converts the
macro molecules into small units. (carbohydrates into glucose, lipids into fatty acids, proteins into amino acids).
This is called primary metabolism.
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Introduction Introduction
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Second stageSecond stage
These products are absorbed in mitochondrial citric acid cycle to generate reducing equivalents NADH or FADH2.
This is called secondary or intermediary metabolism.
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Third stageThird stage
These reducing equivalents enter into the electron transport chain or respiratory chain where energy is released (ATP).
This is tertiary metabolism or internal or cellular respiration.
The energy (ATP) is then used for body synthetic purpose.
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Cellular RespirationCellular Respiration
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ATP-Universal currency of ATP-Universal currency of energy in living cellsenergy in living cells
The energy released from the hydrolysis of ATP is utilized for
Mechanical -muscle contractionTransport work -Sodium potassium
ATPase pumpBiochemical work -Initial steps of
GlycolysisAnabolic pathways -TAG, DNA, Protein
synthesisDetoxification(urea cycle),formation of
active intermediates like UDP glucose
HEAT
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Chemistry of ATP hydrolysisChemistry of ATP hydrolysisThere are two high energy bonds in ATP
which are represented by a squiggle bond () on hydrolysis each releasing -7.3kcal/ mole.
Any bond that can be hydrolyzed with the release of same energy as ATP hydrolysis is called as “high energy bonds”.
More than 90% of ATP is formed through ETC.
Synthesis of ATP:Oxidative phosphorylationSubstrate level phosphorylation
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High energy compoundsHigh energy compounds
High energy compounds:
ATP, GTP, UTP,PEPCarbamoyl phosphatecAMP 1-3
BisphosphoglycerateCreatine PhosphateAcetyl Co ASAM
Low energy compounds
AMPGlucose-1
phosphateFructose-1-
phosphate
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Redox potentialsRedox potentialsOxidation: loss of
electronsReduction: gain of
electronsRedox couple: when
a substance exists both in the reduced and oxidized state.
Redox potentials: electron transfer potential E0’.
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Substrate level Substrate level phosphorylationphosphorylationEnergy from a high energy
compound is directly transferred to ADP or GDP to form ATP or GTP without the help of electron transport chain.
Examples:1.Bisphosphoglycerate kinase
(glycolysis)2.Pyruvate kinase (glycolysis)3.Succinate thiokinase (TCA cycle)
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Biological oxidationBiological oxidation
Definition: Transfer of electrons from reduced coenzymes through ETC to oxygen.
Energy released during this process is trapped as ATP.
This coupling of oxidation with phosphorylation is called oxidative phosphorylation.
In the body this is carried out by successive steps of dehydrogenations.
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NADNAD+ + Linked Linked dehydrogenases dehydrogenases NAD+ is derived from nicotinic acid a
Vitamin B-complex. When NAD+ accepts the two hydrogen
atoms, one of the hydrogen atom is removed from the substrate as such the other is split into one hydrogen ion and one electron.
The electron is also accepted by the NAD+ so as to neutralize the charge on the co-enzyme.
H2 H + H+ + e-
AH2 + NAD+ A + NADH + H+
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NADNAD+ + Linked Linked dehydrogenases dehydrogenases Examples: 1.Glyceraldehyde -3-phosphate
dehydrogenase.2.Isocitrate dehydrogenase3.Glutamate dehydrogenase4.Pyruvate dehydrogenase5.Alpha ketoglutarate
dehydrogenase
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FADFAD Linked Linked dehydrogenases dehydrogenases FAD is derived from riboflavin a
Vitamin B-complex. Both the hydrogen atoms are
attached to the flavin ring. AH2 + FAD FADH2
Examples:1.Succinate dehydrogenase2.Fatty acyl CoA dehydrogenase.
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Mitochondrial Mitochondrial OrganizationOrganization
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Components of ETCComponents of ETC5 Complexes1. Enzyme complex I, (NADH
dehydrogenase)2. Enzyme complex II (Succinate
dehydrogenase)3. Enzyme complex (III)
Cytochrome reductase 4. Enzyme complex (IV)
Cytochrome oxidase. 5. ATP Synthase (V)
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Components of ETCComponents of ETC
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Two mobile carriers These are connected by two mobile
carriers Coenzyme Q, Cytochrome C.
Coenzyme Q, connects complex-1 and 11.
Cytochrome C connects complex 111 and 1V
Electrons flow from more electronegative to electropositive components.
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Complex-IComplex-I
Complex- IVComplex- IV
Coenzyme Q
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Iron sulfur proteins and Iron sulfur proteins and CytochromesCytochromesIron sulfur proteins: They exist in the
oxidized (Fe+3) or reduced (Fe+2) on accepting an electron.
Cytochromes: Cytochromes: Cytochrome C is a mobile component of ETC.
Iron in cytochromes is alternatively oxidized (Fe+3) and reduced (Fe+2) .
The electrons are transported from coenzyme Q to cytochromes in the order b,c1,c, a and a3 during electron transport.
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Components of ETCComponents of ETC
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Complex-V ATP synthaseComplex-V ATP synthase
Enzyme that generates ATP sometimes referred as complex-V.
It has two functional subunits Fo (oha) and F1 portion
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Chemi-osmotic theoryChemi-osmotic theoryThe proton pumps (complexes -I, III,
IV) expels H+ from inside to outside of the membrane.
So there is high H+ concentration outside .
This causes H+ to enter into mitochondria through the channels (Fo –F1complex ) , this proton influx binds to oxygen of pi+ADP to form ATP
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Chemi-osmotic theoryChemi-osmotic theory
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Around 3 protons are required per ATP synthesized.
When 1 NADH transfers its electrons to oxygen, 10 protons are pumped out this accounts for approximately 3 ATP synthesis.
Oxidation of 1 FADH2 is accompanied by the pumping of 6 protons accounting for 2 molecules of ATP.
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Sites of ATP synthesisSites of ATP synthesis
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Oxidative PhosphorylationOxidative Phosphorylation
The process of synthesizing ATP from ADP and Pi coupled with the electron transport chain is known as oxidative phosphorylation.
The complex V of the IMM is the site of O.P
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Inhibitors of oxidative Inhibitors of oxidative phosphorylationphosphorylation1. Oligomycin: an antibiotic, used
as anti-fungal drug, prevents the cell from using the established H+-gradient, to make ATP.
2. Atractyloside: Plant toxin
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Inhibitors of ETCInhibitors of ETCThe inhibitors bind to one of the
components of ETC and block the transport of electrons.
This causes the accumulation of reduced components before the blockade step and oxidized components after that step.
The synthesis of ATP is dependent on ETC.
Hence, all the site specific inhibitors of ETC also inhibit ATP formation.
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Inhibitors of ETCInhibitors of ETC
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Site- of inhibitorsSite- of inhibitors Site –I Between
complex-I and Co-Q:
1. Rotenone : a fish poison
2. Amytal : a barbiturate drug
3. Piercidin A: antibiotic
Site-II cytochrome Cytochrome reductase (b and c1):
1. Antimycin A : antibiotic
2. BAL (British antilewisite): an antidote used against war-gas
Site-III At complex-IV ( cytochrome oxidase):1. Carbon monoxide2. Cyanide3. Hydrogen Sulfide
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UncouplersUncouplers
Compounds that can uncouple or delink the
electron transport chain from oxidative phosphorylation, such compounds are
known as Uncouplers.
The result is that ATP synthesis does not occur.
The energy linked with the transport of electrons is dissipated as heat.
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Chemical UncouplersChemical Uncouplers1. 2,4-dinitrophenol
( has been extensively studied).
2. Dinitrocresol.3. Pentachlorophenol.4. Tri fluoro carbonyl
cyanide phenyl hydra zone (FCCP).
5. Aspirin (high doses).
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Physiological UncouplersPhysiological Uncouplers
1. Thyroxine.2. Long chain fatty acids.3. Unconjugated Bilirubin. These act as Uncouplers only at
high concentration.
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Significance of UncouplingSignificance of Uncoupling Brown adipose tissue
present in the upper back and neck portions and around kidney is rich in mitochondria and carry oxidation uncoupled from phosphorylation.
This causes liberation of heat when fat is oxidized in this tissue.
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Significance of UncouplingSignificance of Uncoupling Examples :
1. New born infant, (Non-shivering Thermogenesis)
2. Hibernating animals
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Brown adipose tissue is located in the neck area and is more physiologically active in the woman than in the man.
1. In certain individuals due to presence of this brown adipose tissue it is believed to protect them from becoming obese.
2. The excess calories consumed by this people are burnt and liberated as heat , instead of being stored as fat.
However, research, that was published in the New England Journal of Medicine, is showing that brown adipose tissue helps adults burn more calories than white adipose tissue.
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Diseases associated with Diseases associated with oxida . phosoxida . phosLHON : Lebers hereditary optic
neuropathyMELAS: Mitochondrial
encephalopathy Lactic Acidosis Stroke
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Learning check Learning check Mr. X 26yrs old male noted heat
intolerance, with profuse sweating . He is loosing weight in spite of good appetite . On physical Examination thyroid swelling was present and T3 and T4 are increased. Give biochemical explanation for above symptoms.