Download Electron transport chain, oxidative phosphorylation

Electron transport chain,
oxidative phosphorylation &
mitochondrial transport systems
Joško Ivica
Electron transport chain & oxidative
phosphorylation
Oxidation of foodstuffs
 collects e- & -H
 oxidizes e- & -H
e- & -H
REDUCING EQUIVALENTS
Oxidative breakdown
of foodstuffs
NAD+
-2 e-
+2 e-
NADH
Fig. taken from http://www.textbookofbacteriology.net/metabolism_2.html
FMN = Flavin mononucleotide
FAD = Flavin adenine dinucleotide
Oxidative breakdown
of foodstuffs
 reduced
coenzymes NADH and FADH2 generated during TCA cycle, fatty acid
oxidation or glycolysis are oxidized by the electron transport chain (respiratory
chain)
Mitochondria
The system of electron carriers of ETC is located in
the inner mitochondrial membrane
OXIDATION-REDUCTION REACTIONS
Aox + Bred
Ared + Box
E‘°= standard oxidation-reduction (redox) potential
Redox system
NAD+ + 2H+ + 2eNADH + H+
Coenzyme Qox + 2e coenzyme Qred
Cytochrome b (Fe3+) + eCytochrome b (Fe2+)
Cytochrome c (Fe3+) + eCytochrome c (Fe2+)
Cytochrome a (Fe3+) + eCytochrome a (Fe2+)
½ O2 + 2H + 2e2H2O
E‘°
-0.32
+0.10
+0.12
+0.22
+0.29
+0.82
ELECTRON TRANSPORT CHAIN
Electrons are transferred from one complex to another in steps
The final acceptor of electrons is a molecule of oxygen (O2)
ELECTRON TRANSPORT CHAIN
Electron carriers (ETC complexes) are arranged in order of increasing redox potential (from the most
Increasing affinity for electrons, which drives
negative to the most positive redox potential)
the flow of electrons in this direction!
During reduction-oxidation reactions energy is released!
Energy released in reduction-oxidation reactions is used for
pumping H+ from matrix into intermembrane space
Higher concentration of H+ in intermembrane space  electrochemical potential gradient or proton
gradient across the inner mitochondrial membrane
Proton gradient provides energy for synthesis of ATP!
protonmotive force = electrochemical potential gradient
ΔpH = 0.75-1 pH units
ΔΨ = 0.15-2.0 V
The energy stored in protonmotive force drives the synthesis
of ATP by the movement of protons down the electrochemical
gradient through the ATP-synthase
Peter Mitchell’s chemiosmotic theory
ELECTRON TRANSFER FROM COMPLEX 1, COMPLEX 2 & OTHER FLAVOPROTEINS
GLYCEROL 3-PHOSPHATE-DEHYDROGENASE
COMPLEX 1
NADH-DEHYDROGENASE
NADH
SUCCINATE-DEHYDROGENASE
FMN = Flavin mononucleotide
ETF = Electron-transferring flavoprotein
β-OXIDATION OF FATTY ACIDS
ACYL-CoA DEHYDROGENASE
UBIQUINONE = COENZYME Q
• Complex 3 (CYTOCHROME b-c1 COMPLEX): Rieske Fe-S protein,
cytochrome b, cytochrome c1
• Complex 4 (CYTOCHROME OXIDASE): Cu, cytochromes a and a3
ATP SYNTHASE
ADP + Pi
ATP
Energy from the proton gradient is used for
the release of the newly synthesized ATP
Oxidative phosphorylation yields most of ATP
produced in cell
ELECTRON TRANSPORT CHAIN PRODUCES THE MAJORITY OF
ENERGY = ATP FROM FUEL OXIDATION
• NADH oxidation (2e-) ……….. 2.5 ATP
• FADH2 oxidation (2e-) ……….. 1.5 ATP
ATP
SUMMARY
-
Electron transfer within inner mitochondrial membrane occurs stepwise
through a series of four complexes and two mobile carriers to the final
acceptor O2
-
As electrons move through complexes 1, 3 and 4, protons are taken up
from the matrix and released on the cytosolic side of the membrane
-
Higher concentration of protons in intermembrane space creates
electrochemical potential gradient or proton gradient (pH in matrix is
higher and it is negatively charged compared to intermembrane space)
-
Proton gradient causes proton reflux into the matrix through ATPsynthase that drives the formation of ATP by causing the release of
bound ATP from the catalytic site
RESPIRATORY CONTROL
Rate of electron transport is tightly coupled to ATP synthesis
NAD+
NAD+
NAD+
Higher ATP consumption ( ADP) leads to
increased rate of electron transport
chain ( NAD+)
ADP, NAD+  increased fuel oxidation
(glycolysis, TCA, fatty acid oxidation)
NAD+
muscle contraction
active transport
biosynthesis
ATP
ADP + Pi
CLINICAL CORRELATION
• Patient experiences a second myocardial infarction confirmed by an
electrocardiogram showing direct evidence of severe ischemia (lack
of blood flow)
• Elevated blood levels of creatine kinase-MB (CK-MB) and troponin I
(TnI)
Ischemia has caused hypoxia (low levels of oxygen) in the heart
muscle, resulting in inadequate generation of ATP (needed for the
activity of Na+/K+ ATP-ase)
This leads to irreversible cell injury (necrosis) and consequently to
leakage of cellular proteins into the bloodstream.
CLINICAL CORRELATION
• Acute inhalation or ingestion of high concentrations of cyanide (CN-),
which is one of the most potent poisons, leads rapidly to convulsions,
coma and death
It binds to the Fe3+ of heme a3 in cytochrome oxidase and prevents electron
transport to O2
Mitochondrial respiration and energy (ATP) production cease leading to cell
death.
Mitochondrial transport systems
glycolysis
Glycolysis
cytosol
Reducing equivalents from NADH produced in
glycolysis are transported into mitochondrion
by shuttle systems
MALATE-ASPARTATE SHUTTLE
GLYCEROL-PHOSPHATE SHUTTLE
AST
AST
Mitochondrion
MDH – malate dehydrogenase
G3PDH – glyceraldehyde 3-phosphate dehydrogenase
AST – aspartate aminotransferase
Cytosolic
glycerol 3-phosphate dehydrogenase
Dihydroxyacetone phosphate
Glycerol 3-phosphate
Mitochondrial
Cytosol
glycerol 3-phosphate dehydrogenase
Inner
mitochondrial
membrane
Mitochondrion
MITOCHONDRIAL TRANSPORTERS
SYMPORT
ATP/ADP TRANSLOCASE
ANTIPORT
MITOCHONDRIAL TRANSPORTERS
UNIPORT
EXPORT OF CITRATE
Mitochondrion
Malate
Citrate
CoASH
Citrate synthase
Acetyl CoA
Oxaloacetate
NONSHIVERING THERMOGENESIS
brain
norepinephrine
SUMMARY
• ETC represents a series of redox reactions where electrons are
eventually passed to the final acceptor – oxygen
• Redox reactions cause H+ pumping from mitochondrial matrix into the
intermembrane space generating protonmotive force
• Reflux of H+ back into the matrix drives ATP synthesis i.e. release of
newly synthesized ATP from the enzyme (ATP synthase)
• ATP generated by oxidative phosphorylation can be used then in
extramitochondrial compartments after being transported by specific
mitochondrial transporter