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ETC + Oxidative Phosphorylation - Coggle Diagram
ETC + Oxidative Phosphorylation
Principle of oxidative phosphorylation
NADH + FADH\(_2\) contain energy obtained from catabolism
Electrons release energy as they move along ETC
Energy from e- is used to produce ATP from ADP + P\(_i\)
ETC
Free energy
ATP synthesis
Final electron acceptor is oxygen
Producing water
How is energy released from ETC?
Series of redox pairs
Each with its own redox potential
E\(_0\)
Tendency of a molecule to give up or donate electrons to or from an electrode
In standard conditions
Tendency to donate electrons
Reducing agent
Tendency to accept electrons
Oxidising agent
OIL RIG
Acceptor must have a more positive redox potential than the donor
\(\Delta\)G = -nF\(\Delta\)E\(_0\)
n = no. of electrons
F = Faraday constant
96.4kJ/V
\(\Delta\)E\(_0\) = \(E_{0electronacceptor} - E_{0electrondonor}\)
Overall reaction of ETC
\(_{1/2}\)O\(_2\) + NADH + H\(^+\) = H\(_2\)O + NAD\(^+\)
Electron carriers
First electron carrier is NAD\(^+\)
Flavoproteins
FMN
Intermediate radical
FAD
No +ve charge
Isoalloxazine structure
Dehydrogenases
Part of complex I
Non-haem iron
Iron sulphur (Fe-S) complex
4 types
Based on no of atoms present
Bound to protein via 4 cysteines
Fe-S only found in bacteria
Quinone
Coenzyme Q/ubiquinone/Q\(_{10}\)
Receives 2 electrons + 2 protons
Quinone reduced to hydroquinone
Link between I or II and III
Shuttles proteinsfrom matrix to intermembrane space
Cytochromes (with haem groups)
Haem as prosthetic group
Iron in haem is single-electron carrier
ETC contains several types
Look at slides - not essential
Characterised by absorbance spectra
Energetics of ETC
Redox couples
1/2O\(_2\) + 2H\(^+\) + 2e- = H\(_2\)O
E\(_0\) = 0.82V
NAD\(^+\) + H\(^+\) + 2e- = NADH
E\(_0\) = -0.32V
\(\Delta\)E\(_0\) = 0.82 -(-0.32) = 1.14V
\(\Delta\)G\(^0\) = -2 x 96.4 x 1.14= -220.9kJ/mol
Energy not used to produce ATP
Generate heat
Transport of anions and calcium across inner membrane
P/O ratio of NADH
2.5
P/O ratio FADH\(_2\)
1.5
Glucose + 6O\(_2\) + 30ADP + 30P\(_i\)
6CO\(_2\) + 6H\(_2\)O + 30ATP
Via glycerol phosphate shuffle
Electron transport chain (ETC)
4 large protein complexes (I -IV) + 2 small, mobile carriers
Complexes I,III + IV directly pump proteins from matrix into intermembrane space
Complex II promotes proton pumping in complexes III + IV
Cytochrome C transfers electrons from III to IV
Complex I + II to not communicate with each other
They both transfer electrons to coenzyme Q
Complex I
NADH dehydrogenase/NADH-coQ reductase
Complex II
Succinate dehydrogenase/succinate-coQ reductase
Complex III
Ubiquinol-cytochrome c reductase/CoQ-cytochrome c reductase
Complex III transfers electrons to cytochrome C
Complex IV
Cytochrome oxidase
Each complex contains various cofactors/coenzymes
Required for transfer of electrons to next complex in chain
Complexes
Complex I
Function
Oxidise NADH + reduce CoQ
Large, membrane-spanning complex
Contains binding sites for CoQ + NADH
6-7 Fe-S clusters
Through which e- are carried
In a zig-zag pattern
Transferred to CoQ
Net movement of H\(^+\) occurs
Energy for ATP synthesis
FMN
Complex II
Function
Oxidise succinate via generation of FADH\(_2\)
FADH\(_2\) then reduces CoQ
Energy
Exergonic
Not enough energy to pump H\(^+\) across membrane
Does not span membrane
Binding sites for succinate + CoA
Complex III
Function
Oxidation of CoQ
Reduction of cytochrome C
Large, membrane-spanning complex
Binding sites for CoQ and cytochrome c
Contains cytochrome b + cytochrome c\(_1\)
Rieske Fe-S protein
His not Cys
Complex IV
Function
Oxidise cytochrome c
Reduce oxygen to water
Large, membrane-spanning complex
Binding sites for cytochrome c and molecular oxygen
Bound copper facilitates collection of 4e- needed to reduce O\(_2\)
4e- + O\(_2\) + 4H\(^+\) = 2H\(_2\)O
Q cycle
Transfer of 2e- from CoQ to cytochrome C\(_1\)
Composed of 2 loops
Results in pumping of 4H\(^+\) across the membrane
2 to cytochrome c, leaving semiquinone (semiQ)
2e- transferred to cyt b
From cyt b to Q to form QH\(_2\)
2 more from matrix
ETC inhibitors
Absence of oxygen/anoxia
No terminal acceptor
Iron deficiency/anaemia
No iron for cytochromes or Fe-S
Carbon monoxide
Inhibits complex IV
Mitochondrial shuttles
NADH - NAD\(^+\) is essential for metabolism
Anaerobic conditions
NAD\(^+\) produced by converting pyruvate to lactate
Pyruvate
Lactate
2NADH + H\(^+\)
2NAD\(^+\)
Aerobic conditions
NAD\(^+\) produced by ETC
NADH in cytosol cannot pass directly into mitochondria
Regenerated through mitochondrial shuffles
Glycerol-3-phosphate shuttle
Major shuttle in most tissues
ATP yield = 1.5
NADH in cytosol transfers electrons to dihydroxyacetone phosphate
Forms G3P
G3P transfers electrons to FAD in inner mitochondrial membrane
Forms FADH\(_2\)
Passes electrons through ETC to CoQ
Aspartate-malate shuttle
Used primarily in heart + liver
ATP yield = 2.5
In cytosol NADH reoxidised to NAD\(^+\)
Oxaloacetate forms malate
Malate translocated in exchange to matrix by malate-\(\alpha\)-ketoglutarate carrier
In matrix NAD\(^+\) reduced to NADH
Malate oxidised to oxaloacetate
Oxaloacetate transformed to aspartate
Aspartate aminotransferase
1 more item...
Aspartate in cytosol loses amino acid to form oxaloacetate
1 more item...
Malate dehydrogenase
Transfer electrons through ETC
Under action of malate dehydrogenase
Facilitated by translocation of \(\alpha\)-ketoglutarate in exchange for malate
And
\(\alpha\)-ketoglutarate reacts to form more glutamate
Translocation of glutamate in exchange for aspartate
Oxidative phosphorylation
Chemiosmotic mechanism
Assumptions
Inner membrane impermeable to protons
Protons can only cross inner membrane via carriers of ETC or ATP synthase
Carriers of ETC are vectorially arranged so protons move from matrix to intermembrane space
ATP synthase vectorially arranged in opposite direction to carriers
Electrochemical potential gradient
Complex I
4 protons
Complex III
4 protons
Complex IV
2 protons
pH difference across membrane
0.75
Net movement of charge
Electrochemical potential (ECP)
ECP and H\(^+\) gradient generate force that wishes to establish an equilibrium
Proton motive force
Transfer of protons
2 mechanisms
Redox loop mechanism
Based on no. protons bound in various states
Q cycle + QH\(_2\)
Complex III
Proton pump
Based on conformational change in electron carrier
Complex I + IV
ATP synthase/F\(_0\)F\(_1\) ATPase
Mitchell's chemiosmotic theory
The energy of proton motive force is used by ATP synthase to produce ATP
Re-entry of protons into matrix is facilitated by F\(_0\) subunit of ATP synthase which forms a pore through the inner membrane
Relieves pH and ECP across the membrane
Energy released is used by F\(_1\) subunit to drive synthesis of ATP from ADP + P\(_i\)
Mechanisms of ATP synthesis
F\(_0\) subunit
Composed of
12 c subunits
a subunit
\(\varepsilon\) subunit
a and c combine to form proton channel
F\(_1\) subunit
Composed of
3\(\alpha\beta\) subunits
\(\gamma\) subunit
Acts as rotor triggered by flow of protons through the channel
\(\beta\) subunits contain catalytic site for ATP synthesis
Proton-driven motor/rotary catalysis
12 c subunits
12 protons per turn
3 ATP synthesised per turn
Conserved enzyme complex from yeast to humans
Inhibition of ATP synthesis
Oligomycin antibiotic
Binds to F\(_0\) unit
Inhibits re-entry of protons into matrix
Closes proton channel
Prevents phosphorylation of ADP to ATP
Prevents dissipation of pH gradient + ECP
Highlights tight coupling of electron transport + generation of ATP
Respiratory control
Availability of oxygen has effect on ETC
Mechanism by which [ADP] controls rates of oxidation + phosphorylation
Therefore amount of oxygen consumed
Study of isolated mitochondria in an oxygen electrode
As mitochondria functions electrode detects change in [oxygen]
ADP added causes increase in rate of oxygen consumption
When ADP is used up the rate of oxygen consumption decreases
When oxygen becomes limiting factor rate slows again
Dependent on requirement for ADP + P\(_i\)
Low [ADP]
Low oxygen consumption
Resting state
High [ADP]
High oxygen consumption
Activity/exercise
Uncoupling of oxidative phosphorylation
Protons re-enter matrix without going through ATP synthase
Caused by
Chemicals
Proton ionophores
Form pores to ions to equalise electrochemical gradient
i.e. K+ channels
Physiologically uncoupling proteins
Form channels through inner membrane which conduct protons back into matrix
UCPs
5 isoforms
In brown adipose tissue UCP1
Nonshivering thermogenesis
High in newborns + hibernating animals
Cold survival
Levels associated with obesity
Increased oxygen consumption
Energy released as heat instead of ATP synthesis
ATP/ADP transport
ATP/ADP/P\(_i\) transported through outer membrane via voltage dependent anion channels (VDAC's)
Non-specific pores
Transport through inner membrane is active process
P\(_i\) transported with H\(^+\) via a symport
ATP/ADP transported via antiport system
ATP out ADP in
Termed ANT - adenine nucleotide translocase
Aided by ECP
4 -ve charges out, 3 in
Inhibitors
Plant toxins
Atractyloside + mold toxin
Bongkrekic acid strongly inhibits ANT
Diseases associated with mitochondrial (Mt) DNA
Proteins for mitochondrial function encoded by nuclear + Mt DNA
Mutatin rate of Mt genome
10x nuclear genome
Most effected tissues
High energy requirements
CNS
Skeletal muscle
Heart
Kidney
Lung
Leber hereditary optic neuropathy
Caused by mutation in NADH dehydrogenase (Complex I)