Electron transport chain Flashcards
what is the electron transport chain
aka respiratory chain
Comprises 4 large multi-unit proteins intrinsic to inner mitochondrial membrane
Catalyse a series of reactions
NADH+H++1/2O2>NAD++H2O
Energy released from reaction by tightly coupled production of ATP
What are the components of ETC
Four components
Complex I, II, III and IV
What proteins are linked to the components of ETC
2 soluble proteins
Ubiquinone (coenzyme Q) – a lipid soluble benzoquinone with a long isoprenoid tail
Cytochrome C
Free to move in membrane by diffusion, not part of complexes
What enzymes are involved in the protein complexes of the ETC
NADH dehydrogenase Succinate dehydrogenase ubiquinone: cytochrome C oxidoreductase cytochrome C (moves between complex III and IV) Cytochrome oxidase
what is complex I
NADH dehydrogenase
what does complex I do
Initially electrons are passed to FMN to produce FMNH2
Subsequently transfer to series of iron-sulphur clusters then transfer to ubiquinone (coenzyme Q)
So enzyme catalyses NADH+H++Q=NAD++QH2
Proton pump, moving protons from matrix to intramitochondrial space
QH2 released outside and NAD+ stays in
4H pass
what is complex II
succinate dehydrogenase
What does complex II do
FAD within complex II is reduced to FADH2 by electrons gained from conversion of succinate to fumarate in TCA cycle
Complex II passes electrons to ubiquinone
Other substrates for mitochondrial dehydrogenases also pass on their electrons to ubiquinone but not through complex II (eg from G3P shuttle)
QH2 released
Sources of electrons entering the ETC
NADH +H+
Succinate to fumarate
FAD
ETF:Q oxidoreductase
what is complex III
Ubiquinone: cytochrome c oxidoreductase
what does complex III do
Accepts electrons from reduced ubiquinone and pass to complex IV via cyt c
2nd of 3 proton pumps in respiratory chain
4H pass
what is complex IV
Cytochrome oxidase
What does complex IV do
3rd and final proton pump
Carries electrons from cytochrome c to molecule oxygen, produces water
2h pass
how is ATP synthesised
Inner mitochondrial leaflet is generally impermeable to charged species but 3 specific systems in the membrane Transport ADP and Pi into matrix Synthesis ATP Transport ATP into cytosol ADP3-+P2-+H+=ATP4-+H2O
How is the adenine nucleotide translocated
Integral protein of inner mitochondrial membrane
transport ADP from intramitochondrial membrane to matrix in exchange for ATP (favoured by electrochemical gradient generated by proton pump)
Known as anti porter
how can adenine nucleotide translocation be inhibited
Atractyloside, a glycoside isolated from a thistle is a specific inhibitor of adenine nucleotide translocase
how is phosphate translocated
A second membrane transporter essential for oxidative phosphorylation and synthesis of ATP
Transports both phosphate and hydrogen ions into matrix, symporter
favoured by transmembrane proton gradient
what synthesises ATP
An F-type ATPase
Two functional domains
1 Fo an oligomycin-sensitive proton channel
2 F1 ATP synthase
What is the structure of ATP synthesis
Fo comprises of three different types of SU a b and c
Forms a complex of 13-15 Sus
Sus c1-10 arranged in a circle
F1 comprises 5 different types of SU a3, B3, y, delta and epsilon
Forms a complex of 9 SU (3B and 3a Sus, have catalytic sites for ATP synthesis)
how are the B SUs of F1 arranged
B Sus are arranged alternately with a SUs like segments of an orange
Form a knob-like structure held by a stalk of y and epsilon Sus
Delta SU interacts with 2 b Sus of Fo
what is the. theory of rotational catalysis
3 B Sus take it in turns catalysing the synthesis of ATP
Any given B SU starts a conformation for binding ADP and Pi
Then changes conformation so active site now binds the product ATP tightly
Then changes conformation to give active site a low affinity for ATP (B-empty conformation) so ATP released
how does the y SU affect the B-catalytic units
The y-SU rotates and the properties of B-catalytic units change
what type of reaction is the reduction of NADH
Highly exergonic reaction
What results from the reduction of NADH
Energy released is coupled to movement of H+ across inner membrane
Electrochemical energy generated represents temporary conservation of energy of e- transfer
Protons flow spontaneously down their electrochemical gradient releasing energy available to do work
what are uncoupling reagents
Normally e- flow and phosphorylation of ADP tightly coupled
Uncouplers dissipate the pH gradient by transporting H+ back into the matrix of mitochondria bypassing the ATP synthase
what is an example of uncoupling agents
An uncoupler (eg DNP ) severs link between e- flow and ATP synthesis with energy released as heat Can occur naturally eg UCPI (thermogenin) is found in brown adipose tissue and has a specific H+ channel through which H+ may be dissipated- energy released as heat
how does uncoupling link to brown fat thermogenesis
BAT – high numbers of mitochondria (contain UCP1)
Extra protein in membrane for protons to bypass ATP synthesis
Specialised for heat generation – important in newborns, important in obesity/diabetes
how is DNP an uncoupler
exogenous uncoupler
Weak acid that crosses membrane ferrying H+
Each DNP molecule collects a proton from IMS and moves through membrane
Can return to collect more
what are the effects of DNP uncoupling
Toxicity arises from liver damage, respiratory acidosis and hyperthermia
