Mitochondrial respiratory chain Flashcards
Complex I
NADH dehydrogenase
First and largest protein complex in the ETC that acts as a proton pump.
Initially electrons from NADH is passed to FMN to reduce it to FMNH2, as well as to iron-sulfur clusters.
Exergonic transfer:
Receive a hydride ion and a proton from NADH (2 e-).
Transfers it to ubiquinone.
Endergonic transfer:
Energy from electron transfer couples the transfer of 4 protons from the matrix to intermembrane space.
Equation of the reaction NADH dehydrogenase catalyses
NADH + H+ + Q= NAD+ + QH2
Complex II
Succinate dehydrogenase - the only protein of the ETC that does not act as a proton pump.
Also used in the TCA cycle- converts succinate to fumarate.
Complex II receives electrons from FADH2 and passes it to ubiquinone.
Paths of electrons entering the electron-transfer chain
entering Q
- NADH passes electrons to complex I which ultimately passes it to Coenzyme Q.
- FADH2 passes electrons to complex II, which passes it to ubiquinone.
- G-3-P passes electrons to G3P dehydrogenase—> ubiquinone
- Acyl-CoA dehydrogenase transfer electrons from beta oxidation to ETF:Q oxidoreductase—> ubiquinone.
Complex III
Ubiquinone: cytochrome c oxidoreductase
Second proton pump in the ETC- pumps 4 H+
Receives electrons from QH2 and transfers to cytochrome c.
Complex IV
Cytochrome oxidase- final proton pump, pumps 2 H+
Carries electrons from cytochrome c to molecular oxygen to produce water:
1/2O2 + 2H+ = H2O
Adenine nucleotide translocase
Antiporter in the inner mitochondrial membrane that transports:
- ADP3- to the matrix
- ATP4- to the intermembrane space
Due to protons being pumped into the intermembrane space, the electrochemical gradient favours this movement.
Atractyloside
A glycoside that specifically inhibits adenine nucleotide translocase.
Acts as a poison.
Phosphate transolcase
Symporter in the inner mitochondrial membrane.
Transports both H+ and H2PO4- from the intermembrane space to the matrix.
The H2PO4- acts as a source for inorganic phosphate to make ATP.
This movement is supported by the electrochemical gradient created by the proton pumps in the ETC.
ATP synthase
An F-type ATPase with two domains:
F0- proton channel
F1- ATP synthase
This protein drives the synthesis of ATP
F0 domain
An oligomycin sensitive proton channel domain of the ATP synthase.
3 subunits, which a complex of 13-15 further subunits.
Main subunits—> a, b, c
Subunits C1-10 are in a circle and this is the unit that initially rotates.
F1 domain
- Subunits, and their functions
The ATP synthase domain in the f-type ATPase.
5 sub units:
-Alpha-3
-Beta-3: catalytic sites for ATP synthesis
gamma
-Delta- interacts with the 2 b units of F0
-Epsilon
All form a complex of 9 further subunits
Alpha and beta units are arranged alternately and are held by gamma and epsilon subunits.
Rotational catalysis of ATP-synthase
Beta subunits of F1 domain take in turns making ATP by binding ADP and Pi.
- The c-ring of the F0 domain rotates which causes the gamma and and epsilon units to rotate.
- The beta-alpha units are stationary (and ab units of F0).
- Every rotation of the gamma unit changes the catalytic property of the beta-subunit. Gamma unit can only associate with one alpha-beta unit at a time.
- Starts at loose confirmation: ADP and Pi can bind.
- Tight confirmation: active site of beta unit binds to form ATP tightly.
- Beta-empty/ open confirmation:
Beta active site has low affinity for ATP and ATP is released.
Energy changes in ATP synthase
Protons flow down its electrochemical gradient across ATP-synthase.
This is exergonic, and releases energy for ATP synthesis in the F1 domain
Conservation of electron transfer energy
When water is made at complex IV:
NADH + H+ +1/2O2= H2O + NAD+
This reaction is highly exergonic and releases energy for protons to be pumped.
The electrochemical energy generated shows that the energy from electron transfer was temporarily conserved.
Energy yield of glycolysis from one glucose molecule
2 NADH= 3/5 ATP depending on what shuttle was used
2 ATP from making pyruvate.
Energy yield of pyruvate oxidation from one glucose molecule
2 NADH = 5 ATP molecules
Energy yield of the citric acid cycle from one glucose molecule
6 NADH = 15 ATP
2 FADH2= 3 ATP
2 ATP
Uncoupling reagents
Substances that transport H+ back into the mitochondrial matrix from the intermembrane space, without passing through ATP-synthase.
This dissipates the proton gradient and blocks the coupling energy between energy flow and ATP synthesis.
This causes energy to be release as heat instead of ATP.
Examples of uncoupling reagents
DNP
UCP1/ thermogenin in brown adipose tissue.
UCP-1
This protein is a channel found in the mitochondrial inner membrane of brown adipose tissue.
It serves as an uncoupling reagent for ATP synthesis by allowing H+ to bypass ATP-synthase into the matrix.
This causes a lot of heat generation in brown fat (seen in babies, to help regulate heat).
This could also play a role in diabetes and obesity.
DNP
A weak acid that acts as an endogenous uncoupling reagent.
When it crosses the inner mitochondrial membrane, it carries H+ and causes it to bypass ATP-synthase.
Used to be used in slimming pills but found out to have toxic effects like:
Liver damage
Respiratory acidosis
Hyperthermia
