Mitochondrial respiratory chain Flashcards
How permeable is the outer membrane of the mitochondria?
Freely permeable to small molecules and ions
How permeable is the inner membrane of the mitochondria?
Impermeable to small molecules and ions, including H+
Where is the electron transport chain located?
On the inner mitochondrial membrane
Describe what happens at complex 1
Initially electrons are passed to FMN to produce FMNH2
Subsequently transfer to a series of iron-sulphur clusters
Then transfer to Coenzyme Q, or ubiquinone
So, the enzyme catalyses the overall reaction:
NADH + H+ + Q = NAD+ + QH2
It is a proton pump, moving protons from the matrix into the intramitochondrial space
What is the overall function of complex 1?
Acceptor of electrons from NADH
Moves 4 H+ions from matric to space between the two membranes- proton pump
Describe what happens at complex 2
Succinate is converted to fumarate by succinate dehydrogenase
Electrons of FADH2 pass on their electrons to complex II
Complex II passes them to ubiquinone
How do other substrates for mitochondrial dehydrogenase pass their electrons to ubiquinone?
Straight to ubiquinone
No need for the complexes 1 or 2
Describe the action of complex 3
Ubiquinone: cytochrome c oxidoreductase
Second of three proton pumps in the respiratory chain
Carries 4 H+
Describe the action of complex 4
Cytochrome oxidase
Third and final proton pump- carries 2 H+
Carries electrons from cytochrome c to molecular oxygen
Produces water
Which complex is not a proton pump?
Complex 2
Why is oxygen important for the respiratory electron chain?
Acts as a final electron acceptor
How are the protons pumped?
From energy harnessed from the acceptance of electrons at various points
Conservation of energy- holding energy till the right time to make the ATP
What are the 3 specific systems in the inner mitochondrial membrane that allow movement across the membrane?
Transport ADP and Pi into the matrix
Synthesise ATP
Transport ATP into the cytosol
State the equation for the synthesis of ATP
Give the actual substrates
ADP3- + Pi2- + H+ ——–> ATP4- + H2O
Actual substrates are the Mg2+ complexes of ADP and ATP
Give the number of negative charges of ADP and ATP in the physiological pH range
ATP has 4 negative charges and ADP has 3 negative charges
Describe the Adenine nucleotide translocase
Integral protein of the inner mitochondrial membrane
Transports ADP3- from the intramitochondrial membrane space into the matrix
In exchange for an ATP4- molecule
transported in the other direction
(Favoured by the proton pump)
Known as an ‘antiporter’
Give the name of a specific inhibitor of adenine nucleotide translocase
Atractyloside, a glycoside isolated from a thistle
Describe phosphate translocase
A second membrane transport is essential for oxidative phosphorylation and synthesis of ATP
Transports both phosphate and hydrogen ions into the matrix: a ‘symporter’ - favoured by the transmembrane proton gradient
What is a symporter?
2 things brought in via the same direction
What is an antiporter?
One thing in and one thing out
What are the two functional domains of ATP synthase?
Fo, an oligomycin-sensitive proton channel
F1, an ATP synthase
Describe the subunit structure of F0
Fo comprises three different types of subunit: a, b, and c
Forms a complex of 13-15 subunits
Subunits c1-10 arranged in a circle
Describe the subunit structure of F1
F1 comprises five different types of subunit: alpha3, beta3, gamma, delta, and epsilon
Forms a complex of 9 subunits
What is special about the 3 beta subunits of F1?
The 3 beta subunits have catalytic sites for ATP synthesis
Describe the structure of ATP synthase
- beta subunits are arranged alternately with alpha subunits like segments of an orange
- Form a knob-like structure held by a stalk of the gamma and epsilon subunits
- delta subunit interacts with the two ‘b’
subunits of Fo
Describe the theory of rotational catalysis
3 beta subunits take it in turns catalysing the synthesis of ATP
Any given beta subunit starts in a conformation for binding ADP and Pi
Then changes conformation so the active site now binds the product ATP tightly
Then changes conformation to give the active site a very low affinity for ATP (‘beta-empty’ conformation) so ATP is released
What happens when the gamma unit rotates?
The gamma-unit rotates, and the properties of the beta-catalytic units change
Is the reaction in the respiratory electron chain endergonic or exergonic?
Highly exergonic reaction
Give the overall equation of the respiratory electron chain in terms of NADH
NADH + H+ + ½ O2 ——-> NAD+ + H2O
Describe the energy changes in this reaction
Energy released is coupled to the movement of H+ across the inner membrane
Electrochemical energy generated represents temporary conservation of the energy of electron transfer
Protons flow spontaneously down their electrochemical gradient releasing energy available to do work
Describe uncoupling reagents and their purpose
Normally e- flow and phosphorylation are tightly coupled
Uncouplers dissipate the pH gradient by transporting H+ back into the matrix of the mitochondria so bypassing the ATP synthase
Thus an uncoupler (e.g. DNP) severs the link between e- flow and ATP synthesis, with the energy being released as heat
Can occur naturally e.g. UCP1 (thermogenin) is found in brown adipose tissue and has a specific H+ channel through which the [H+] may be dissipated - energy released as heat
Describe brown adipose tissue
Brown adipose tissue (BAT): Specialized for heat generation High numbers of mitochondria Mitochondria contain thermogenin (UCP-1) Important in new-borns, possible role in obesity/diabetes
What is the energy yield from oxidation of 1 molecule of glucose
30 or 32
Depending on the shuttle G-3 P or malate-aspartate used
What is DNP?
Weak acid that crosses membranes ‘ferrying’ H+ across
Each DNP molecule collects a proton from the IMS and moves through the membrane with it, depositing it in the matrix
Can then return though the membrane to collect another proton
