Electron Transport Chain Flashcards
TCA Cycle and cancer:
The loss of ____ _____ prevents the repair of double stranded DNA breaks, and the cell accumulates mutations. ____ is the substrate to FH. ____ accumulates and acts as a oncometabolite by blocking HIF Prolyl hydroxylase and other alpha-ketoglutarate dependent dioxygenases
Fumarate hydratase (FH)
Fumarate
Fumarate
The electron transport chain conveys electrons from ___ and ____ to molecular oxygen to make water. The energy from this electron transfer is used to create a ___ ____ across the inner mitochondrial membrane. _____ ____ uses the energy of this proton gradient to add inorganic phosphate to ____, creating ATP.
NADH and FAD2H
Proton gradient
ATP synthase
ADP
ATP synthase allows protons to come back into the ___ ____ powering ATP synthesis
Mitochondrial matrix
When the electron chain reduces NADH, the electrons are Carried from complex I through _____ __ to complex III, then through ____ __ to complex IV.
Coenzyme Q
cytochrome C
Complex ____ reduces molecular oxygen to water
IV
When NADH is used, ____ protons are pumped from the matrix to the intermembrane space, creating the ____ ___
10
Proton gradient
When FAD2H is used, complex ___ performs the oxidation, not Complex I for NADH. Other than that difference, the path is the same
II
When FAD2H is used, ___ protons are pumped across the inner mitochondrial membrane
6
Complex II uses ____ ____ to oxidize FAD2H
Succinate dehydrogenase
Complex I uses ___ ___ to oxidize NADH to NAD+
NADH dehydrogenase
Acyl CoA dehydrogenase in Fatty acid beta-oxidation and glycerol 3 phosphate dehydrogenase can also use ____ and transfer electrons to ____ __
FAD
coenzyme Q
Complex I pumps ___ protons to the intermembrane space
4
Coenzyme Q is lipid soluble and exists in the inner mitochondrial membrane. It can except one electron to form ____ which is its half reduced form, and is the main source of oxidative stress.! it’s fully reduced form is ____.
Semiquinone
Dihydroquinol
Reduced Coenzyme Q (QH2) drops ___ protons off in the intermembrane space as it is oxidized by _____. Then electrons pass directly to ____ through iron-sulfur protein subunits
2
Complex III
Cytochrome C
The oxidation of NADH and the reduction of O2 through complexes I, III, and IV pump ___ protons to the intermembrane space
10
Complex IV uses ____ ___ to oxidize 2 protons and 1/2 O2 to form water
Cytochrome oxidase
The 6th step of TCA cycle using ___ ___ to oxidize Succinate to Fumarate is part of the ____ ___ ___ in Complex II, involved in creating the proton gradient
Succinate dehydrogenase
Electron transport chain
Because complex II (Succinate dehydrogenase) does not span the ___ ___ ___, no protons are pumped into the intermembrane space when it transfers electrons to Coenzyme Q
Inner mitochondrial membrane
Incomplete reduction of oxygen forms ___ ___. Semiquinone interacts with O2, transferring a single electron and forming _____.
Free radicals
Superoxide (O2-)
The ___ ___ is a form of oxidative stress
Hydroxyl radical
According to the ____ ____ of ATP synthesis, the pumping of protons across the mitochondrial membrane generates a proton motive force
Chemiosmotic theory
Protons flow through 12 ___ ____ in the F0 portion of ATP synthase. This rotates the ___ portion which catalyzes ___ synthesis
C subunits
F1
ATP
Translocation of 12 protons completes one ____ of the rotor, generating ___ ATP
Turn
3
There are 3 ____ pairs which are catalytic sites in F1
Alpha-beta
F1 catalytic sites join ADP with inorganic ____ to create ATP
Phosphate
10 protons pumped by NADH
4 protons per ATP
10/4 = _____ ATP per 1 NADH
2.5
6 protons per FAD2H
4 protons per ATP
6/4 = ____ ATP per 1 FAD2H
1.5
A lot of energy is released during the electron transport chain as ___
Heat
_____ and ____ are drugs that chemically uncouples oxidative phosphorylation
Dinitrophenol
Salicylate
____ and ____ are drugs that block Complex I (NADH dehydrogenase)
Rotenone
Amytal
____ is a drug that blocks complex II (Succinate dehydrogenase)
Malonate
______ is a drug that blocks complex III
Antimycin A (antibiotic)
____, ____, and ____ are drugs that block complex IV (cytochrome C oxidase)
Cyanide, carbon monoxide, and Azide
_____ is a drug that blocks ATP synthase (complex V)
Oligomycin (antibiotic)
Summary of drug effects on electron transport chain:
Disrupting the electrochemical potential without synthesizing ATP ____ the electron transport chain. Normally the rate of electron transport chain is tightly coupled to the rate of ATP synthesis
Uncouples
____ ____ is a normal response to cold in infants where they uncouple the electron transport chain from ATP synthase in order to create heat because they can’t shiver
Adaptive thermogenesis
_____ uncoupling is when toxins can transport protons from the intermembrane space to the matrix. This is unregulated and bad
Chemical
____ uncoupling is when damage to membranes equalizes proton concentration between the intermembrane space and matrix. This is unregulated and bad
Mechanical
_____ is a proton channel called thermogenin. It is activated by norepinephrine which allows fat to be utilized for heat, independently of ATP consumption
UCP1
______ is a chemical uncoupler. It is a lipid soluble molecule with a pKa near neutral. Therefore it can bind a proton and diffuse across the inner membrane releasing the proton in the ____
Dinitrophenol
Matrix
Mechanical uncoupling due to peroxidation of ____ lipids by reactive oxygen species. The mitochondria will swell due to an influx of water. Proton leaking makes it impossible to generate the ____ ____
Membrane
Concentration gradient
In healthy cells, the ATP synthase inhibitor ____ causes a decrease in the oxygen consumption rate by ______ (cytochrome C oxidase). The addition of uncoupler ___ restores oxygen consumption
Oligomycin
Complex IV
FCCP
Addition of the complex I inhibitor ____ and the complex III inhibitor ____, deprives cytochrome C oxidase (complex IV) of substrate and causes ____ in oxygen consumption rate
Rotenone
Antimycin A
Decrease
The inner mitochondrial membrane is only permeable to:
O2, CO2, NH3, and H2O
The matrix side is ____ charged compared to the intermembrane space side. The pH is ____ in the matrix than in the intermembrane space (proton concentration is lower in the matrix)
Negatively
Higher
____ ____ is an inhibitor of nucleotide transport in and out of the mitochondria
Bongkrekic acid
Mitochondrial dysfunction can lead to the formation of the ____ ____ ____ ___ (MPTP), a large complex between ANT and VDAC. This pore causes _____ of mitochondrial membrane, and disrupts the proton gradient
Mitochondrial permeability transition pore
Depolarization
______ regulates the formation of MPTP. A high electrochemical gradient inhibits it’s formation. ____, _____, and ____ promote MPTP formation
Cyclophilin D
Calcium
Inorganic phosphate
ROS
Activation of MPTP can lead to ____ or ____ (non programmed cell death).
Apoptosis
Necrosis
_____ is released through the MPTP and signals for cell death. Cytochrome C forms a complex with ____ which activates a cascade of caspase proteases
Cytochrome C
Apaf-1
