Oxidative Phosphorylation II Flashcards
The catalytic domain, which binds ADP and Pi and catalyzes the reaction to form ATP
The F1 part of ATP synthase
A molecule which binds to the Fo portion of ATP synthase. It blocks the proton pathway in Fo, and prevents the reentry of protons into the matrix of the mitochondria
Oligomycin
Oligomycin prevents
ATP synthesis
During the normal tight coupling of electron transport and ATP formation, the inhibition of ATP formation will also prevent the
Oxidation-reduction reactions
What are two inhibitors of Complex I?
Amytal and Rotenone
What is an inhibitor of complex III?
Antimycin A
What are three inhibitors of complex IV?
Cyanide, CO, and sodium azide
Electrons will build up on the substrate side of the inhibited complex, making all components 100%
Reduced
All electron transport chain components on the oxygen side of the inhibitor blockage will be 100%
Oxidized
Binds to the oxidized form of the heme iron in cytochrome a3, and keeps this cytochrome permanently in its oxidized form
Cyanide (CN)
With Cyanide poisoning, complex IV can never be reduced by
Cytochrome C
Lethal because it blocks all ATP formation
Cyanide poisoning
Has a very high affinity for cyanide (again it is the oxidized heme iron)
MetHb
So if a person has gotten CN poisoning, the goal is to convert about 20-25% of their hemoglobin to
MetHb
This MetHb will bind tightly to any free CN ions in the
Blood
Starts the conversion of Hb to MetHb
Sodium nitrate
The CNMetHb can be converted to thiocyanite after the addition of
Na-thiosulfate
Usually the rate of electron transport (or respiration) is tightly coupled to our bodies
ATP needs
When ATP levels are high, the rate of electron transport
Slows down
When ATP levels are low (and ADP levels high), the rate of electron transport speeds up, to quickly make more
ATP
However, there are compounds which uncouple electron transport from ATP formation. When uncoupling occurs, the respiration rate is very fast, but
No ATP is made
When there is no ATP being formed, all of the energy from the oxidation reduction reactions of electron transport goes into
Heat
Uncouplers make the inner mitochondrial membrane “permeable” to
Protons
Usually, the rate of electron transport is limited by the creation and dissipation of the proton gradient. In the presence of an uncoupler, the oxidation-reduction reactions keep going very fast and keep pumping out protons, but a gradient is
Never formed
The net result is that respiration continues at a maximal rate, limited only by the supply of
NADH and FADH2
In the 1990’s, natural uncoupling proteins (UCP) were discovered in small mammals in a specialized tissue known as
Brown Adipose Tissue (BAT)
This tissue is brown because of the high concentration of
Mitochondria and vascularization
The biological role of BAT is
Heat production
Associated with heat production in brown adipose tissue
UCP1 (thermogenin)
The major function of brown adipose tissue is
Nonshivering thermogenesis
In response to cold, sympathetic nerve endings release norepinephrine, which activates a lipase in brown adipose tissue that releases fatty acids from
Triacylglycerols
Fatty acids serve as a fuel for the tissue and participate directly in the proton conductance channel by activating
UCP1
When UCP1 is activated by fatty acids, it transports protons from the cytosolic side of the inner mitochondrial membrane back into the mitochondrial matrix without
ATP generation
Thus, it partially uncouples oxidative phosphorylation and generates additional
Heat
Inhibitors bind to a component of the electron transport chain, stop the oxidation-reduction reactions; no electron transport; no ATP formation. These inhibitors are
CN, Antimycin A, Rotenone
Allows protons to pass freely through the inner mitochondrial membrane, so a proton gradient cannot be built up
Uncouplers
