Atractyloside Bongkrekic Acid MOA?
Inhibits ADP/ATP transport. ATR. prevents binding
of ADP. B.A. prevents release of ADP
Atractyloside Bongkrekic Acid sx?
Convulsions of a hypoglycemic nature (logical, isn't it?), collapse, death
Uncouplers uncouple ____ from phosphorylation
The effect of uncouplers on respiratory control. Uncouplers stimulate ____ in the absence of ADP.
Uncouplers dissipate the proton gradient by providing an
alternate route for proton re- entry into the matrix
what happens in absence of a graident?
the synthase runs in reverse hydrolyzing ATP.
Properties of uncouplers?
weak acids, hydrophobic, delocalized charge
A natural ____ present in mitochondria of brown adipose tissue is involved in non-shivering thermogenesis and weight regulation
structure of the uncoupler protein in the mitocondria of brown adipose tissue. what regulates it?
The uncoupler protein contains a proton pore which is under careful hormonal regulation
Oligomycin blocks ___
Oligomycin blocks ADP- but not
uncoupler- stimulated respiration.
Oligomycin blocks proton movement through ___
why does respiration slow with olgiomycin?
protons no longer reenter the matrix through FoF1.
Uncouplers stimulate respiration, but ____.
no ATP is made.
A natural phosphorylation inhibitor (the inhibitor protein) protects against
rapid ATP hydrolysis during ischemia
when does the natural phosphorylation inhibitor bind to FoF1? how?
in the absence of O2, the pH of the matrix space drops and the inhibitor protein is protonated changing its conformation to a form that binds tightly to FoF1.
Oxygen consumption measurement showing effect of cyanide
what is blocked?
ADP- and uncoupler-stimulated respiration are blocked.
In heart mitochondria, the response to cyanide is
the inhibitor protein will bind to the ATP synthase to inhibit ATP hydrolysis.
(like with ischemia)
Cyanide acts by competing with O2 for binding to(3)
the heme a3 iron and CuB.
Unlike O2, CN- cannot accept ___
The basic premise of the chemiosmotic theory is that a ____ gradient is a required intermediate in coupling the exergonic redox reactions to the endergonic synthesis of ATP
Mitchell proposed a ___ mechanism for generating the gradient called: “Mitchell’s Loops”.
the net result of a mitchells loops like Q
two protons have been transported out of the mitochondrion against an electrochemical gradient.
Mitchell’s proposed Loops cannot function in
cytochrome oxidase, since tehre is no hyodrgen donor/acceptor
The principle of pumps is that proton transport is coupled to ____ indirectly through protein conformational changes
exergonic redox reactions
The FoF1-ATP synthase is now recognized to be a tiny molecular motor. Instead of being driven by a current of electrons it is driven by
current of protons
Shuttles of reducing equivalents from glycolytic NADH to the Respiratory Chain.
(1) Glycerol phosphate shuttle
(2) Malate/aspartate shuttle
ADP/ATP and Pi Translocases
involves One ADP moves in and one ATP moves out with the net exit of
one negative charge (electrogenic).
One P - and one H+ move in with a net loss of one H+
2 predictions by mitchell
1. membranes impermeable to protons
2. electrochemical gradient exists
2 things are needed for mitchells loops to work (q cycle)
alternate between electron donors
and hydrogen donor acceptors
and you are going to alter which
side of the membrane reduction and