Oxidative Phosphorylation Flashcards by brittany gouse

2,4-dinitrophenol is what class that prevents oxidative phosphorla?

uncoupler

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mechanism fo action of 2,4-dinitrophenol

Discharges the pH gradient

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2,4-dinitrophenol sx? use?

Marked increase in metabolism profuse sweating, collapse, death.

Formerly used for weight reduction

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what class is Gramicidin?

Ionophores

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what sit he mechanism of action of Gramicidin

Forms a membrane pore permeable to protons

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what are the sx of Gramicidin

Antimicrobial at low concentration. High concentration is fatal

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what class is valinomycin?

Ionophores

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Valinomycin mechanism of action

A membrane soluble, diffusional carrier of K+

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valinomycin sx?

fatal

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Oligomycin is a ___

Phosphoryl- ation
Inhibitors

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Oligomycin MOA?

Prevents use of the electrochem. grad. to drive ATP synthesis

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sx of Oligomycin

Fatal

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what are the Inhibitors of Electron

Transport? (5)

Rotenone
Amytal (barbiturates)
Antimycin A
CN-
CO

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Rotenone MOA

inhibits chain at 1st coupling site

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Rotenone sx? uses?

sx – Nausea, vomiting, convulsions, death from respiratory paralysis.

use – Used in a topical ointment for treatment of chiggers. Also used as a poison for harvesting fish and as an insecticide

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what meds Inhibits chain at 1st coupling site?

Amytal (barbiturates)

rotenone

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Amytal (barbiturates) sx?

Nausea, vomiting, convulsions, death from respiratory paralysis.

(same as rotenone)

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Antimycin A MOA

Inhibits chain at 2nd coupling site

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Antimycin A sx? uses?

Fatal, used as fungicide and insecticide

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CN- mOA

Inhibits chain at cytochrome a3, blocks
O2 binding by binding to FeIII

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CN- sx?

Convulsions, unconsciousness, death from respiratory paralysis.

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cyanide antidote

Antidote: nitrite and thiosulfate intravenously (oxidizes some hemoglobin to met
hemoglobin which binds CN-). Administer O2

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what Inhibits chain at cytochrome a3, blocks O2 binding by binding to FeII??

CN and CO

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what does death from co result from?

interaction with hemoglobin before it can reach the respiratory chain.

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sx of CO poisoning

Dizziness, vomiting, increase then decrease of pulse and respiration, collapse, death.

what to tx CO poisoning with

Inhibitors of mitochon- drial trans- port systems include (2)

Atractyloside Bongkrekic Acid Mercurous salts

Mercurous salts sx

Muscle spasms, depression, death from kidney failure usually within a week of exposure.

Mercurous salts MOA

Inhibits Pi transport by reaction with essential - SH

what were Mercurous salts formely used for?

treating syphilis

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

oxidation

The effect of uncouplers on respiratory control. Uncouplers stimulate ____ in the absence of ADP.

oxygen consumption

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**

uncoupler

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 \_\_\_

ADP

Oligomycin blocks ADP- but not

uncoupler- stimulated respiration.

Oligomycin blocks proton movement through \_\_\_

FoF1

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 \_\_\_

electrons

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

delocalized electrochemical

Mitchell proposed a ___ mechanism for generating the gradient called: “Mitchell’s Loops”.

direct coupling

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

predictions 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 ## Footnote and you are going to alter which side of the membrane reduction and oxidation occur

in mitchells loops, 2 protons are moving \_\_\_. this is driven by \_\_\_.

against the gradient driven by redux reactions

stoichimotery of mithcells loops?

2H+/e- or 4H+/2 e-.

On the inside surface, an iron-sulfur center of a dehydrogenase and Cyt bh donate 1 e- each to\_\_\_

Q must also pick up ___ from the aqueous inside phase after getiting electron from iron-sulfur center of a dehydrogenase and Cyt bh

2 H+

after Q picks up 2 electrons and 2 ptorons it then must ___ to be oxidized

diffuse outside surface to be oxidize

after QH2 2 electorn complex diffuses to outside surface what happens?

1 electron is rtansferred to iron sulfur center and another to cyt b

once Q gets rid of its electrons..

loses both hydrogens to become fully oxidized then diffuses back inside to begin next cycle

a hydrogen acceptor (i.e., H+ + e-) such as Q is reduced on the inside surface of the inner mitochondrial membrane by electron donors that can supply

electrons but not the required protons protons are received from the matrix

once Q is reduced, the hydrogen donor can move to be

oxidized

where does Q dump the protons?

in the intermembrane space

explain the rotatry wheel of atp synthease

A H+ enters a channel and hops on to c subunit c subunit rorates until the proton is aligned with a second channel 3. c rotary wheel is anchored to γ, when c subunits rotate realtive to a, γ is forced to rotate relative to the catlaytic subunits 4. the drive is protons moving down gradient is coupled with need to break atp off, allowing atp to be broken off

The \_\_\_synthase is now recognized to be a tiny molecular motor.

FoF1-ATP

what are the only known proton driven rotary motor

- bacterial flagella motor - FoF1-ATP synthase

with Glycerol phosphate shuttle you only get ___ atp

2 atp/2 e

why do you only get 2 atp with Glycerol phosphate shuttle

Doesn’t involve membrane transport since the mitochondrial glycerol-phosphate dehydrogenase is on the outside surface of the inner membrane. just goes to complexes 2 and 3

Malate/aspartate shuttle gives ____ atp

3 atp/2e

Malate/aspartate shuttle (~3 ATP/2 e-) present in\_\_\_

liver and heart

Glycerol phosphate shuttle (~2 ATP/2 e-), present in

some muscle and nerve cells.

adp/atp trnsslocator is \_\_\_

electrogenic bc you are eliminating one of the positive charges

One P - and one H+ move in trnaslocator results in

a net loss of one H+ from the concentration gradient i but with no change in charge (electroneutral).

what are the roles of H gradient?