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MCP > Oxidative Phosphorylation > Flashcards

Oxidative Phosphorylation Flashcards

1
Q

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

A

uncoupler

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2
Q

mechanism fo action of 2,4-dinitrophenol

A

Discharges the pH gradient

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3
Q

2,4-dinitrophenol sx? use?

A

Marked increase in metabolism profuse sweating, collapse, death.

Formerly used for weight reduction

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4
Q

what class is Gramicidin?

A

Ionophores

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5
Q

what sit he mechanism of action of Gramicidin

A

Forms a membrane pore permeable to protons

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6
Q

what are the sx of Gramicidin

A

Antimicrobial at low concentration. High concentration is fatal

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7
Q

what class is valinomycin?

A

Ionophores

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8
Q

Valinomycin mechanism of action

A

A membrane soluble, diffusional carrier of K+

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9
Q

valinomycin sx?

A

fatal

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10
Q

Oligomycin is a ___

A

Phosphoryl- ation
Inhibitors

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11
Q

Oligomycin MOA?

A

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

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12
Q

sx of Oligomycin

A

Fatal

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13
Q

what are the Inhibitors of Electron

Transport? (5)

A
  1. Rotenone
  2. Amytal (barbiturates)
  3. Antimycin A
  4. CN-
  5. CO
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14
Q

Rotenone MOA

A

inhibits chain at 1st coupling site

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15
Q

Rotenone sx? uses?

A

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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16
Q

what meds Inhibits chain at 1st coupling site?

A

Amytal (barbiturates)

rotenone

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17
Q

Amytal (barbiturates) sx?

A

Nausea, vomiting, convulsions, death from respiratory paralysis.

(same as rotenone)

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18
Q

Antimycin A MOA

A

Inhibits chain at 2nd coupling site

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19
Q

Antimycin A sx? uses?

A

Fatal, used as fungicide and insecticide

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20
Q

CN- mOA

A

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

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21
Q

CN- sx?

A

Convulsions, unconsciousness, death from respiratory paralysis.

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22
Q

cyanide antidote

A

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

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23
Q

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

A

CN and CO

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24
Q

what does death from co result from?

A

interaction with hemoglobin before it can reach the respiratory chain.

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25
Q

sx of CO poisoning

A

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

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26
Q

what to tx CO poisoning with

A

O2

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27
Q

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

A

Atractyloside Bongkrekic Acid

Mercurous salts

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28
Q

Mercurous salts sx

A

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

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29
Q

Mercurous salts MOA

A

Inhibits Pi transport by
reaction with essential - SH

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30
Q

what were Mercurous salts formely used for?

A

treating syphilis

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31
Q

Atractyloside Bongkrekic Acid MOA?

A

Inhibits ADP/ATP transport. ATR. prevents binding
of ADP. B.A. prevents release of ADP

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32
Q

Atractyloside Bongkrekic Acid sx?

A

Convulsions of a hypoglycemic nature (logical, isn’t it?), collapse, death

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33
Q

Uncouplers uncouple ____ from phosphorylation

A

oxidation

34
Q

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

A

oxygen consumption

35
Q

Uncouplers dissipate the proton gradient by providing an

A

alternate route for proton re- entry into the matrix

36
Q

what happens in absence of a graident?

A

the synthase runs in reverse hydrolyzing ATP.

37
Q

Properties of uncouplers?

A

weak acids, hydrophobic, delocalized charge

38
Q

A natural ____ present in mitochondria of brown adipose tissue is involved in non-shivering thermogenesis and weight regulation

A

uncoupler

39
Q

structure of the uncoupler protein in the mitocondria of brown adipose tissue. what regulates it?

A

The uncoupler protein contains a proton pore which is under careful hormonal regulation

40
Q

Oligomycin blocks ___

A

ADP

41
Q

Oligomycin blocks ADP- but not

A

uncoupler- stimulated respiration.

42
Q

Oligomycin blocks proton movement through ___

A

FoF1

43
Q

why does respiration slow with olgiomycin?

A

protons no longer reenter the matrix through FoF1.

44
Q

Uncouplers stimulate respiration, but ____.

A

no ATP is made.

45
Q

A natural phosphorylation inhibitor (the inhibitor protein) protects against

A

rapid ATP hydrolysis during ischemia

46
Q

when does the natural phosphorylation inhibitor bind to FoF1? how?

A

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.

47
Q

Oxygen consumption measurement showing effect of cyanide

what is blocked?

A

ADP- and uncoupler-stimulated respiration are blocked.

48
Q

In heart mitochondria, the response to cyanide is

A

the inhibitor protein will bind to the ATP synthase to inhibit ATP hydrolysis.

(like with ischemia)

49
Q

Cyanide acts by competing with O2 for binding to(3)

A

the heme a3 iron and CuB.

50
Q

Unlike O2, CN- cannot accept ___

A

electrons

51
Q

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

A

delocalized electrochemical

52
Q

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

A

direct coupling

53
Q

the net result of a mitchells loops like Q

A

two protons have been transported out of the mitochondrion against an electrochemical gradient.

54
Q

Mitchell’s proposed Loops cannot function in

A

cytochrome oxidase, since tehre is no hyodrgen donor/acceptor

55
Q

The principle of pumps is that proton transport is coupled to ____ indirectly through protein conformational changes

A

exergonic redox reactions

56
Q

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

A

current of protons

57
Q

Shuttles of reducing equivalents from glycolytic NADH to the Respiratory Chain.

A

(1) Glycerol phosphate shuttle
(2) Malate/aspartate shuttle

58
Q

ADP/ATP and Pi Translocases

involves One ADP moves in and one ATP moves out with the net exit of

A

one negative charge (electrogenic).

One P - and one H+ move in with a net loss of one H+

59
Q

2 predictions by mitchell

A

predictions

  1. membranes impermeable to protons
  2. electrochemical gradient exists
60
Q

2 things are needed for mitchells loops to work (q cycle)

A

alternate between electron donors
and hydrogen donor acceptors

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

61
Q

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

A

against the gradient

driven by redux reactions

62
Q

stoichimotery of mithcells loops?

A

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

63
Q

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

A

Q

64
Q

Q must also pick up ___ from the aqueous inside phase

after getiting electron from iron-sulfur center of a dehydrogenase and Cyt bh

A

2 H+

65
Q

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

A

diffuse outside surface to be oxidize

66
Q

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

A

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

67
Q

once Q gets rid of its electrons..

A

loses both hydrogens to become fully oxidized

then diffuses back inside to begin next cycle

68
Q

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

A

electrons but not the required protons

protons are received from the matrix

69
Q

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

A

oxidized

70
Q

where does Q dump the protons?

A

in the intermembrane space

71
Q

explain the rotatry wheel of atp synthease

A

A H+ enters a channel and hops on to c subunit

c subunit rorates until the proton is aligned with a second channel

  1. c rotary wheel is anchored to γ, when c subunits rotate realtive to a, γ is forced to rotate relative to the catlaytic subunits
  2. the drive is protons moving down gradient is coupled with need to break atp off, allowing atp to be broken off
72
Q

The ___synthase is now recognized to be a tiny molecular motor.

A

FoF1-ATP

73
Q

what are the only known proton driven rotary motor

A
  • bacterial flagella motor
  • FoF1-ATP synthase
74
Q

with Glycerol phosphate shuttle you only get ___ atp

A

2 atp/2 e

75
Q

why do you only get 2 atp with Glycerol phosphate shuttle

A

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

76
Q

Malate/aspartate shuttle gives ____ atp

A

3 atp/2e

77
Q

Malate/aspartate shuttle (~3 ATP/2 e-) present in___

A

liver and heart

78
Q

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

A

some muscle and nerve cells.

79
Q

adp/atp trnsslocator is ___

A

electrogenic

bc you are eliminating one of the positive charges

80
Q

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

A

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

81
Q

what are the roles of H gradient?

A

MCP (16 decks)

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