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APO510 - MEDICAL BIOCHEMISTRY > WEEK 2: ETS & Oxidative phosphorylation > Flashcards

WEEK 2: ETS & Oxidative phosphorylation Flashcards

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USMLE® Step 1 flashcards
1
Q

how do NADH and FADH2 give free energy to the ETS?

A

NADH and FADH2 contain energy obtained from catabolism – they get re-oxidised by transferring electrons to components of the mitochondrial Electron Transport System (ETS)

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2
Q

how is the energy produced in the ETS used?

A

ATP formation

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3
Q

what is the final electron acceptor from the ETS? What is produced?

A

O2
H2O produced

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4
Q

what is a reducing agent?

A

a substance that donates electrons

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5
Q

what is an oxidising agent?

A

a substance that receives electrons

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6
Q

what is the redox equation between redox pairs NADH and O2?

A

1/2O2 + NADH + H+ —> H2O + NAD+

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7
Q

describe REDOX POTENTIALS AND FREE ENERGY in ETS.

A
  • In the ETS, electrons are passed from one redox pair to the next –eventually to O2
  • The acceptor must have a more positive redox potential than the donor
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8
Q

where are enzymes of the ETS and ATP synthase found?

A

in the inner mitochondrial membrane

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9
Q

how is a chemical gradient established in mitochondria?

A

Inner membrane cristae (folds) increase membrane surface area and its impermeability allows the establishment of chemical gradients

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10
Q

what is the function of the ETS?

A

ETS – function is to regenerate NAD+ and FAD, with the free energy released used to generate ATP, and with the reduction of oxygen to water

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11
Q

what does FAD do?

A

transfers electrons as hydrogen atoms

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12
Q

what is the role of coenzyme Q in the ETC?

A

Acts as a link between Complex I or II and Complex III

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13
Q

describe the ETS sequence

A

NADH -> Complex I -> Complex II -> CoQ -> Complex III -> Cyt C -> Complex IV -> O2

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14
Q

how is e- transferred from complex 1 to CoQ?

A

Contains 6-7 Fe-S clusters through which e- are carried in a zig-zag pattern and transferred to CoQ

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15
Q

give the function of complex 1

A

Functions to oxidize NADH and reduce Coenzyme Q

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16
Q

give the function of complex 2

A

Functions to oxidize succinate via the generation of FADH2.
Reduces Coenzyme Q.

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17
Q

why doesn’t complex 2 pump H+ across membrane?

A

not enough energy to pump H+ across the membrane, also not a membrane spanning complex, like complex I, so cannot act as a proton pump

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18
Q

give the function of complex 3

A

Functions to oxidize Coenzyme Q and reduce Cytochrome c

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19
Q

give the function of complex 4

A

Functions to oxidize cytochrome c and reduce oxygen to water. Again is a large membrane spanning complex that contains binding sites for cytochrome c and molecular oxygen

20
Q

which complexes donate electrons to complex 5?

A

complex 1,3,4

21
Q

How much ATP is produced through oxidative phosphorylation?

A

Approximately 2.5 ATP for each NADH reoxidised and 1.5ATP for each FADH2 reoxidised

22
Q

How does the NADH produced in glycolysis get reoxidised under aerobic conditions?

A

It gets reoxidised by components of the glycerol-3-phosphate shuttle or the aspartate-malate shuttle system

23
Q

why are shuttles needed for NADH in aerobic conditions?

A

NADH produced in cytosol has to be reoxidised

24
Q

describe the cycle of the glycerol 3-phosphate shuttle.

A
  • NADH must be reoxidised to NAD+
  • dihydroxyacetone phosphate reacts with NADH to produce glycerol 3-phosphate and NAD+
  • glycerol 3-phosphate reoxidises FAD to “reproduce” dihydroxyacetone phosphate and FADH2
  • FADH2 then transfers e- to CoQ
25
Q

what is the ATP yield when a glycerol 3-phosphate shuttle operates (which is in most tissues)?

A

ATP yield = 1.5
NADH cytosol
FADH2 mitochondrion

26
Q

describe the cycle of the aspartate-malate shuttle.

A

ppppppp

27
Q

how ,many protons are pumped through complex 1, 3 and 4 per cycle?

A

complex 1 - 4
complex 3 - 4
complex 4 - 2

28
Q

what is proton motive force?

A

the force that promotes movement of protons across membranes downhill the electrochemical potential that wishes to re-establish equilibrium.

29
Q

what does the chemostatic mechanism involve?

A

the storage of energy in the form of a proton gradient, which is then used to facilitate the phosphorlyation of ADP to ATP by the ATP snythase complex.

30
Q

what is uncoupling?

A

it occurs when H+ re-enter the mitochondrial matrix without going through ATP synthase.
can be brought about by chemicals or physiologically by uncoupling proteins

31
Q

what does uncoupling result in?

A

increased O2 consumption and release of energy as heat

32
Q

IMPORTANT
name 3 chemical uncouplers.

A

2,4-Dinitrophenol
Valinomycin
Gramicidin A

33
Q

what is 2,4-DInitrophenol? How does it work?

A

A chemical uncoupler.
It crosses the inner mitochondrial membrane and releases protons in the matrix - reduces proton gradient

34
Q

how does valinomycin work?

A

a chemical uncoupler that is an antibiotic that makes the inner MM permeable to K+ and dissipates the membrane potential

35
Q

how does gramicidin A work?

A

a chemical uncoupler that is a channel forming drug - makes the inter MM permeable to protons and reduces the proton gradient

36
Q

why are physiological uncouplers most likely to be used?

A

an organ need to generate more heat for thermal regulation

37
Q

which uncoupling protein contributes to thermal regulation?

A

UCP1 - thermogenin expressed in brown adipose tissue

38
Q

what do uncoupling proteins (UPC) do?

A

form channels through the inner membrane which conduct H+ back into the matrix

39
Q

what are the 5 UPCs? Where are they expressed?

A

UCP1 - in brown adipose tissue
UCP2 - most cells
UCP3 - skeletal muscle mainly
UCP4 and 5 - brain

40
Q

how do inhibitors of the ETS work?

A

inhibitors are poisons!!
Inhibits electron flow, proton pumping and reducting of ATP synthesis.

41
Q

how does absence of O2 result in inhibition of ETS?

A

no terminal acceptor

42
Q

how does iron deficiency result in inhibition of the ETS?

A

no iron for cytochromes or Fe-S

43
Q

regarding ADP and ATP, describe the resting state.

A

ADP is low and ATP conc is high - no need for ETC so low O2 consumption

44
Q

describe the activity state regarding ATP and ADP.

A

ADP conc is high and ATP conc is low - switch on ETC and increase O2 consumption

45
Q

how does ATP, ADP and Pi transport through outer membrane?

A

via voltage dependent anion channels (VDACs)

46
Q

what is the FINAL general equation for the overall aerobic breakown of glucose?

A

glucose + 6O2 = 30ADP + 30Pi —> 6CO2 +6H2O + 30ATP

47
Q

what is the FINAL general equation for the overall anaerobic breakown of glucose?

A

glucose + 2ADP + 2Pi —> 2lactate + 2ATP

APO510 - MEDICAL BIOCHEMISTRY (12 decks)

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