SYLLABUS 11-12: Bioenergetics Flashcards Preview

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Flashcards in SYLLABUS 11-12: Bioenergetics Deck (59):
1

what does oxidative phosphorylation do

converts energy derived from oxidation of glucose, fatty acids, and amino acids to ATP's high-energy phosphate bonds

2

where does oxidative metabolism take place

mitochondria 

 

3

function and location of the electron transport chain?

oxidizes energy, from oxidation of fuels in TCA cycle and B-oxidation of fatty acids, conserved in NADH and FADH2, 

via a series of enzymes embedded in mito inner membrane

 

4

what is final acceptor of H's from NADH and FADH2 in the etc?

oxygen

makes H2O 

5

how does structure of the mito impact ETC?

outer membrane is permeable to everything 

folded inner membrane contains respiratory/ETC and its enzymes - which are linked to enzymes that make ATP, the ATP synthesis enzymes

6

how are electrons transferred, broadly, in mito resp chain?

e- are transferred from NADH/FADH2 via ubiquinone, coenzyme Q, and cytochromes to molecular O2

molecular O2 is reduced to H2O 

energy from oxidation of NADh and FADH2 by O2 is used to produce ATP from ADP + Pi by ATP synthase, FoF1 ATPase complex

7

what is chemiosmotic model

explains how energy from transport of electrons to O2 is transformed into the high energy bonds of ATP 

 

8

what kind of rxns cause transfer of e- in the etc?

oxidation-reduction steps as electrons pass through complexes of proteins that span the mito inner membrane

9

what generates electrochemical gradient across mito inner membrane?

as e- pass through complexes in inner mito membrane, pumping of protons from mito matrix to cytosolic side of inner mito membrane 

10

what comprises delta-P?

electrochemical gradient across mito inner membrane 

= a membrane potential beacuse of pumping positive charges out of the mito 

AND a proton gradient b/c of pumping protons out of the mito 

11

what is the ratio of H+ pumped/e- passing through for each of the complexes of the etc?

Complex I: 4H+ pumped per electron

Complex III: 2H+ per electron 

Complex IV: 4H+ per electron 

 

this generates electrochemical gradient across membrane

12

structure of the ATP synthase?

a proton pore through the inner membrane and a catalytic head-piece that protrudes into the matrix 

 

13

how does ATP synthase function?

protons that were pumped out during e- transport to O2 re-enter via the proton pore of the ATP synthase complex 

this causes conformation change in catalytic headpiece

this change releases ATP bound to 1 site, and catalyzes formation of a new ATP from ADP + Pi at another site 

the newly formed ATP is transferred to the bound site, will be released by next proton entering the proton pore

14

how can we categorize the process that the ATP synthase complex facilitates?

oxidative phosphorylation - transfer of e- and pumping of protons is coupled to synthesis of ATP 

15

what defines the rate of respiration in the etc?

1) transfer of electrons 

2) reduction of O2

16

what regulates the rate of respiration in the etc?

1) rate of ATP synthesis 

2) delta-P 

3) other bioenergetic work functions which utilize the delta-P

17

what is difference in effect on etc action between if delta-P is utilized/not utilized?

if delta-P is not utilized, rate of e- transfer or O2 uptake decreases b/c of back pressure exerted on respiratory chain by high accumulated delta-p 

 

if delta-p is utilized for ATP synthesis or bioenergetic work functions, the rate of e- transfer becomes faster in order to keep generating the delta-P

18

how does the permeability of the mito inner membrane impact the respiration rate?

membrane's impermeability to protons means that protons are pumped out only at discrete sites in complexes I, III, IV, and pumped back in through proton pore of ATP syntase (links oxidation-phosphorylation) 

 

 

19

what can make mito inner membrane permeable? 

what's the impact?

damage or chemical modification by uncoupling agents to mito inner membrane makes it leaky to protons 

a delta-P will be immediately dissipated, since pumped-out protons non-specifically re-enter the mito rather than re-enter through proton pore of ATP synthase

20

what are uncoupling agents 

proteins that form channels through the mito inner membrane for protons to pass from the intermembrane (cytosolic) space to the matrix 

thus short-circuits the ATP synthase 

 

21

what happens to the delta-P and respiratory chain in the presence of an uncoupling agent?

lose delta-p beacuse discharge the gradient by carrying protons back into the mitochondria 

respiratory chain still is working, so get movement of e- through the chain, but do not make any ATP 

this uncouples phosphorylation and oxidation 

22

UCP1 action?

associated w/ heat production in brown adipose tissue 

important for infants to maintain body temp and for animals to hibernate 

23

UCP3 action?

in skeletal muscle 

drug target for obesity - idea that if find activators of UCP3 to "waste" the delta-P as heat rather than use it to support fat synthesis reactions

24

what is only part of the etc that isn't protein-bound?

ubiquinone

25

how is ubiquinone synthesized?

from an intermediate produced during cholesterol synthesis 

26

what is complex I? what does it contain? what does it do?

Complex I: NADH Dehydrogenase or NADH:Coenzyme Q oxidoreductase complex 

contains: iron-sulfur (FeS) proteins, FMN (flavin mononucleotide) 

e- pass from NADH -> FMN -> FeS centers -> ubiquinone (Q) 

this reduces QH2, reduced ubiquinone 

 

 

27

Complex II name? 

What does it contain? 

What does it do?

Complex II = Sucicnate Dehydrogenase (TCA cycle enzyme) 

Contains: FAD 

e- from succinate pass to FAD to Q, produces QH2 

 

28

what processes do e- from FADH2 come from?

how do they enter the etc?

FADH2 are produced by B-oxidation of fatty acids and by a-GP shuttle 

e- from FADH2 pass on to Q via electron transfer flavoprotein

produces QH2

29

are protons pumped out of mito by complex II?

no

30

how many e- do NADH and FADH2 transfer to Q?

rate? result of this?

2 e- 

Q can accept e- 1 at a time 

this produces the ubisemiquinone radical before the HQ radical accepts the 2nd electron to produce QH2, reduced ubiquinone 

 

31

what are the cytochromes?

proteins containing hemes in which the iron in the heme unergoes oxidation-reduction

32

what is the name of Complex III? 

what does it contain?

what is its action? 

Complex III: B:c1 complex 

Contains: cytochromes b and c1 and iron-sulfur centers 

QH2 passes 1 e- at a time to Cyt b (Fe 3+) to produce reduced Cyt b (Fe2+) which reduces the FeS, which reduces Cyt C1, which reduces Cyt c (Fe3+) to reduced Cyt C (Fe2+ 

b:c1 complex pumps 2 protons out/electron

33

what is complex IV? 

what does it contain? 

what is its action?

Complex IV: Cytochrome Oxidase complex 

Contains: Cytochromes a and a3 and 2 major copper centers, CuA and CuB 

Reduced Cyt C passes 1 e- at a time through Complex IV: reduces CuA, then Cyt A, then CuB, then Cyt a3 

34

how many e- are needed to reduce molecular O2 to H2O?

when does this occur?

4 e-: 

O2 + 4H+ + 4e- -> H2O 

this occurs via complex IV, means that complex IV has 4 H+ pumped out/e- passing through

35

how does the ATP synthase complex work?

protons enter the proton pore in the top from the cytosolic side of the mito inner membrane 

conformational changes occur in several subunits, causing rotations in the F1 rotor component

rotations discharge bound ATP and catalyze phosphorylation of ADP 

this produces a new ATP by the alpha subunit 

36

how much energy does oxidation of 1 mole of NADH and FADH2 produce?

 

NADH: 53 kCal/mol = 7-8 ATPs theoretically, 2.5 ATP actually

FADH2: 41 kCal/mol = 6 ATPs theoretically, 1.5 ATP actually 

 

thus about 25-30% of available energy from oxidation of NADh and FADH2 is trapped as ATP

37

is the respiratory chain reversible? why/why not?

no

cannot synthesize O2 from H2O

because delta-G is strongly negative 

38

what can delta-P power be used for besides ATP synthesis?

1. energized calcium uptake into the mito 

2. adenine nucleotide translocase, exchanges ADP for ATP

3. reversed electron transport 

4. transhydrogenase activity 

energy-dependent reactions, which mito can carry out using proton motor force!

39

what is transhydrogenase activity 

energy-dependent reduction of NADP+ to NAD+ and NADPH 

in presence of a delta-P, equilibrium of this changes from 1, favors reduction of NADP+ by NADH, results in NADPH utilization for biosynthetic rxns

40

why's it important that delta-P can be used for Ca2+ uptake into the mito?

Ca2+ is toxic, so Ca2+ is removed from teh cytosol, stored in the ER and the mito 

this requires a delta-P to pump Ca2+ into the mito 

41

what is reversed e- transfer?

FADH2 reducing NAD+ to produce NADH rather than NADH reducing FAD/FMN 

 

42

what is the effect of bioenergetic reactions that use delta-P, but are not the respiratory chain?

1. they compete w/ ATP for the delta-P

2. they speed up the rate of e- transfer by utilizing the delta-P 

43

what inhibits complex I?

effect?

many chemicals; often rotenone is used

in rotenone presence, reduced FMN and iron sulfur centers of Complex I accumulate

e- thus are not passed to Q, and to O2 

delta-P is not maintained -> ATP is not synthesized 

44

what inhibits complex III? 

effect?

antimycin A

QH2 accumulates, and Cyt C isn't reduced

45

what inhibits complex IV?

effect?

cyanide (CN) and carbon monoxide (CO) 

CN: reduced Cyt C accumulates 

46

what inhibits the ATP synthase complex? 

how?

oligomycin and DCCD bind to complex, block the proton pore 

thus external protons can't enter the ATP synthase complex ->

ATP isn't synthesized ->

continuous proton pumping stops b/c of back pressure of accumulated cytosolic protons ->

O2 uptake slows down 

47

what is respiratory control? 

what controls its rate? 

when is it slower, faster?

control of oxygen uptake by the delta-P aka rate of O2 uptake in presence of a respiratory chain substrate plus ADP + Pi relative to rate in presence of substrate only 

O2 uptake in substrate only is low since delta-P generated isn't being used 

O2 uptake in presence of substrate plus ADP + Pi is rapid b/c delta-P is being used to produce ATP 

48

what is the cause of mitochondrial diseases re: resp chain?

cytochrome b, 3 of 6 protein subunits of cyt. oxidase, 7 of subunits of Cojplex I, and 2 subunits of the FoF1 complex come from mito proteins encoded by mito DNA

many mitochondrial diseases rsult from mutations either in the nuclear DNA or mito DNA encoding mito proteins 

 

49

why is mito DNA prone to damage?

not protected by histones, as nuclear DNA is 

are the major generator of reactive oxygen species 

deficiencies in synthesis of parts of complexes assoc w/ mito DNA can be toxic

50

how is mito DNA inherited and trasmitted?

mito DNA is maternally inherited 

transmitted by mother to children

51

examples of mito DNA lesions in disease?

parkinson's disease, cardiomyopathies, diabetes, several neurological disorders

52

53

what is respiratory control? 

what determines it? 

Respiratory control is control of the rate of O2 uptake in the respiratory chain by the proton motor force, and it is determined by the presence of substrate plus ADP + Pi relative to the rate of substrate only

 

O2 uptake is increased when you have ADP + Pi to turn into ATP, so that cells utilize O2 only if they would take it up anyways

54

What is effect on rate of oxygen uptake and rate of ATP synthesis in presence of Substrate, ADP, plus

1) Cyanide

2) an uncoupler 

3) oligomycin 

4) uncoupler + oligomycin 

5) uncoupler + cyanide 

  1. Cyanide: no oxygen consumption because complex IV is blocked
  2. An uncoupler: rapid oxygen consumption because proton motor force is discharged
  3. Oligomycin: blocks proton core of complex V, ATP synthase, no ATP made but proton motor force functions
  4. Uncoupler + oligomycin:  same rate of O2 movement as in only uncoupler conditions; get no ATP production
  5. Uncoupler + Cyanide: rate of O2 movement goes to 0 because cyanide poisons Complex IV 

55

If Mito, substrate, ADP, Pi, and oxygen are available, 

1) what would generate a high proton motive force? 

2) what could be added to produce ATP?

  1. High proton motive force would be generated if add in malate + NADH
  2. Could add Ca2+ to produce ATP 

56

why does rotenone inhibit the MA shuttle but not the a-GP shuttle?

Rotenone inhibits the MA shuttle but not the a-GP shuttle because the malate-aspartate shuttle uses NAD+, and rotenone inhibits complex I which oxidizes NADH to NAD+, whereas complex II uses FAD from succinate, and rotenone does not inhibit complex II, and the a-GP shuttle uses FAD+ to accept e- for transfer to Q

aka FADH2 enters beyond complex I 

57

what woudl accumulate in the ETC in the presence of 

1) antimycin A 

2) cyanide

  1. QH2 would accumulate in the presence of antimycin A since antimycin A inhibits Complex III
  2. Cytochrome C1 would accumulate in the presence of cyanide since CN inhibits Cytochrome C 

58

what are mitochondrial work functions outside of the ETC that use the proton motive force?

energized Ca2+ uptake from the cyto to the matrix, transhydrogenase activity, adenine nucleotide translocase, reversed e- transport are mitochondrial work functions that can utilize the proton motive force

59

where do NADH and FADH2 used to set up the proton motive force come from?

NADH from TCA or glycolysis 

FADH2 from TCA cycle

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