Mitochondrial Respiratory chain and Oxidative Phosphorylation Flashcards

1
Q

What is the inner membrane of the mitochondria impermeable to?

A
  • small molecules and ions
  • including H+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Overview of the electron transport chain

A
  • complex 1, complex 2, Q , complex III,
    complex C (cytochrome C), complex 4
  • enter electrons as NADH into complex 1
    OR as FADH2 into complex 2
  • electrons are shuttled by Q into complex 3
  • movement of electrons shifts protons
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Complex 1 of the mitochondrial respiratory chain:

A
  • 2 electrons from NADH pass to FMN
  • electrons pass one at a time through a
    series of Fe-S centers to UBIQUINONE
    (coenzyme Q) to form QH2 = exergonic
  • Fe is positive and attracted to negatively
    charged electrons; motion of electrons
    causes a conformational change to
    complex 1 and releases energy
  • QH2 diffuses into the lipid bilayer
  • Flow of electrons transduced into H+
    PUMPING = endergonic

***overall reaction: NADH + H+ + Q -> NAD+
+ QH2

complex 1 = proton pump

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Complex 1 of the mitochondrial respiratory chain

A
  • large portion of complex 1 is embedded in
    the mitochondrion matrix
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Complex 2 of the mitochondrial respiratory chain:

A
  • enzyme succinate dehydrogenase
  • also part of the TCA cycle converting
    succinate to fumurate
  • TCA: succinate binds to subunit A and
    passes electrons to FAD. FAD reduced to
    FADH2 at binding site
  • FADH2 moves through FE-S centers (Fe
    positive etc)
  • transferred to ubiquinone to form reduced
    ubiquinol QH2
  • Heme b not part of pathway: prevents
    stray electrons forming damaging ROS
    (reactive oxygen species)
  • complex 2 = NOT a proton pump
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Complex 2 of the mitochondrial respiratory chain:

A
  • also large portion is present in the
    mitochondrial matrix
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Ubiquinone (5):

A
  • lipid soluble
  • can accept one e- or 2 e- to become
    ubiquinol QH2
  • freely diffusible within lipid bilayer of inner
    mitochondrial membrane
  • shuttles electrons between other less
    mobile electron carriers
  • central role in coupling electron flow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Ubiquinol serves as an —— —– for electrons into the electron transport chain from pathways other than ——- or —.

A
  • entry point
  • complex 1
  • complex 2
  • can be from G3p or fatty acid metabolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Complex III of the mitochondrial respiratory chain:

A
  • couples the transfer of 2 e- from ubiquinol
    (QH2) to 2 molecules of CYTOCHROME C
  • in the process, 4 MORE PROTONS (H+) are
    transported from the matrix into the
    intermembrane space
  • complex is made of two identical porteins
    with 11 subunits
  • ubiquinone can shuttle between two
    binding sites; Qn (matrix side) and Qp
    (intermembrane side) transferring protons
    and electrons

complex III = proton pump

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Cytochrome C of the mitochondrial respiratory chain:

A
  • soluble protein of the intermembrane
    space (electron carrier)
  • can accept one electron (Fe2+ -><- Fe3+)
  • once its haeme group has accepted an
    electron from complex III it moves to
    donate its electron to complex IV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Complex IV of the mitochondrial respiratory chain:

A
  • cytochrome oxidase
  • two cytochrome C each donate one
    electron to a copper center
  • OXYGEN now binds to haema and accepts
    donate electrons
  • delivery of two more electrons creates
    O22- which combines with 4 H+ from the
    matrix to produce water
  • in the process, 4H+ are pumped across the
    from the matrix into the inter membranal
    space

complex IV = proton pump

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

For every 1 NADH molecule how many protons are pumped during the mitochondrial respiratory chain?

A

10 protons pumped across the inner mitochondrial membrane

complex 1 = 4
complex 3 = 4
complex 4 = 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Reduction potentials drive the transfer of electrons along the electron transport chain:

A
  • redox potential becomes more positive
  • downhill attraction (exergonic)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Synthesis of ATP:

Inner mitochondrial membrane is generally impermeable to ions, but 3 specifc systems in the membrane:

A

1) Transport ADP and Pi into the matrix
(substrates for substrate level
phosphorlyation
2) synthesise ATP
3) transport ATP into the cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Chemiosmotic model of ATP synthesis:

A
  • utilises electrical and chemical potential
    energy: PROTON MOTIVE FORCE
  • caused by difference in H+ conc acrosss
    inner membrane provided by proton
    pumping of the ETC
  • proton motive forces drive synthesis of
    ATP using ATP synthase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

ATPase Structure: F0:

A
  • functional domain
  • oligomycin sensitive proton channel
17
Q

ATPase Structure: F1:

A
  • functional domain
  • projects into the matrix of the mitochondria
18
Q

F1 domain of ATPase: subunits:

A
  • nine subunits: alpha x3, beta x3, gamma,
    delta, epsilon
  • Beta and alpha are arranged alternatively
  • gamma = rod in middle
  • delta on the side
19
Q

Beta (x3) subunits of F1 domain of ATPase:

A

have catalytic sites for ATP synthesis

20
Q

Binding-Change model for ATP syntehsis:

A
  • 3 beta subunits take it in turns to catalyse
    ATP synthesis
  • any given beta subunit starts in a
    conformation for binding ADP and Pi (B-
    ADP conformation)
  • the beta subunit changes conformation so
    the active site now binds the ATP product
    tightly (B-ATP conformation)
  • the beta subunit changes conformation
    again to give the active site a very low
    affinity for ATP (B-empty conformation) so
    ATP is released
21
Q

Rotational Catalysis: Binding-Change model for ATP synthesis:

A
  • the PROTON MOTIVE FORCE causes
    rotation of the shaft (gamma subunit)
  • the shaft rotates 120 degrees and touches
    each ab subunit in turn
  • *** causes a change in the conformation
    of beta subunit, altering its ADP/ATP
    binding properties
  • the F1 subunits interact with each other: if
    one subunit takes on the B-empty
    conformation, its neighbour must adop B-
    ADP and the other B-ATP
22
Q

During the mitochondrial respiratory chain how much ATP is made?

A
  • each NADH will pump 10H+ into the
    mitochondrial intermembrane space
  • each succinate via FADH2 will pump 6H+
    into the intermembrane space
    • 4 are used to fully make 1 ATP!!!!
  • 3H+ used in ATP synthesis
  • 1H+ used in Pi, ATP, ADP transport
23
Q

ATP yield from complete oxidation of 1 glucose molecule:

A

total 30 or 32

24
Q

Malate-Aspartate Shuttle

A

Oxaloacetate turned into malate using malate dehydorgenase and producing NAD+

Malate alpha ketoglutarate transporter takes malate from intermembrane space into the matrix

Malate dehydrogenase then converted by malate dehydrogenase into oxaloacetate and produces NADH

Aspartate aminotransferase changes oxoaoacetate in the matrix into aspartate which travels through the glutamate-aspartate transporter

aspartate in the intermembrane space and is converted to oxaloacetate using aspartate aminotransferase

***purpose = moving NADH produced during glycolysis into the matrix for use by complexes during oxidative phosphorylation

insert slide

25
Q

Glycerol-3-Phosphate shuttle:

A
  • MAKES LESS ATP BECAUSE LESS PROTONS
    PUMPED AS COMPLEX 2 IS NOT A PROTON
    PUMP
26
Q

Uncoupling Reagants

A
  • normally e- flow and phosphorylation are
    tightly coupled
  • uncouplers dissipate the pH gradient by
    transporting H+ back into the matrix so
    **bypassing ATP synthase
  • thus an uncoupler (eg DNP) severs the link
    between e- flow and ATP synthesis, with
    energy released as heat
27
Q

Uncoupling and Brown Fat: thermogenesis:

A
  • brown adipose fat: specialised for heat
    generation
  • high numbers of mitochondria can cause
    brown appearance
  • mitochondria contain thermogenin UCP1
    receptor provides an alternative route for
    protons to re-enter the matrix cauisng
    energy conserved by proton pumping to be
    dissipated as heat
  • ***important in new borns
28
Q

Brown adipose tissue location

A
  • between shoulder blades
  • surrounding kidneys
  • neck
  • along the spinal cord
29
Q

Exogenous uncoupling agent: 2,40dinitrophenol:

A
  • soluble weak acid
  • carries H+ across membrane
  • dissipating the proton gradient
  • uncouples electron transport from
    oxidative phosphorylation which raises the
    metabolic rate
  • toxicity arises from liver damage,
    respiratory acidosis and hyperthermia
30
Q

How can NADH from glycolysis be transported into the mitochondrial matrix for use during oxidative phosphorylation?

A

1) Malate-Aspartate
2) Glyceraldehyde 3-phosphate shuttle