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104-theme 2-the liver and regulation of metabolism > mitochondrial respiratory chain > Flashcards

mitochondrial respiratory chain Flashcards

1
Q

what is important about the inner mitochondrial membrane?

A
  • the location of the electron transfer chain
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2
Q

what is electron transport chain? 3

A
  • Comprises four large multi-unit proteins intrinsic to the inner mitochondrial membrane
  • Catalyse a series of reactions= NADH + H+ + 1/2 O2= NAD+ +H2O
  • Energy released from this reaction not released as heat, but tightly coupled to the production of ATP
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3
Q

what are the components of the electron transport chain? 5

A
  • Complex I, II, III, IV
  • These are linked by 2 soluble proteins:
  • Ubiquinone (coenzyme Q)- a lipid soluble benzoquinone with a long isoprenoid tail
  • Cytochrome c
  • These are free to move in the membrane by diffusion (they are not part of the complexes)
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4
Q

what are the protein components of the electrical chain complex? 6

A
  • I= NADH dehydrogenase
  • II- succinate dehydrogenase
  • III= ubiquinone: cytochrome c oxidoreductase
  • IV= cytochrome oxidase
  • Cytochrome c is not part of an enzyme complex, it moves between complexes III and IV as a soluble protein
  • These are really big proteins
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5
Q

describe the function of complex I? 5

A
  • Initially electrons are passed to FMN to produced FMNH2
  • Subsequently transfer to a series of iron sulphur cluster
  • Then transfer to Coenzyme Q (ubiquinone)
  • So, the enzyme catalyses the reaction: NADH + H+ + Q= NAD+ + QH2
  • It is proton pump, moving protons from the matrix to the intramitochondrial space (4H+)
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6
Q

describe the function of complex II? 3

A
  • FAD within complex II is reduced to FADH2 by electrons gained from the conversion of succinate to fumarate in the TCA cycle
  • Complex II passes’ electrons to ubiquinone
  • Other substrates for mitochondrial dehydrogenases also pass on their electrons to ubiquinone but not through complex II
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7
Q

what are the sources of electrons entering the ETC? 4

thing of note?

A
  • complex I
  • complex II
  • G-3-p shuttle
  • ETF:Q oxidoreductase which accepts electrons from FADH2 which is generated from the first step of beta oxidation of fatty acids

The route of complex II and directly to ubiquinone can bypass the release of H+ into the intramembrane space which has consequences

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8
Q

what is complex III?

A
  • Second of three proton pumps in the respiratory chain
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9
Q

what is complex IV? 3

A
  • Third and final proton pump
  • Carries electrons from cytochrome c to molecular oxygen
  • Produced water for 1/2 O2 and 2H+
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10
Q

what does cytochrome c do?

A

passes electrons from complex III to complex IV

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11
Q

what is the operation of ETC dependent on?

A
  • oxygen

- final electron acceptor

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12
Q

describe the synthesis of ATP? 5

A

ADP3- +Pi2- +H+ –> ATP4- + H2O

  • Inner mitochondrial leaflet is generally impermeable to charged species BUT 3 specific systems in this membrane that:
  • Transport ADP and Pi into the matrix
  • Synthesise ATP
  • Transport ATP into the cytosol
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13
Q

describe adenine nucleotide translocase? 6

A
  • Integral protein of the inner mitochondrial membrane
  • Transports ADP3- from the intramitochondrial membrane space into the matrix
  • In exchange for an ATP4- molecule transported in the other direction (favoured by the electrochemical gradient generated by a proton pump)
  • Known as an antiporter
  • Atractyloside, a glycoside isolated from a thistle, is a specific inhibitor of adenine nucleotide translocase= highly poisonous
  • Favoured by transmembrane gradient
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14
Q

describe phosphate translocase? 3

A
  • A second membrane transported is essential for oxidative phosphorylation and synthesis of ATP
  • Transports both phosphate and hydrogen ions in the matric: a symporter
  • Favoured by transmembrane proton gradient
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15
Q

what is ATP synthase? 4

A
  • An F-type ATPase
  • Two functional domains:
  • Fo, an oligomycin sensitive proton channel
  • Fi, an ATP synthase
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16
Q

what is the structure of ATP synthase? 9

A
  • Fo comprises three different types of subunits: a, b, c
  • Form a complex of 13-15 subunits
  • Subunits c1-10 arranged in a circle
  • F1 comprises five different types of subunit, alpha3, beta3, gamma, delta and epsilon
  • Forms a complex of 9 different subunits
  • The 3 beta subunits have catalytic sites for ARP synthesis
  • Beta subunits are arranged alternately with alpha units like an orange
  • Form a knob like structure held by a stalk of the gamma and epsilon units
  • Delta subunit interacts with the 2 b subunits of Fo
17
Q

what is the theory of rotational catalysts? 5

A
  • 3 beta subunits take it in turns catalysing the synthesis of ATP
  • Any given beta subunit starts in a conformation for binding ADP and Pi
  • The conformation changes so the active site now binds the product ATP tightly
  • Then changes conformation to give the active site a very low affinity for ATP (beta-empty conformation) so ATP is released
  • The gamma subunit rotates (green arrow), and the properties of the beta catalytic subunits change
18
Q

what causes the rotation of the gamma subunit on ATP synthase? 2

A
  • The energy harnessed from the hydrogen ions re-entering the matrix from the intermembrane space
  • The build-up of hydrogen ions means that when they are allowed back in there is enough energy to be harnessed
19
Q

give a summary of energy changes in oxidative phosphorylation?

A
  • Highly exergonic reaction
  • NADH + H+ +1/2 O2  NAD+ + H2O
  • Energy released is coupled to the movement of H+ across the inner membrane
  • Electrochemical energy generated represents temporary conservation of the energy of electron transfer
  • Protons flow spontaneously down their electrochemical gradient releasing energy available to do work
20
Q

for the oxidation of glucose to yield ATP:

  • equation?
  • products and ATP of:
  • glycolysis
  • pyruvate oxidation
  • acetyl CoA oxidation in TCA

total ATP

A

C6H12O6 +6O2 6CO2 + 6H2O + ATP

  • 2NADH, 2ATP,
    3 or 5 ATP depending on the shuttle used
  • 2NADH,
    5 ATP
  • 6NADH, 2fADH2, 2ATP/GTP,
    2 ATP

total ATP= 30/32

21
Q

describe uncoupling reagents? 4

A
  • Normally electron flow and phosphorylation of ATP are tightly coupled
  • Uncouplers dissipate the pH gradient by transporting H+ back into the matrix of the mitochondria so bypassing the ATP synthase
  • Thus an uncoupler severs the link between electron flow and ATP synthesis, with the energy being released as heat
  • This can occur naturally (UCP1, thermogenin, found in brown adipose tissue and has a specific H+ channel through which the proton concentration may be dissipated, allowing energy to be released as heat)
22
Q

describe brown adipose tissue? 4

A
  • High numbers of mitochondria
  • Mitochondria contain thermogenin (UCP-1)
  • Specialised for heart generation
  • Important in new-borns, possible role in obesity/diabetes
23
Q

what is DNP? 6

A
  • exogenous uncoupler
  • Weak acid that can cross cell membranes, ferrying H+ across
  • Each DNP molecule collects a proton from the IMS and moves through the membrane with it, depositing it in the matrix
  • Can then return through the membrane to collect another proton
  • Can die from overdosing on this (people use it for weight loss which they should not do)
  • Toxicity arises from liver damage, respiratory acidosis and hyperthermia

104-theme 2-the liver and regulation of metabolism (19 decks)

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