5.2: Electron Transport And Oxidative Phosphorylation

Summary

In summary, energy is needed for cells to perform the functions that they must carry out in order to stay alive. At its most basic level, this means fighting a continual battle with entropy, but it is not the only need for energy that cells have.

References

1. Winge, D.R., Mol Cell Biol. 2012 Jul; 32(14): 2647–2652. doi: 10.1128/MCB.00573-12

Energy: Electron Transport & Oxidative Phosphorylation

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Figure 5.14 - Overview of electron transport (bottom left and top right) and oxidative phosphorylation (top left - yellow box) in the mitochondrion

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Figure 5.15 - Loss of electrons by NADH to form NAD+. Relevant reactions occur in the top ring of the molecule.

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Figure 5.16 - Flow of electrons from NADH into the electron transport system. Entry is through complex I

Image by Aleia Kim

Figure 5.17 - Flow of electrons from FADH2 into the electron transport chain. Entry is through complex II.

Image by Aleia Kim

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Figure 5.18 - Complex I embedded in the inner mitochondrial membrane. The mitochondrial matrix at at the top

Wikipedia

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Figure 5.19 - Complex II embedded in inner mitochondrial membrane. Matrix is up.

Wikipedia

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Figure 5.20 - Movement of electrons through complex I from NADH to coenzyme Q. The mitochondrial matrix is at the bottom

Image by Aleia Kim

Figure 5.21 - Movement of electrons from succinate through complex II (A->B->C->D->Q). Mitochondrial matrix on bottom.

Image by Aleia Kim

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Figure 5.22 - Complex II in inner mitochondrial membrane showing electron flow. Matrix is up.

Wikipedia

Figure 5.23 - Coenzyme Q

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Movie 5.2 - The Q-cycle

Wikipedia Figure 5.24 - The Q-Cycle Image by Aleia Kim

Figure 5.24 - Complex III

Wikipedia

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Figure 5.25 - The Q-cycle. Matrix is down.

Image by Aleia Kim

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Figure 5.26 - Movement of electrons and protons through complex IV. Matrix is down

Image by Aleia Kim

Figure 5.25 - Cytochrome c with bound heme Group

Wikipedia

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Figure 5.27 - Mitochondrial anatomy. Electron transport complexes and ATP synthase are embedded in the inner mitochondrial membrane

Image by Aleia Kim

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Figure 5.28 - ATP synthase. Protons pass from intermembrane space (top) through the complex and exit in the matrix (bottom).

Image by Aleia Kim

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Movie 5.3 - ATP Synthase - ADP + Pi (pink) and ATP (red). The view is end-on from the cytoplasmic side viewing the β subunits Movie 5.3 - ATP Synthase - ADP + Pi (pink) and ATP (red). The view is end-on from the cytoplasmic side viewing the β subunits

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Figure 5.29 - Important structural features of the ATP synthase

Image by Aleia Kim

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Figure 5.30 - Loose (L), Tight (T), and Open (O) structures of the F1 head of ATP synthase. Change of structure occurs by rotation of γ-protein (purple) in center as a result of proton movement. Individual α and β units do not rotate

Image by Aleia Kim

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Figure 5.31 - Respiration overview in eukaryotic cells

Wikipedia

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Rest

ATP High / ADP Low

Oxidative Phosphorylation Low

Electron Transport Low

Oxygen Use Low

NADH High / NAD+ Low

Citric Acid Cycle Slow

Exercise

ATP Low / ADP High

Oxidative Phosphorylation High

Electron Transport High

Oxygen Use High

NADH Low / NAD+ High

Citric Acid Cycle Fast

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Figure 5.32 - Three inhibitors of electron transport

Image by Aleia Kim

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Figure 5.33 - Oligomycin A - An inhibitor of ATP synthase

Figure 5.34 - 2,4 DNP - an uncoupler of respiratory control

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In Cells With Tight Coupling

O2 use depends on metabolism NAD+ levels vary with exercise Proton gradient high with no exercise Catabolism depends on energy needs ETS runs when OxPhos runs and vice versa

In Cells That Are Uncoupled

O2 use high NAD+ Levels high Little or no proton gradient Catabolism high OxPhos does not run, but ETS runs rapidly

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Figure 5.35 - Alternative oxidase (AOX) of fungi, plants, and protozoa bypasses part of electron transport by taking electrons from CoQ and passing them to oxygen.

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Figure 5.36 - Structure of an oxygen free radical

Wikipedia

NADPH + 2O2

NADP+ + 2O2− + H+

Figure 5.37 - Three sources of reactive oxygen species (ROS) in cells

Wikipedia

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Figure 5.38 A hydroxyl radical

Wikipedia

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Reduced Glutathione (GSH) + H2O2

Oxidized Glutathione (GSSG) + H2O

Figure 5.40 - Detoxifying reactive oxygen species

Figure 5.39 - Catalase

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1. O2- + Enzyme-Cu++

O2 + Enzyme-Cu+

2. O2- + Enzyme-Cu+ + 2H+

H2O2 + Enzyme-Cu++

Figure 5.41 - SOD2 of humans

Figure 5.42 3 - Peroxynitrite Ion

Figure 5.44 - SOD1 of humans

Wikipedia

Figure 5.45 - SOD3 of humans

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Figure 5.43 - Peroxynitrite’s effects on cells lead to necrosis or apoptosis

Wikipedia

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RH + O2 + NADPH + H+

ROH + H2O + NADP+

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Figure 5.46 - Cytochrome c with its heme group

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Figure 5.47 - Fe2S2 Cluster

Figure 5.48 - Redox reactions for Fe4S4 clusters

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Figure 5.49 - Tyramine

Figure 5.50 - Phenethylamine

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Figure 5.51 - Guanine and 8-oxo-guanine

Figure 5.52 - Adenine-8-oxo-guanine base pair. dR = deoxyribose

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Figure 5.53 - Good antioxidant sources

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Figure 5.55 - Oxidized glutathiones (GSSG) joined by a disulfide bond

Wikipedia

Figure 5.54 - Structure of reduced glutathione (GSH)

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Figure 5.56 - Resveratrol

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I'm a little mitochondrion​ Who gives you energy​ I use my proton gradient​ To make the ATPs​ ​ He's a little mitochondrion​ Who gives us energy​ He uses proton gradients​ To make some ATPs​ ​ Electrons flow through Complex II​ To traffic cop Co-Q​ Whenever they arrive there in​ An FADH-two​ ​ Electrons flow through Complex II​ To traffic cop Co-Q​ Whenever they arrive there in​ An FADH-two

Tightly coupled is my state​ Unless I get a hole​ Created in my membrane by​ Some di-ni-tro-phe-nol​ ​ Yes tightly coupled is his state​ Unless he gets a hole​ Created in his membrane by​ Some di-ni-tro-phenol​ ​ Both rotenone and cyanide​ Stop my electron flow​ And halt the calculation of​ My "P" to "O" ratio​ ​

Recording by Tim Karplus

Lyrics by Kevin Ahern Recording by Tim Karplus Lyrics by Kevin Ahern

I’m a Little Mitochondrion

To the tune of “I’m a Lumberjack”

Metabolic Melodies Website HERE

In the catabolic pathways that our cells employ​ Oxidations help create the ATP​ While they lower Gibbs free energy​ Thanks to enthalpy

If a substrate is converted from an alcohol​ To an aldehyde or ketone it is clear​ Those electrons do not disappear​ They just rearrange – very strange​ ​ N-A-D is in my ears and in my eyes ​ Help-ing mol-e-cules get oxidized​ Making N-A-D-H then

And the latter is a problem anaerobically​ ‘Cuz accumulations of it muscles hate​ They respond by using pyruvate​ To produce lactate​ ​ Catalyzing is essential for the cells to live​ So the enzymes grab their substrates eagerly​ If they bind with high affinity​ Low Km you see, just as me​ ​ N-A-D is in my ears and in my eyes ​ Help-ing mol-e-cules get oxidized​ Making N-A-D-H then

N-A-D

To the tune of “Penny Lane”

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Recorded by Tim Karplus

Lyrics by Kevin Ahern Recorded by Tim Karplus Lyrics by Kevin Ahern

When oxygen’s electrons all are in the balanced state

There’s twelve of them for oh-two. The molecule is great

But problems sometimes happen on the route to complex IV

Making reactive species that the cell cannot ignore

Oh superoxide dismutase is super catalytic

Keeping cells from getting very peroxynitritic

Faster than a radical, its actions are terrific

Superoxide dismutase is super catalytic

Enzyme, enzyme deep inside

Blocking all the bad oxides

The enzyme’s main advantage is it doesn’t have to wait

By binding superoxide in a near-transition state

It turns it to an oxygen in mechanism one

Producing “h two oh two” when the cycle is all done

Oh superoxide dismutase you’re faster than all them

You’ve got the highest ratio of kcat over KM

This means that superoxide cannot cause too much mayhem

Superoxide dismutase is faster than all them

Superoxide dismutase

Stopping superoxide’s ways

The enzyme’s like a ping-pong ball that mechanistic-ly

Bounces between two copper states, plus one and two you see

So S-O-D behaves just like an anti-oxidant

Giving as much protection as a cell could ever want

Oh superoxide dismutase, the cell’s in love with you

Because you let electron transport do what it must do

Without accumulation of a radical oh two

Superoxide dismutase - that’s why a cell loves you

Superoxide Dismutase

To the tune of “Supercalifragilistiexpialidocious”

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Lyrics by Kevin Ahern

No Recording Yet For This Song