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2 parts of oxidative phosphorylation

8 electrons on electron carriers (1 FADH2 and 3NADH)- making ATP is a 2 step process
1) Donate electrons to ETC- proteins/ lipid like molecules sitting on the inner mitochondrial membrane
As e- go down the ETC they loose energy- used to pump H+ across the inner mitochondrial membrane into intermembrane space
2) Go down diffusion gradient through ATP synthase complex (producing ATP)


What does the term tightly coupled mean?

- Electrons going through the ETC is very tightly linked to ATP synthesis
- Uncouples interfere in this process
-Need intact mitochondria for this process to work efficiently


Explain ETC in more detail

4 protein complexes (I-IV)- 3 proton pumps at (I,III,IV) and 1 link to the TCA cycle (II)
- 2 small components (fully removable)- CoQ, cytochrome C
1) Complex I- NADH dehydrogenase- NADH binds releasing 1e- pair, transfers via no channels to CoQ (Via domains within complex 1 FMN (flavin mono-nucleotide) and Fe- S (iron- sulphur proteins) helps transfer electrons to CoQ)
- Reduction in free energy- free energy released sufficient to allow some proteins to be pumped out via mitochondrial membrane
So we generate ATP from it
Regeneration NAD
2) Complex II- succinate hydrogenase- Enzyme within TCA cycle imbedded within mitochondrial membrane,
FADH2 directly produced from TCA cycle- so doesn't need to bind
Electrons from FADH2 transferred to CoQ vis Fe-S proteins
So electrons from both complex I and II to CoQ
3) CoQ/ ubiquinone (ubiquitous in animals and many bacteria)- small lipid hydrophobic ubiquinone, in high conc in IMM, transfers e- to complex III
- Complex III- cytochrome C reductase- Transport e- from CoQ to cytochrome C and pumps some H+ across, Heme prosthetic group (containing iron within porphyrin ring)
Cytochrome C- peripheral membrane protein loosely bound to complex III transferring e- to complex IV, highly conserved between eukaryotes (similar sequence funghi as v important)
- Complex IV(cytochrome C oxidase)- 13 protein subunits, 2 here groups and 3 Cu ions. Transfers e- from cytochrome C to oxygen atom to make H2O, pumps many protons across IMM


Why is the regeneration of NAD important

- Needed for TCA cycle a keto-gluconate dehydrogenate reactions (and others) require NAD
- If NAD not supplied then cells stop producing ATP due to lack of electron carriers
- During exercise/ lack O2- Use the pyruvate to lactate reaction to regenerate NAD for glycolysis


Why are the electrons transferred

Accepting carrier has higher affinity for electrons than the donating carrier- creating a redox potential which drives transfer e-
Also delta G very -ve- favourable reaction


Outline ATP synthase/ complex V

Composed 2 subunits
F1ATPase- generates ATP
F0coupling factor- protein channel spanning IMM
- Protons pass down channel towards matrix through F0, causing C ring of F0 to rotate, causing conformational change in b- subunit of F1 so it can now bind ADP and Pi to release ATP


Explain ATP yield

Theoretically 6-7 ATP per electron pair yet in reality only see
3 (2.5) e- from NADH
2 (1.5) from FAHD2
These are the P/O ratios- no ATP per O atom
NADH higher as supplies electrons to complex I II and IV, FADH2 to complex III and IV


Agents affecting oxidative phosphorylation

- ATPase inhibitors- oligomycin
- Specific site inhibitors of ETC
- Uncouplers- neutralise proton gradient preventing ATP synthesis


Nane some specific site inhibitors of ETC

- complex I (rotenone, amytal)- wont cause death as still able to generate e- gradients via complex III and IV via FADH2 binding to complex II
- Complex III- antimycin A
- Complex IV cyanide, azide, CO
These are deadly
- Link between rotenone. mitochondrial disfunction and parkinsons?


Explain uncouplers in more detail

Chemicals/ protons in the body that dissipate the proton gradient
Allow electron transport to occur
Protons are pumped into the intermembrane space
Don't go through the ATP synthase channels (destroy H+ gradient) so no ATP produced

Hence uncoupling ATP synthesis from ETC
- caused by chemicals (dinitrophenol) and natural- uncoupling proteins (UCPs)
- UCP1- thermogenin- found in mitochondria of brown adipose tissue- energy from ETC used to generate heat- new borns and hibernation
- UCP3- skeletal muscle- regulate body weight- makes mice resistant to diet induced obesity as ATP converted to heat not fat