Electron Transport Chain Flashcards
What is the site of oxidative phosphorylation?
- Electron transport chain in the mitochondria
What is oxidative phosphorylation?
- Mechanism by which most cellular ATP is generated
Describe the structural components of ATP
- Matrix
- Cristae
- Inner membrane
- Intermembrane space
- Outer membrane
What is the use of NADH in the electron transport chain?
- Energy produced by the oxidation of NADH is used by ETC to pump protons into the inter-membrane space of mitochondria
- Electrochemical gradient
What happens when protons released by NADH re-enter the mitochondrial matrix?
- Produce energy
- Used to produce ATP by oxidative phosphorylation
What is actually pumping protons into the inter-membrane space?
- Protein complexes
- Creates EC gradient
How does NADH produced in the cytosol during carbohydrate metabolism cross the inner mitochondrial membrane?
- Glycerol phosphate shuttle
What happens in the glycerol phosphate shuttle?
- Enzyme cytosolic glycerol-3-phosphate dehydrogenase
- Oxidises NADH to NAD and passes electrons to FAD
- Results in reaction: cycle of glycerol 3-phosphate dihydroxyacetone
What happens to the electrons in FADH after the glycerol phosphate shuttle?
- Transferred to Q and Complex III of the ETC
What carries protons and electrons from various sources to ETC?
- NADH and FADH2
Describe how the electrochemical gradient leads to ATP production
- Accumulation of protons follow EC gradient back across membrane through ATP synthase complex
- High to low conc in order to equilibrate
- H+ passes through ATP synthase
- Provides energy for this molecule to produce ATP from ADP + Pi
What is the final electron acceptor?
- Oxygen
- ‘Aerobic’ respiration
What are the first 3 electron transport chain components?
- Complex I- NADH dehydrogenase
- Complex II- Succinate dehydrogenase
- Ubiquinone- Complex Q
Describe what happens at complex I- NADH dehydrogenase
- Accepts electrons from NADH
- Flavoprotein, containing FMN- electron carrier components
- Oxidises mitochondrial NADH to NAD+ and transfers electrons through FMN and iron-sulphur (FeS) complexes to ubiquinone (Q)
- Pumps H+
Describe what happens at complex II-succinate dehydrogenase
- Same enzyme that acts within the TCA cycle
- Flavoprotein that oxidises succinate to fumarate and reduces FAD to FADH2
Describe what happens at ubiquinone- complex Q
- Ubiquitous, mobile, lipid-soluble co-enzyme
- Accepts one electron - half reduced to semiquinone
- Accepts 2 electrons- fully reduced to quinone from complexes I and II and then donates electrons to complex III
- Mobile shuttle
Describe succinate dehydrogenase
- Bound to inner mitochondrial membrane
- Big, bulky enzyme with many subunits
- Oxidises succinate to fumarate (and passes electrons to FAD) as part of TCA cycle and passes these electrons to ubiquinone in mitochondrial electron transport chain
What are the next 4 ETC components (Complex III onwards)?
- Complex III- cytochrome 3 reductase
- Cytochrome C
- Complex IV- cytochrome C oxidase
- Complex V- ATP synthase
What happens at complex III- cytochrome C reductase?
- Reduces cytochrome C and oxidises quinone and takes electrons from ubiquinone
- Electrons are transferred through cytochrome b to an FeS centre then cytochrome C
- And then to cytochrome C
- Pumps H+ ions
What happens at cytochrome C?
- Small haem protein which shuttles electrons one at a time from complex III to complex IV
What happens at complex IV- cytochrome C oxidase?
- Haem-containng dimer which pumps H+ ions to inter membrane space
- Oxidises cytochrome C and conducts electrons through cytochrome a and a3
- Finally reducing oxygen to water
What do iron and copper ions facilitate in the ETC?
- Collection and transfer of 4 electrons
- Reduction of oxygen
What is the reaction that occurs at cytochrome c that produces water?
4 e from cytochrome C +4 H+ + oxygen –> 4 cytochrome C (now oxidised) +2 H2O
Describe the structure of complex V ATP synthase
- Comprises of a motor (F0) embedded in the inner membrane
- And a generator (F1) which extends into the matrix
How efficient if ATP synthase?
- Almost 100%
Makes around 100 ATP molecules per second
What are the three different states of ATP synthase?
- 1st state binds ADP and Pi
- 2nd state synthesised ATP
- 3rd state releases ATP- requires most of proton metic energy
- One complete turn produces 3 ATPs
Describe respiratory control involving ATP synthase
- ADP taken up by mitochondria, ATP synthase stimulated to covert it to ATP
- Acts as signal that a lot energy has been used ip
- Lowers proton gradient and so respiration increases to re-establish proton gradient
- Oxygen uptake declines when conc. of ADP depleted and ATP synthase terminated
What are uncouplers?
- Hydrophobic compounds which can accept protons from the inertmembrane space and then diffuse back into the mitochondrial matrix
What is the consequence of uncouplers?
- Avoid those protons having to go through ATP synthase
- Make inner membrane leaky
- Diminish H+ gradient
- Stimulate respiration as system attempts to restore proton gradient through fuel oxidation
What happens if a gradient cannot be re-established due to continued uncoupling?
- Metabolic energy is wasted as heat
What is dinitrophenol and how does it inhibit oxidative phosphorylation?
- Uncoupler seen to lead to weight loss for munitions making dynamite
- Massive side effects
- Cataracts, blindness, kidney and liver damage and death
- Cells die due to excess heat and lack of ATP
- Sold illegally as a weight loss pill- used legally in herbicides and insecticides
What is rotenone and how does it inhibit oxidative metabolism?
- Common insecticide inhibiting complex I- inhibits oxidation of NADH
What is antimycin and how does it inhibit oxidative metabolism?
- piscicide inhibits the transfer of electrons to Complex III
How do cyanide and carbon monoxide inhibit oxidative metabolism?
- Inhibit complex IV by blocking access of oxygen to cyt-a3
What is oligomycin and how does it inhibit oxidative metabolism?
- Macrolide produced by streptomyces
- Inhibits ATP synthase by blocking its proton channel
- Oxidative phosphorylation of ADP to ATP cannot occur
Give examples of some inhibitors of oxidative metabolism
- Dinitrophenol
- Ronetone
- Antimycin
- Cyanide and CO
- Oligomycin
How many subunits in oxidative phosphorylation are coded for by mtDNA?
13
Give examples of oxidative phosphorylation diseases caused by mutations in mtDNA
- LHON (Leber hereditary optic neuropathy) mutation in NADH dehydrogenase
- Leigh disease (subacute necrotising encephalopathy) mutation in F0 subunits of F0F1-ATPase
What is the consequence of a magnesium deficiency in oxidative phosphorylation?
- ATP readily forms a complex with Mg ion (stabilises it when not used)
- Complex required in all reactions in all reactions requiring ATP
- Deficiency impairs all metabolism because ATP can neither made or used
What is the consequence of an iron deficiency in oxidative phosphorylation?
- Part of iron-sulphur complexes as well as oxygen transport haem systems
What is the consequence of riboflavin dietary deficiency?
- Both FMN and FAD contain it
- Can seriously impair function of these and other flavoproteins
What is the consequence of a copper deficiency?
- Rare in adult but premature infants have low stores
- Impair ATP production by inhibiting terminal ETC reaction
- Leads to pathology of heart where ATP demand is high
- Therefore, dietary preparations for premature babies contain copper
