Electron Transport Chain Flashcards
What do the cristae of the mitochondria contain?
Enzymes of electron transport chain and ATP synthesis
Mitochondrial Genome
Genome small and circular
Encodes only 13 proteins of respiratory chain
How are mitochondrial mutations inherited?
Inherited exclusively in maternal manner
Mothers pass any mitochondrial mutation to all their children
Fathers do not transmit the mutation
Electron Transport Chain
Sequence of electron carriers found on cristae of the inner mitochondrial membrane
Electrons pass from carrier to carrier - carrier becomes reduced as electrons are accepted and re-oxidized as electrons pass to next carrier in line
Energy released as heat
Some energy trapped through synthesis of ATP
What are the 2 families of iron containing proteins?
- Cytochromes
- Iron-Sulfur Proteins
What do cytochromes contain? What happens to associated iron ion?
Heme prosthetic group
Associated ion reversibly oxidized and reduced - flips between Fe2+ and Fe3+
What do iron-sulfur proteins contain?
Iron-Sulfur Centers from complex III of respiratory chain
Coenzyme Q
Non-protein electron carrier
Also known as ubiquinone
Lipid soluble
Can be reduced in stages
Give overview of electron transport chain
- Electrons pass from NADH through Complex I to Coenzyme Q
- Electrons pass from Coenzyme Q to Complex III
- Electrons pass from Complex III to cytochrome c
- Electrons from cytochrome c pass to Complex IV
- Complex IV uses electrons to reduce oxygen to water
How does reduction potential change in electron transport chain? Why?
Reduction potential of each complex is higher than preceding complex
Free energy released by electron transfer trapped by pumping protons from matrix into intermembrane space
How are complex I, III, and IV arranged in membrane?
Vectorial Arrangement
Electrons and protons received on matrix side and protons release on intermembrane space side
Proton electrochemical gradient
Inner membrane of mitochondria is highly impermeable to protons, but minor proton leak creats electrochemical gradient
Chemical - Higher proton conc in intermembrane space than in matrix
Electrical - outer face of inner membrane becomes positive with respect to matrix face
Potential energy from driving H+ back to matrix used to make ATP
ATP synthase
F0 spans membrane - form proton pore so protons can go back into matrix
F1 projects into matrix and catalyzes phosphorylation of ADP to ATP
Proton entry coupled to rotation of F1
What inhibits ATP synthase?
Oligomycin - blocks proton channel
Complex I of Electron Transport Chain
NADH:Coenzyme Q oxidoreductase
Contains several FMN containing proteins and iron-sulfur proteins
Catalyzes reaction of
NADH + H+ + Coenzyme Q –> NAD+ + Coenzyme Q-H2
Complex III of Electron Transport Chain
Cytochrome b-c1 complex
Contains cytochromes b and c1 plus an iron-sulfur protein
Passes e- from coenzyme Q to cytochrome c
Complex IV of Electron Transport Chain
Cytochrome c oxidase
Contains copper ions and cytochromes a and a3
Electrons pass from cytochrome c through copper ions and cytochromes to oxygen
High affinity for oxygen
What is involved in delivering electrons from FADH2 to coenzyme Q? What do they not involve?
- Succinate dehydrogenase
- Electron-transferring flavoprotein (ETF)
- Mitochondrial glycerol 3-phosphate dehydrogenase
Do not involve proton pumping!
Succinate dehydrogenase
FAD containing enzyme for TCA cycle
Associated with inner membrane of mitochondria
Forms complex II of ETC - electrons flow from FADH2 to Coenzyme Q
Electron Transferring Flavoprotein (ETF)
Soluble protein of mitochondrial matrix
Contains FAD
Can accept electrons from other FAD dehydrogenases
ETF oxidoreductase - reoxidizes FADH2 of ETF and passes e- on to coenzyme Q
Mitochondrial glycerol 3-phosphate dehydrogenase
FAD containing enzyme
Coverts glycerol 3-phosphate to dihydroxyacetone phosphate
Electrons flow from FADH2 to coenzyme Q
What inhibits the electron transport chain?
Anoxia
Rotenone
Antimycin A
Cyanide
How does Anoxia inhibit electron transport chain?
no oxygen, no oxidative phosphorylation
How does Rotenone inhibit electron transport chain?
Inhibits complex I, block electron transfer from NADH to coenzyme Q
How does Antimycin A inhibit electron transport chain?
inhibits complex III, blocks electrons transfer from coenzyme Q to cytochrome C
How does cyanide inhibit electron transport chain?
inhibits complex IV, binds heme iron in complex and blocks electron transfer from cytochrome c to oxygen
What are uncouplers?
Uncoupling agents short circuit mitochondria and pathway of proton flow bypasses ATP synthase
Usually protons enter mitochondrial matrix through ATP synthase and re-entry is coupled to synthesis of ATP
2,4-dinitrophenol (DNP)
Potent uncoupling agent that was marked as dietary supplement. Still used for weight loss
Anionic form - drawn to positive side and picks up proton
Neutral form - drawn to alkaline side and release proton
Catalytic cycle collapses proton gradient
What is the role of brown adipose tissues and what protein does it express?
Brown because of high prevalence of mitochondria and main role is to generate heat rather than ATP –> important for non-shivering thermogenesis
Express protein UCP1 (uncoupling protein 1) that forms proton conductance pathway where protons can bypass ATP synthase and energy is dissipated as heat
How is ATP delivered to cytoplasm?
ATP-ADP translocase moves ATP to cytoplasm and ADP into the matrix
Phosphate carrier catalyzes either symport of Pi and a proton or antiport of OH- and Pi
What occurs generally with defects in oxidative phosphorylation?
Often impact muscles and nerves - tissues with high energy demand
Mitochondrial encephalomyopathies
MERRF
Defect in oxidative phosphorylation
Myoclonic epilepsy associated with ragged red fibers
Most due to point mutations in mitochondrial tRNA for lysine
MELAS
defects in oxidative phosphorylation
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
Common mutations in mitochondrial gene encoding tRNA for leucine
Combined oxidative phosphorylation
Defects in oxidative phosphorylation
Autosomal recessive inheritance - nuclear genes impacted
Combined oxidative phosphorylation deficiency 1 - mutation in mitochondrial elongation factor 1 gene
Combined oxidative phosphorylation deficiency 2 - mutation in mitochondrial ribosomal protein S16