Mitochondrial electron transport chain Flashcards
Describe the structure of mammalian mitochondria
Outer membrane - 50/50 protein and lipid, permeable due to porin protein channels
Inner membrane - 76/24 protein and lipid, very impermeable to most polar and/or charged molecules, requiring specific transport proteins, highly invaginated (cristae), enzymes of ETC and ATP-synthase
List four metabolic processes that occur in the mitochondrial matrix
TCA cycle
Fatty acid oxidation
Urea cycle
Pyruvate dehydrogenase complex
Outline the mitochondrial genome
Own genome, DNA and RNA polymerases, tRNAs, and ribosomes
Transcription and translation occur in the matrix
Contain several complete copies of the mitochondrial gemone
How many proteins are encoded by the mitochondrial genome?
13 protein-coding genes
All involved in oxidative phosphorylation
What is the inheritance pattern of mitochondrial mutations?
A mother will pass a defect to all of her children, but a father cannot
The mitochondria comes from the egg (mitochondria in sperm disintegrate before fertilization)
Describe the structures of cytochromes and iron-sulfur centers
Cyotochromes contain heme prosthetic group, iron ion undergoes reversible redox, flips between 2+/3+
Iron-sulfur centers are iron ions complexed to sulfur atoms and to cysteine sulfhydryl groups
Outline of ETC
NADH > Complex I > Coenzyme Q > Complex III > Cytochrome C > Complex IV
Where does proton pumping occur in the ETC?
Complex I (4), complex III (4), and complex IV (2)
Where does the energy to pump protons come from?
The free energy released as electrons pass from one complex to the other
(The reduction potential of each complex in the chain is lower than the previous component)
How is pumping protons related to ATP synthesis?
Pumping protons into the intermembrane space allows for a proton electrochemical gradient to be established, called the proton motive force (PMF). Chemical – proton concentration in intermembrane space is higher than in the matrix. Electrical – cytosolic side of the membrane becomes positive with respect to the matrix side. ATP-synthase utilizes this PMF to generate ATP.
Define the role of succinate dehydrogenase (Complex II)
FAD-containing enzyme, inner membrane, electrons flow from FADH2, through iron-sulcer centers, to coenzyme Q
Describe the role of Electron-transferring flavoprotein (ETF)
matrix, FAD, accept electrons from FAD-containing dehydrogenases, re-oxidizes FADH2 of ETF via ETF-oxidoreductase, passes electrons to coenzyme Q
Describe the role of glycerol 3-phosphate dehydrogenase
outer surface of inner membrane, FAD-containing enzyme, converts glycerol 3-phosphate to dihydroxyacetone phosphate, electrons flow from FADH2 to coenzyme Q
Why does oxidation of 1 mol NADH yield 2.5 mol ATP, yet oxidation of 1 mol FADH2 yields only 1.5 mol ATP?
There are 10 protons translocated for every 1 mol of NADH oxidized, but only 6 protons translocated during oxidation of FADH2
How does rotenone inhibit oxidative phosphorylation?
isolated from woody vine known as derris, inhibits complex I, blocking transfer of electrons from NADH to coenzyme Q
How does antimycin A inhibit oxidative phosphorylation?
isolated from certain spp. Streptomyces, inhibits the reduction of the cytochrome b component of complex II by coenzyme Q, prevents transfer of electrons from coenzyme Q to cytochrome c
How does cyanide inhibit oxidative phosphorylation?
potent inhibitor of complex IV, binds with high affinity to heme iron within cytochrome oxidase, preventing the transfer of electrons from cytochrome c to oxygen
How do uncoupling agents collapse the proton electrochemical gradient?
Provide an alternative pathway for protons to cross the membrane without passing through the ATP synthase complex
No ATP is made, energy is dissipated as heat, and mitochondrion is said to be uncoupled.
2,4-dinitrophenol (DNP) is a protonophore and transports protons across the inner mitochondrial membrane. It cycles catalytically across the membrane, collapsing the gradient.
UCP1 (thermogenin) forms a conductance pathway for protons across the mitochondrial inner membrane, dissipating the energy of the PMF as heat and warming the body
Describe MERRF
Ragged red fibers
Point mutation in a gene that encodes a mitochondrial tRNA for lysine
Severe defect in mitochondrial translation
Describe MELAS
Exercise intolerance, stroke, seizures, ragged red fibers, lactic acidosis
Gene encoding a mitochondrial tRNA for leucine
Describe Leber optic atrophy
Sudden-onset blindness in young adults, death of optic nerve
Chronic energy insufficiency, increased prodution of reactive oxygen species
Genes encoding subunits of complex I
Describe combined oxidative phosphorylation deficiency
Autosomal recessive
Nuclear, rather than mitochondrial DNA
Fatal progressive hepato-encephalopathy
Growth retardation, microcephaly, profound metabolic acidosis, encephalopathy, liver dysfunction
Gene encoding mitochondrial elongation factor G1
