BioChem: METC
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- In the electron transport chain, what does it do overall in terms of reoxidizing?
- -it reoxidizes the coenzymes reduced in glycolysis and the TCA cycle
- What are the 4 complexes of the ETC?
-
1) NADH-Ubiquinone Oxidoreductase
2) Succinate - Ubiquinone Oxidoreductase
3) Ubiquinol - Cytochrome C Oxidoreductase
4) Cytochrom C Oxidase - How are electrons passed through Complex 1?
-
-elctrons from NADH to FMN
-then to a series of Fe-S proteins
-Lastly passed to Ubiquinone -
How many electrons can NADH carry?
FMN?
Fe-S proteins?
Ubiquinone? -
-2
-1 or 2
-1
-2 - What are the two possible centers of Iron-Sulfate proteins?
- -2FE-2S or 4Fe-4S complexes
- What was the case of 'Living Statues"?
-
-Heroin users who used a certain synthetic heroin became frozen with advanced stages of Parkinsons Disease
-this was from MPTP in the synthetic being converted to MPP
-MPP attacked the substantia nigra degrading the cells rapidly - Describe MPP in the body.
-
-a powerful inhibitor of Complex I in the mitochonrial ETC
-attacks the substantia nigra part of the brain
-Parkinson's patients have the same deterioration, but much slower - What is dopamines role in Parkinson treatment?
-
-brain cells can no longer produce dopamine, so injections can be given to provide it
-it allows for smooth muscle control/movement. w/o it, muscles are rigid and hard to control - What is Complex II also known as?
- -Succinate Dehydrogenase (from TCA cycle)
- Describe what Complex II does?
-
-contains a covalentrly bound FAD and two Fe-S proteins
-also transfers electrons to Ubiquinone (like C-I) - Describe Complex III.
- -passes electrons from reduced Ubiquinone to Cytochrome C
- What are cytochromes?
-
-small membrane associated proteins with a heme
--different classes have different substitutions on the heme group - Spectromphotomically, how can you tell cytochromes apart?
- -when reduced, they have different absorbancies
- What does Complex IV do?
-
-transfers electron from Cytochrome C to Oxygen
-three largest proteins are coded for in the mitochondrial DNA
-these three proteins contain the copper ions and two iron cofactors (cytochromes a and a3) - How many electrons does the reduction of Oxygen require?
-
-4 electrons
*copper and heme iron can only handle 1 electron - What are the parts 1 and 2 (of 4) of the Chemiosmotic Hypothesis?
-
1) mitochondrial inner membrane (MIM) is impermeable to H+
2) MIM has carrier proteins to mediate entry/exit of metabolites - What is part 3 of the Chemiosmotic Hypothesis?
- 3) ETC is proton-translocating and pumps H+ out of matric space when electrons are transported
- What is the 4th part of Chemiosmotic Hypothesis?
- 4) mitochondrial ATP synthase complex also translocates protons across membrane. It can use the energy of proton gradient to drive ATP synthsis
- What are 4 peices of evidence for the Chemiosmotic theory?
-
- mit. membranes can establich proton gradient
- intact MIM is required for oxidative phosphorylation
- key electron transport proteins spand the inner membrane
- Uncouplers act by dissipating the proton gradient - In respiration of mitochondria, what two things are coupled?
-
-oxidation of substrates
-phosphorylation of ADP - What must be present for respiration to proceed in Mitochonrion?
-
-ADP must be present
*amount of O2 consumed depends upon the amount of ADP added - What does Uncoupler DNP do?
- -allows for O2 consumption without ADP
- Describe Uncouplers.
-
-allow for O2 consumption without ADP
-lipid-soulbe weak acids
-can cross MIM
-deplete any proton gradient by transporting protons across the membrane - Give an example of a common Uncoupler.
- -2.4-Dinitrophenol
- Why can both acidic and Basic forms of DNP dissolve in the membrane?
- -becuase negative charge is delocalized over the ring
- What is Mitochondrial Inner Membrane ATPase for?
-
-treatment on inside-out particles to give free F1
-Part remaining in membrane is F0 - What does F1 do?
- -hydrolizes ATP (can NOT synthesize ATP)
- What does F0 do?
- -catalyze proton transport (can NOT synthesize ATP)
- What does F1F0 ATPase do?
- -Haloenzyme that uses proton motive force to convert ADP back to ATP
- What are two Mitochondrial diseases?
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-Leber's Hereditary Optic Neurophothy (LHON)
-Mutations in Cytochrome b - Describe Hereditary Optic Neurophathy (LHON).
-
-causes sudden-onset blindness
-mutation in mitochondrial DNA for proteins in electron transport complex I
-can cause dystonia - Describe mutations of Cytochrome b.
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-exercise intolerance, lactic acidosis in resting state and myoglobinuria
-somatic mutation in the gene for cytochrome B