Dr. Agbas' Mitochondria lecture Flashcards
Electron only transfer
electrons are transferred between two metal ions
Reducing Equivalent
Involves transfer of both proton and electron
Eo =
Redox potential, measure of affinity of a redox pair of electrons
High Eo =
high affinity of a redox pair of electrons
Low Eo =
low affinity of a redox pair of electrons
OxPhos
oxidative phosphorylation
Mechanism of OxPhos:
must do the following for key goals
1) transfer electrons from NADH and FADH2 to O2
2) To establish a proton gradient across the inner mitochondrial membrane
3) to synthesize ATP
OxPhos is mediated by the
respiratory chain integral proteins
Cytochrome C
PEripheral receives electrons from complex III and IV
important because if mito becomes leaky, CytoC in the cytosol will signify apoptosis
CoQ (ubiquinone)
freely mobile a lipophilic molecule, not a prosthetic group-complex III
what is measuring cytochome C useful for?
a biomakrer of membrane well being
Which has a higher redox potential: O2 or NAD+?
O2
Gibbs and redox potential are related how
G = -nF delta Eo direct
what kind of ratio/relationship does Gibbs free energy have to redox potential?
a direct, but negative
the higher the G the
more negative the E
Redox pairs vs redox couples
pairs are molecule that can exchange electrons and protons (two molecules)
couples are metals than can just exchange electrons
how many proteins are in the respiratory chain?
5
Which proteins in the respiratory chain pump protons into the inner membrane space?
1, 3, 4
which protein complex pumps proteins back into the mito cytoplasm?
5
SOD1:
superoxide dismutase 1, found in cytoplasm and has Mn as a prosthetic group
SOD2
superoxide dismutase 2, found in innermembrane space and has ZnCu as prosthetic groups
Free radicals: are they useful?
yes, some serve as signaling molecules (For example, in the mitochondrial fusion)
Mitochondrial encephalopathy, lactic acidosis, and stroke is connected to defects in complexes….
What are symptoms?
Complex I, IV
Muscle weakness and pain
acumulation of lactic acid, vomiting, loss of appetite, seizures, strokelike episodes
onset: infancy to early childhood
Kearns-Sayre syndrome: affected ETC complexes
symptoms?
All complexes
eye pain, retinopathy, apthalmoplegia, ptosis, ragged red fibers. onset before 20. cardiac conduction,
Leber hereditary optic neuropathy
complexes I, III
degenerative optic nerve
continued loss of central vision
early adulthood onset
Leigh syndrome
complex I and IV
Difficulty swallowing, weak motor skills, vomiting, lesions in basal ganglia and brainstem
onset: first year of life
pmf
proton motive force
what two factors constitute a proton motive force across Complex V?
Vm and pH
What drives ATP synthesis across complex V?
membrane potential and pH
chemiosmosis =
oxidation of substrates coupled to ADP phosphorylation
O2 consumed depends on
ADP added
Uncoupling, i.e. disruption of proton gradient
name 4 things that occur
TCA cycle is accelerated
electron transfer to O2 increases
heat generation
Synthesis of ATP is accomplished by what complex?
ATP synthase
catalyzed by a large membrane bound protein
7.3 kcal/mol to form ATP
inhibitors of ATP synthase
oligomycin disrupts proton transport through channe l
high ATP/ADP ratio does what
inhibits ATP synthase increases H gradient Decreases electron transport/ H pumping slows down TCA cycle decreases glycolysis
Low ATP/ADP ratio
activates ATP synthase decreases H gradient increases electron transport H pumping accelerates TCA cycle increases glycolysis
Ubiquinone receives electrons from complexes
I and II, and it delivers to II
cytochrome C transfers electrons between
III and IV
ROS production occurs at what points in the ECT?
between I and II, between III and IV
ATP synthase =
ATP synthasome
Malate asparatate shuttle
operates in the heart, liver, and kidney
helps NADH enter the ETC at Complex 1
malate is oxidized while reducing NAH–> NADH
the oxidized malate (oxaloacetate) is reduced by glutamate to alpha-ketogluterate
Glycophosphate shuttle
operates in skeletal muscle and brain helps FADH(2) donate its electron to the ETC at CoQ
What inhibitors block Complex I?
Amytal
Rotenone
Myoxthiazol
Piericidin A
What inhibitors block complex II?
malonate
What inhibitors block complex III?
antimycin
what inhibitors block complex IV?
CO
Cyanide
H2(S)
what inhibitors block complex V?
oligomycin
where does FADH2 come into the ETC compared to NADH?
NADH - complex 1
FADH2 - complex 2
which complex passes electrons to O2?
IV
