Dr. Agbas Lecture on Mitochondria Flashcards
Superoxide dismutase does what?
converts superoxide anion into hydrogen peroxide
Glutathionine peroxidase catalase does what
converts free radial hydroxyls into water
ONOO
peroxynitrite free radical nitrogen species
nitrogen oxidation of what gives you free radical nitrogens?
arginine
Ferrooxins (orange correlation box)
small proteins that carry electrons in mitrochondrial P-450 systems
contain iron and sulfur clusters that undergo redox rxns. importantly, Fe3+ –> Fe2+ allows it to be oxidant and reductant
Adrenodoxin
an Fe-2/S2 ferredoxin FDX1
participates in biosynthesis of steroidal hormones
heme synthesis for cytochome c oxidase
metabolism of vitamin D
also involved in plant photosynthesis and metabolism
mito matrix
site of beta oxidation of fatty acids, TCA cycle, urea cycle , ketone body synthesis , Ca2+ resevoir
mito inner membrane
permeable only to CO2, O2, and NH3
mito outer membrane
permeable to small ions as a result of protein channels called “porins”
cytochrome C apoptosis
ctyo-c: mobile carrier between complexes III and IV
apoptotic events lead to formation of “mito permeability transition pore complex” which
activators of caspases when released into matrix
Ubiquinone radical
the intermediate form of Co-Q (Co-Q -1, partially reduced) during transfer of electrons from Complex I to Co-Q, as well as in the transfer from reduced……..Q- can pass electron to O2 to form O2 - (superoxide)
Which complex in the respiratory chain isn’t effected by a mutation in mito DNA?
complex II: it does not encode/contribute any protein to this complex
defects in mito DNA which effect respiratory proteins are associated with what diseases?
midgut carcinoid tumors and other cancers due to increased production of ROS by defective mito
Rotenone
naturally occurring pesticide
used as a natural fish poison for centuries
sunlight destroys it, preventing it from contaminating ground water
moderately toxic to people
inhibits NADH dehydrogenase complex I
Vitamin K3 overcomes inhibition
linked to parkinson disease in cases of chronic exposure
cyanide poisoning
prevents O2 reduction by preventing electron transfer to O2 in terminal step by complex IV
byinds to Fe3+ or reduced form of iron in heme group of complex IV
can be reversed by nitrites: can convert Fe2+ to Fe3+ in hemoglobin causing creation of methemoglobin, which competes for binding in complex IV
THIOSULFATE can cause enzymatic conversion of CN to thiocyanate, which is nontoxic
CN versus CO
CO and NO compete with O2 for binding to the reduced heme group (Fe2+) in complex four.
CN and N3- and H2S bind to oxidized form of heme Fe3+
in what oxidation state does CN bind to the heme group iron?
in what oxidation state does CO bind to the heme group in iron?
Fe3+ — CN
Fe2+ —-CO
heme group in complex IV
Aspirin overdose
doses above 150 mg/kg causes hyperthermia
salicylate uncouples oxidative phosphorylation by disrupting protein gradient across inner mitochondrial membrane. causes dissipation of energy as heat.
stimulates respiratory center in the brain and causes hyperventilation
treatment: hemodialysis and gastric lavage
daily ATP production
free energy from adding Pi to ADP is 7.3 kcal/mol
conversion of food energy into ATP is _____ % efficient
40%
Cytochrome P-450
superfamily of enzymes another example of an electron transfer system that is of high biological relevance
CYP
superfamily of enzymes another example of an electron transfer system that is of high biological relevance
Cytochrome P-450 superfamily
highly active in metabolism of hydrophobic compounds such as steroid hormones, eicosanoids, vitamin D, drugs, toxins etc.
they are “hemoproteins”
how do CYPs work?
essentially, they transfer electrons from NADPH to O2: they transfer one electron to one atom of O which is subsequently incorporated into a protein substrate (R-OH) and another atom to the other atom of O which is reduced to water (H2O)
they catalyze this rxn
NADPH + O2 + R + H —> NADP + ROH + H20
CYPs are ….
“mono-oxidases” and “hemeproteins”
Hypoxia and ATP preservation
lowered O2 —> lowered Res chain activity –> lactate acidosis —> lowered pH in mito —> activation of inhibitory protein IF —> IF binds ATP synthase and prevents from acting in the reverse to hydrolyze ATP
Malate-aspartate shuttle
in heart, liver, and kidneys
because NADH can’t cross mito membrane by itself
steps of the malate-aspartate shuttle
NADH is oxidized in the cytoplasm by transferring two electrons to Malate dehydrogenate (c-MD)
cMD —> crosses mito outer membrane –> as transported across inner membrane while alpha-ketogluterate transported into inner membrane space —> malate oxidized by oxaloacetate, regenerating NADH in the process
oxaloacetate is reduced by glutamate into alpha-ketogluterate and is transferred out as another malate is transferred int. cycle continues
