Ch. 13: ETC, Oxidative Phosphorylation, Other O2-Consuming Systems Flashcards
ETC: What is complex I?
NADH-ubiquinone (coenzyme Q) oxidoreductase
ETC: What is complex II?
Succinate-ubiquinone (coenzyme Q) oxidoreductase
ETC: What is complex III?
Ubiquinol (hydroquinone) - cytochrome c oxidoreductase
ETC: What is complex IV?
Cytochrome c oxidase
Which ETC complexes move H+ from mitochondrial matrix ➡️ intermembrane space? How many H+ are moved by each?
Complexes I, III, IV
4 H+
Co-factors in complex I?
FMN
Fe-S
Co-factors in complex II?
FAD
Fe-S
Co-factors in complex III?
Cytochrome b
Fe-S
Cytochrome c1
Co-factors in complex IV?
Cytochrome a (Cu) Cytochrome a3 (Cu) O2
Role of Fe-S (iron-sulfur protein complex Fe4S4)?
Center of accepting & donating e- (complexes I, II, III)
Inhibitors of complex I?
Rotenone
Piericidin A
Amytal
Inhibitors of complex II?
Oxaloacetate
Malonate
Thenoyltrifluoroacetone
Carboxin
Inhibitor of complex III?
Antimycin A
Inhibitors of complex IV?
Cyanide (blocks ferric state iron of cyt a & a3)
CO
Sodium azide
What enzyme complex does NADPH use?
Transdehydrogenase
ATP Synthase: Location of F0 complex? Function?
Inner mitochondrial membrane
Contains H+ pore
ATP Synthase: Location of F1 complex? Function?
Mitochondrial matrix
Contains catalytic activity (ADP + Pi ➡️ ATP)
3 alpha-beta domains of ATP Synthase F1 complex?
Open conformation: ⬇️ affinity for [S] & [P], inactive
Loose conformation: binds loosely, catalytically inactive
Tight conformation: binds tightly, catalytically active
What is the function of uncoupling agents of oxidative phosphorylation?
Create channel ➡️ H+ reenter mitochondrial matrix w/out capturing energy as ATP
Energy released as heat
What are the uncoupling agents of oxidative phosphorylation?
Oligomycin Brown adipocytes (UCP1, thermogenin) 2,4-dinitrophenol ⬆️ aspirin Ionophores (valinomycin, nigericin, gramicidin A)
Of the 2 shuttles moving NADH ➡️ mitochondria, which is principle?
Malate-aspartate shuttle
G3P shuttle: NADH (cytosol) ➡️ FADH2 (MT)
Where does FADH2 go?
Coenzyme Q of ETC
Malate Aspartate shuttle: NADH (cytosol) ➡️ NADH (MT)
Where does NADH go?
Complex I of ETC
Regulation of apoptosis at MT?
➕: Bax, free radicals, ⬆️Ca2+
➖: Bcl2
release of cyt c ➡️ steps to apoptosis?
Cyt c + Apaf-1 + Procaspase 9 ➡️ Apoptosome
Apoptosome + ATP ➡️ activate Caspase 9
Caspase 9 ➡️ activates caspases ➡️ cell death
mtDNA mutations: Nucleotide substitutions
Mildly deleterious base substitutions ➡️ clinical examples?
Familial deafness
Alzheimer’s
Parkinson’s
mtDNA mutations: Nucleotide substitutions
Moderately deleterious base substitutions ➡️ clinical examples?
Leber’s hereditary optic neuropathy (LHON)
Myoclonic epilepsy & ragged-red fiber disease (MERRF)
mtDNA mutations: Nucleotide substitutions
Severe deleterious base substitutions ➡️ clinical examples?
Leigh’s syndrome dystonia
mtDNA mutations: rearrangements
Milder rearrangements (duplications) ➡️ clinical examples?
Maternally inherited adult-onset diabetes & deafness
mtDNA mutations: rearrangements
Severe rearrangements (deletions) ➡️ clinical examples?
chronic progressive external ophthalmoplegia (CPEO)
Kearns-Sayre syndrome (KSS)
lethal childhood disorders
Pearson marrow/pancreas syndrome
Other O2 consuming systems:
Hypoxanthine ➡️ 2 products? (separate rxns w/water & O2 ➡️ also makes ROS)
Xanthine
Uric acid
Other O2 consuming systems:
D-amino acid ➡️ ? (+ H2O2)
Keto acids
Fxn of NADPH producing ROS?
Kills germs
Fxn of glutathione?
Reacts with ROS (protects against O2 toxicity)
Oxidized glutathione (GSSG) reacts with NADPH