Flashcards in Mitochondrial Bioenergetics Deck (20):
How does pyruvate enter the mitochondria?
Mitochondrial pyruvate carrier
PDC (PDH) is activated when:
It is DEphosphorylated
PDC is always phosphorylated (inactive). Lactate accumulates leading to lactic acidosis. Mostly affects the CNS.
Regulated reactions of the TCA
1. OAA + ACoA --> citrate (citrate synthase)
3. Isocitrate --> a-ketoglutarate (isocitrate DH)
4. a-ketoglutarate --> succinyl-CoA (a-ketogltarate DH)
Enzymes of reactions that produce NADH, GTP and FADH2 in TCA
3. isocitrate DH (NADH)
4. a-ketoglutarate DH (NADH)
5. succinate thiokinase (GTP)
6. succinate DH (FADH2)
8. malate DH (NADH)
2 major anaplerotic reactins in the TCA
1. Degredation of AAs
2. Carboxylation of pyruvate
Rare d/o with development delay and neurological problems in infants.
Severe neurological impairment (fatal within 2 yrs of life).
Auto rec d/o
Increased urinary excretion of TCA intermediates
Mitochondrial depletion syndrome
Hypotonia, dystonia, muscular atrophy, severe sensory impairment.
Inhibitors of complex I
Inhibitor of complex II
Inhibitor of complex III
Inhibitors of complex IV
Inhibitor of complex V
What occurs when the proton gradient is disrupted?
Uncoupling of P ~ ADP from e- transfer
Protons reenter the matrix
When protons reenter the matrix:
TCA and O2 production increase
ATP synthase is inhibited
Works in heart, liver and kidneys.
Generates NADH into mito matrix.
NADH joins ETC at complex I.
e- transferred to malate (which enters mito) gives up NADH and converts to aspartated which leaves mito and becomes malate.
Works in muscle and brain.
Generates FADH2 into mito matrix.
FADH2 joins ETC at CoQ
Clinical features of mitochondrial diseases (what is affected?)