Mitochondrial Bioenergetics Flashcards
How does pyruvate enter the mitochondria?
MPC
Mitochondrial pyruvate carrier
PDC (PDH) is activated when:
It is DEphosphorylated
Phosphatase Deficiency
PDC is always phosphorylated (inactive). Lactate accumulates leading to lactic acidosis. Mostly affects the CNS.
Regulated reactions of the TCA
- OAA + ACoA –> citrate (citrate synthase)
- Isocitrate –> a-ketoglutarate (isocitrate DH)
- a-ketoglutarate –> succinyl-CoA (a-ketogltarate DH)
Enzymes of reactions that produce NADH, GTP and FADH2 in TCA
- isocitrate DH (NADH)
- a-ketoglutarate DH (NADH)
- succinate thiokinase (GTP)
- succinate DH (FADH2)
- malate DH (NADH)
2 major anaplerotic reactins in the TCA
- Degredation of AAs
2. Carboxylation of pyruvate
2-oxoglutaric aciduria
Rare d/o with development delay and neurological problems in infants.
Metabolic acidosis
Microcephaly
Retardation
Fumarase deficiency
Severe neurological impairment (fatal within 2 yrs of life).
Encephalomyopathy
Dystonia
Auto rec d/o
Increased urinary excretion of TCA intermediates
Mitochondrial depletion syndrome
Hypotonia, dystonia, muscular atrophy, severe sensory impairment.
Inhibitors of complex I
Amytal
Rotenone
Myxothiazol
Piericidin A
Inhibitor of complex II
Malonate
Inhibitor of complex III
Antimycin
Inhibitors of complex IV
CO
Cyanide
H2S
Inhibitor of complex V
Oligomycin
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
Heat produced
Malate-aspartate shuttle
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.
Glycerophosphate shuttle
Works in muscle and brain.
Generates FADH2 into mito matrix.
FADH2 joins ETC at CoQ
Clinical features of mitochondrial diseases (what is affected?)
Nervous system Eyes Skeletal muscle Heart GI Renal
Metabolic features of mitochondrial diseases (3)
Low energy production
Increased free radical production
Lactic acidosis
