Mitochondrial Bioenergetics

Question 1

How does pyruvate enter the mitochondria?

Answer 1

MPC

Mitochondrial pyruvate carrier

Question 2

PDC (PDH) is activated when:

Answer 2

It is DEphosphorylated

Question 3

Phosphatase Deficiency

Answer 3

PDC is always phosphorylated (inactive). Lactate accumulates leading to lactic acidosis. Mostly affects the CNS.

Question 4

Regulated reactions of the TCA

Answer 4

1. OAA + ACoA –> citrate (citrate synthase)
2. Isocitrate –> a-ketoglutarate (isocitrate DH)
3. a-ketoglutarate –> succinyl-CoA (a-ketogltarate DH)

Question 5

Enzymes of reactions that produce NADH, GTP and FADH2 in TCA

Answer 5

3. isocitrate DH (NADH)
4. a-ketoglutarate DH (NADH)
5. succinate thiokinase (GTP)
6. succinate DH (FADH2)
7. malate DH (NADH)

Question 6

2 major anaplerotic reactins in the TCA

Answer 6

1. Degredation of AAs

2. Carboxylation of pyruvate

Question 7

2-oxoglutaric aciduria

Answer 7

Rare d/o with development delay and neurological problems in infants.
Metabolic acidosis
Microcephaly
Retardation

Question 8

Fumarase deficiency

Answer 8

Severe neurological impairment (fatal within 2 yrs of life).
Encephalomyopathy
Dystonia
Auto rec d/o
Increased urinary excretion of TCA intermediates

Question 9

Mitochondrial depletion syndrome

Answer 9

Hypotonia, dystonia, muscular atrophy, severe sensory impairment.

Question 10

Inhibitors of complex I

Answer 10

Amytal
Rotenone
Myxothiazol
Piericidin A

Question 11

Inhibitor of complex II

Answer 11

Malonate

Question 12

Inhibitor of complex III

Answer 12

Antimycin

Question 13

Inhibitors of complex IV

Answer 13

CO
Cyanide
H2S

Question 14

Inhibitor of complex V

Answer 14

Oligomycin

Question 15

What occurs when the proton gradient is disrupted?

Answer 15

Uncoupling of P ~ ADP from e- transfer

Protons reenter the matrix

Question 16

When protons reenter the matrix:

Answer 16

TCA and O2 production increase
ATP synthase is inhibited
Heat produced

Question 17

Malate-aspartate shuttle

Answer 17

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.

Question 18

Glycerophosphate shuttle

Answer 18

Works in muscle and brain.
Generates FADH2 into mito matrix.
FADH2 joins ETC at CoQ

Question 19

Clinical features of mitochondrial diseases (what is affected?)

Answer 19

Nervous system
Eyes
Skeletal muscle 
Heart
GI
Renal

Question 20

Metabolic features of mitochondrial diseases (3)

Answer 20

Low energy production
Increased free radical production
Lactic acidosis