6. Mitochondrial Bioenergetics Flashcards
What does “Amphibolic” mean?
Involving both Anabolism and Catabolism
What is the ΔG0’ of Acetyl CoA?
-7.5 kcal/mol
How does pyruvate get into the mitochondria?
A transporter called Mitochondrial Pyruvate Carrier
What complex facilitates the reaction of pyruvate into Acetyl CoA?
Pyruvate Dehydrogenase Complex
What three molecules downregulate pyruvate dehydrogenase complex (PDC)?
- NADH
- ATP
- Acetyl CoA
(All the reasons why we’re doing this reaction in the first place)
Which three steps of the TCA cycle are irreversible and regulatory? What enzymes catalyze them?
- Step 1: Citrate Synthase
- Step 3: Isocitrate dehydrogenase (rate limiting)
- Step 4: α-Ketoglutarate Dehydrogenase
What are the total products of the TCA cycle? (4 things)
- 1x FADH2
- 3x NADH
- 1x GTP
- 2x CO2
What enzyme can hijack the TCA cycle from the start, and what inhibits it to allow the TCA cycle to continue?
- Pyruvate Carboxylase! (Goes into glycolysis)
- Insulin inhibits Pyruvate Carboxylase, allowing the TCA cycle to continue, rather than make more glucose through gluconeogenesis.
What TCA intermediate can be shunted off to make porphyrins like heme?
Succinyl CoA
Where does oxidative phosphorylation occur?
In the inner mitochondrial membrane.
Where does the TCA cycle occur?
In the mitochondrial matrix
Does an agent with a lower Eo’ have a higher or lower affinity for electrons? Does this mean it’s more an oxidizer or a reducer?
Eo’ being low means its affinity for electrons is low. Since Oxidation is Loss, and it has low affinity, we can deduce that low Eo’ is found in reducers (remember that reducers GET oxidized / lose their electrons).
What are the clinical effects of phosphatase deficiency?
Lactic acidosis.
TCA cannot occur because PDC is always phosphorylated. This results in more anaerobic metabolism and more lactate.
At what part of Pyruvate Dehydrogenase Complex do low energy compunds push the reaction forward?
At Pyruvate Kinase
Low energy compounds STOP pyruvate kinase from phosphorylating Pyruvate Dehydrogenase
What 4 TCA enzymes produce reducing power?
- isocitrate dehydrogenase
- alpha-ketoglutarate dehydrogenase
- succinate dehydrogenase
- malate dehydrogenase
(in that order)
Which TCA cycle enzyme produces FADH2?
Succinate Dehydrogenase
What four nasty compounds inhibit Complex 1?
- Amytal
- Rotenone
- Myxothiazol
- Piericidin A
What compound inhibits complex II?
Malonate
What compound inhibits complex III?
Antimycin
What three compounds inhibit complex 4?
- CO (carbon monoxide poisoning)
- Cyanide
- H2S
What is released when uncoupling happens in the mitochondria?
Heat
What complex accepts FADH2?
Complex II
What complex accepts NADH?
Complex I
What is an indicator of mitochondrial damage (in research?)
Cytochrome C levels
(Perepheral membrane protien of the inner mitochondrial membrane)
Shows if the mitochondria is leaking.
What three things can act as uncouplers of the electron transport chain? What are some examples?
- Proton Channels - eg. Thermogenin in brown fat
- Membrane damage - eg. from cytosine arabinoside (AraC - cancer drug) or Azidothymidine (AZT - HIV drug)
- Proton Carriers - eg. 2,4 - Dinitrophenol (DNP) and Asprin
Where does the Malate-Aspartate shuttle enter into the ETC?
Complex 1
Where does the Glycerophosphate shuttle enter into the ETC?
CoQ (Coenzyme Q)
In the Glycerophosphate shuttle, NADH donates electrons to Glycerol 3-Phosphate, which wanders through the outer membrane. What picks those electrons up to transfer them to CoQ?
FADH2
The glycerophosphate shuttle uses FADH2 on the mitochondrial side, whereas the malate aspartate shuttle uses NADH.
