6. Mitochondrial Bioenergetics

Question 1

What does “Amphibolic” mean?

Answer 1

Involving both Anabolism and Catabolism

Question 2

What is the ΔG⁰’ of Acetyl CoA?

Answer 2

-7.5 kcal/mol

Question 3

How does pyruvate get into the mitochondria?

Answer 3

A transporter called Mitochondrial Pyruvate Carrier

Question 4

What complex facilitates the reaction of pyruvate into Acetyl CoA?

Answer 4

Pyruvate Dehydrogenase Complex

Question 5

What three molecules downregulate pyruvate dehydrogenase complex (PDC)?

Answer 5

1. NADH
2. ATP
3. Acetyl CoA

(All the reasons why we’re doing this reaction in the first place)

Question 6

Which three steps of the TCA cycle are irreversible and regulatory? What enzymes catalyze them?

Answer 6

1. Step 1: Citrate Synthase
2. Step 3: Isocitrate dehydrogenase (rate limiting)
3. Step 4: α-Ketoglutarate Dehydrogenase

Question 7

What are the total products of the TCA cycle? (4 things)

Answer 7

1. 1x FADH₂
2. 3x NADH
3. 1x GTP
4. 2x CO₂

Question 8

What enzyme can hijack the TCA cycle from the start, and what inhibits it to allow the TCA cycle to continue?

Answer 8

• Pyruvate Carboxylase! (Goes into glycolysis)
• Insulin inhibits Pyruvate Carboxylase, allowing the TCA cycle to continue, rather than make more glucose through gluconeogenesis.

Question 9

What TCA intermediate can be shunted off to make porphyrins like heme?

Answer 9

Succinyl CoA

Question 10

Where does oxidative phosphorylation occur?

Answer 10

In the inner mitochondrial membrane.

Question 11

Where does the TCA cycle occur?

Answer 11

In the mitochondrial matrix

Question 12

Does an agent with a lower E_o’ have a higher or lower affinity for electrons? Does this mean it’s more an oxidizer or a reducer?

Answer 12

E_o’ being low means its affinity for electrons is low. Since Oxidation is Loss, and it has low affinity, we can deduce that low E_o’ is found in reducers (remember that reducers GET oxidized / lose their electrons).

Question 13

What are the clinical effects of phosphatase deficiency?

Answer 13

Lactic acidosis.

TCA cannot occur because PDC is always phosphorylated. This results in more anaerobic metabolism and more lactate.

Question 14

At what part of Pyruvate Dehydrogenase Complex do low energy compunds push the reaction forward?

Answer 14

At Pyruvate Kinase

Low energy compounds STOP pyruvate kinase from phosphorylating Pyruvate Dehydrogenase

Question 15

What 4 TCA enzymes produce reducing power?

Answer 15

1. isocitrate dehydrogenase
2. alpha-ketoglutarate dehydrogenase
3. succinate dehydrogenase
4. malate dehydrogenase

(in that order)

Question 16

Which TCA cycle enzyme produces FADH₂?

Answer 16

Succinate Dehydrogenase

Question 17

What four nasty compounds inhibit Complex 1?

Answer 17

1. Amytal
2. Rotenone
3. Myxothiazol
4. Piericidin A

Question 18

What compound inhibits complex II?

Answer 18

Malonate

Question 19

What compound inhibits complex III?

Answer 19

Antimycin

Question 20

What three compounds inhibit complex 4?

Answer 20

1. CO (carbon monoxide poisoning)
2. Cyanide
3. H2S

Question 21

What is released when uncoupling happens in the mitochondria?

Answer 21

Heat

Question 22

What complex accepts FADH₂?

Answer 22

Complex II

Question 23

What complex accepts NADH?

Answer 23

Complex I

Question 24

What is an indicator of mitochondrial damage (in research?)

Answer 24

Cytochrome C levels

(Perepheral membrane protien of the inner mitochondrial membrane)

Shows if the mitochondria is leaking.

Question 25

What three things can act as uncouplers of the electron transport chain? What are some examples?

Answer 25

1. Proton Channels - eg. Thermogenin in brown fat
2. Membrane damage - eg. from cytosine arabinoside (AraC - cancer drug) or Azidothymidine (AZT - HIV drug)
3. Proton Carriers - eg. 2,4 - Dinitrophenol (DNP) and Asprin

Question 26

Where does the Malate-Aspartate shuttle enter into the ETC?

Answer 26

Complex 1

Question 27

Where does the Glycerophosphate shuttle enter into the ETC?

Answer 27

CoQ (Coenzyme Q)

Question 28

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?

Answer 28

FADH₂

The glycerophosphate shuttle uses FADH₂ on the mitochondrial side, whereas the malate aspartate shuttle uses NADH.