(L4) Mitochondrial Bioenergetics

Question 1

What is CK-MB and what is its clinical significance?

L4 LO1

Panini pg. 114, blue box

Answer 1

Phosphorylates creatinine to form phosphocreatinine, an energy storage molecule that replenishes ATP.

CK-MB is found in muslce and brain tissues and can be detected in the blood at elevated levels following an MI.

Question 2

What are the high energy substances produced from the TCA cycle and what is their ATP equivalent?

L4 S6 LO2

Answer 2

• NADH (2.5 ATP)
• FADH₂ (1.5 ATP)
• GTP (1 ATP)

Question 3

What common molecule do fats, carbohydrates, and proteins enter the TCA?

L4 S6 LO2

Answer 3

Acetyl CoA

Question 4

How does pyruvate enter into the mitochondria?

L4 S8

Answer 4

MPC (mitochondrial pyruvate carrier)

Question 5

What is the pyruvate dehydrogenase complex and what are its cofactors?

L4 S9

Answer 5

Trimer:

• E1
• E2
• E3

Cofactors:

• thiamine pyrophosphate (TPP) (E1)
• lipoic acid (E2)
• CoA (E2)
• FAD (E3)
• NAD+ (E3)

Question 6

What is the function of citrate synthase?

L4 S10 LO2

Answer 6

Takes acetyl CoA (2), oxaloacetate (4), and water to make citrate (6).

Question 7

What does aconitase do?

L4 S10 LO2

Answer 7

Converts citrate (6) to isocitrate (6).

Question 8

What does isocitrate dehydrogenase do?

What special feature does this reaction have?

L4 S10 LO2

Answer 8

Dehydrogenates isocitrate (6) to form intermediate of oxalosuccinate which is then is decarboxylated to form α-ketoglutarate (5).

Dehydrogenation converts NAD+ to NADH and H+.

CO2 is produced from decarboxylation.

***rate limiting step***

Question 9

What does α-ketoglutarate dehydrogenase complex do?

What special feature does this reaction have?

L4 S10 LO2

Answer 9

Converts α-ketoglutarate (5) to succinyl CoA (4).

Forms high energy thioester bond.

Decarboxylation produces CO2.

Hydrogen from thiol of CoA converts NAD+ to NADH.

Question 10

What does succinyl CoA synthase do?

What special feature does this reaction have?

L4 S10 LO2

Answer 10

Converts succinyl CoA (4) to succinate (4).

Produces GTP through phosphate level phosphorylation using high energy thioester bond with CoA.

Question 11

What does succinate dehydrogenase do?

What special features does this reaction have?

L4 S10 LO2

Answer 11

Converts succinate (4) to fumarate (4) via dehydrogenation.

Dehydrogenation converts FAD to FADH2.

Enzyme is located in inner mitochondrial membrane.

FADH2 is not released from the enzyme as the electrons are passed to Co-Q (complex 2) in the electron transport chain.

Question 12

What does fumarase do?

L4 S10 LO2

Answer 12

Converts fumarate (4) to L-malate (4) via hydration of double bond.

Question 13

What does malate dehydrogenase do?

L4 S10 LO2

Answer 13

Dehydrogenates malate (4) to form oxaloacetate (4) and H+.

Dehydrogenation converts NAD+ to NADH.

Question 14

What enzymes of the citric acid cycle have regulatory mechanisms?

L4 S9;11 LO2

Answer 14

• pyruvate dehydrogenase
• citrate synthase
• isocitrate dehydrogenase
• α-ketogultarate dehydrogenase

All are inhibited by high [ATP]

Question 15

What is Coenzyme A?

L4 LO3

Panini pg. 123, orange box

Answer 15

Derived from:

• pantothenic acid (vitamin B₅)
• ATP
• cysteine

Used to activate acyl groups (C=O) using high energy thioester linkage

Question 16

What enzynes and molecules regulate pyruvate dehydrogenase activity?

L4 S9 LO4

Answer 16

Phosphorylated PDC is inactive

PDC directly inactivated by:

-Acetyl CoA, NADH

Pyruvate dehydrogenase kinase (PDK), inactivating:

• stimulated by:
• Acetyl CoA, NADH, ATP
• inhibited by:
• CoA, NAD⁺, ADP

Pyruvate dehydrogenase phosphatase (PDP), activating:

• stimulated by:
• Ca²⁺, Mg²⁺

Question 17

What is an anaplerotic reaction and what are the examples of anaplerotic reactions in the TCA cycle?

Under what conditions do they occur?

L4 S13 LO6

Answer 17

Fed conditions:

-carboxylation of pyruvate to form acetyl CoA

Starved conditions:

• degradation of amino acids
• glutamate (Gln/Pro/His/Arg) enters as α-ketoglutarate
• propionyl CoA (intermediate for Thr/Met/Ile/Val) enters as succinyl CoA
• Phe/Tyr/Asp enter as fumarate

Question 18

What citric acid cycle intermediates are used in anabolic functions and what are they used to generate?

L4 S14 LO6

Answer 18

Citrate:

-fatty acids/isoprenoids

Malate:

-glucose

α-ketoglutarate:

-certain AAs

Oxaloacetate:

-certain AAs

Question 19

What is the significance of thymaine (vitamin B₁) deficiency?

L4 LO4

Panini pg. 129, blue box

Answer 19

Thyamine is used to make TPP which is a cofactor in PDC and α-ketoglutarate dehydrogenase.

Nutritional deficiency is called Beriberi.

Wernicker-Korsakoff syndrome is a deficiecny due to poor absorption as a result of alcoholism.

Question 20

What effect does citrate have on enzyme function?

L4 LO5

Panini pg. 130, orange box

Answer 20

Citrate is indiciative of an ATP-rich state.

It inhibits PFK to prevent further production of ATP.

It activates acetyl CoA carboxylase promoting storage of energy as fat.

Question 21

What are the differnt methods of uncoupling and what are examples?

L4 S35 LO11

Answer 21

Membrane damage:

• AraC
• AZT

Proton carriers:

• DNP
• Aspirin

Proton channels:

-UCP-1

Question 22

How does NADH enter the mitochondria?

L4 S38-40 LO12

Answer 22

NADH is not permeable so it must be converted, transported, and then regenerated via…

Malate-aspartate shuttle (heart, liver, and kidneys)

Glycerophosphate shuttle (muslce and brain)

Question 23

What is Luft’s disease?

L4 S42-44 LO13

Answer 23

Excessive uncoupling of oxidative phosphorylation resulting in dramatically increased BMR