Question 1

Which of the following best explains why malate oxidation to oxaloacetate can proceed in the mitochondria despite having a positive standard free energy change ($$\Delta G$$^{\circ\prime}$$ \u003e 0$$)?

Accepted Answer

Low concentrations of oxaloacetate, due to its rapid consumption by citrate synthase, drive the reaction forward according to $$\Delta G = \Delta G$$^{\circ\prime}$$ + RT \ln Q.$$

Question 2

A patient has a mutation that inactivates the mitochondrial malate–aspartate shuttle. Which of the following is the most direct metabolic consequence?

Accepted Answer

Cytosolic NADH cannot be oxidized in the mitochondria, reducing ATP production from glycolysis.

Question 3

Which enzyme catalyzes the reaction: $$	ext{Pyruvate} + 	ext{CoA} + 	ext{NAD}^+ ightarrow 	ext{Acetyl-CoA} + 	ext{CO}_2 + 	ext{NADH}$$, and what is a key cofactor it shares with $$\alpha-$$ketoglutarate dehydrogenase?

Accepted Answer

Pyruvate dehydrogenase; thiamine pyrophosphate (TPP)

Question 4

During one turn of the TCA cycle, which of the following is produced per acetyl-CoA molecule entering the cycle?

Accepted Answer

2 CO$$_2$$, 3 NADH, 1 QH$$_2$$, and 1 GTP (or ATP)

Question 5

Which statement best explains why oxygen consumption can increase while ATP yield falls in mitochondria?

Accepted Answer

Proton leak or uncoupling proteins allow protons to return to the matrix without driving ATP synthase, so electron transport (and O$$_2$$ use) continues but ATP synthesis is reduced.

Question 6

Which TCA cycle intermediate is directly exported to the cytosol to provide acetyl-CoA for lipid synthesis?

Accepted Answer

Citrate

Question 7

Which of the following best describes the role of NADPH generated by IDH1 and IDH2 isoforms?

Accepted Answer

It provides reducing power for biosynthetic reactions and antioxidant defense.

Question 8

Which electron transport chain complex does NOT pump protons across the mitochondrial inner membrane?

Accepted Answer

Complex II (succinate dehydrogenase)

Question 9

A cell is rapidly synthesizing fatty acids. Which metabolic adaptation is most likely to occur to support this process?

Accepted Answer

Increased export of citrate from the mitochondria to the cytosol

Question 10

Which of the following best explains why the malate–aspartate shuttle does not transport NADH itself across the mitochondrial inner membrane?

Accepted Answer

The inner mitochondrial membrane is impermeable to NADH, so reducing equivalents are transferred via malate.

Question 11

Which regulatory signal would most likely increase the flux through the TCA cycle in muscle during exercise?

Accepted Answer

Increased ADP concentration, which activates NAD$$^+-$$dependent isocitrate dehydrogenase (IDH3)

Question 12

Which of the following is an example of an anaplerotic reaction in the TCA cycle?

Accepted Answer

$$	ext{Pyruvate} + 	ext{HCO}_3^- + 	ext{ATP} ightarrow 	ext{Oxaloacetate} + 	ext{ADP} + 	ext{Pi} ($$catalyzed by pyruvate carboxylase)

Question 13

Which of the following best describes the fate of the two carbons from acetyl-CoA during the first turn of the TCA cycle?

Accepted Answer

They are not released as CO$$_2$$ during the first turn; the CO$$_2$$ released comes from oxaloacetate-derived carbons.

Question 14

Which of the following is a shared cofactor for both pyruvate dehydrogenase and $$\alpha-$$ketoglutarate dehydrogenase complexes?

Accepted Answer

Thiamine pyrophosphate (TPP)

Question 15

Which of the following best explains the role of NADH produced in the TCA cycle?

Accepted Answer

It donates electrons to the electron transport chain, driving proton pumping and ATP synthesis.

Question 16

Which of the following best describes the metabolic role of glutamine in the TCA cycle?

Accepted Answer

It is converted to glutamate and then to $$\alpha-$$ketoglutarate, providing anaplerotic input to the TCA cycle.

Question 17

Which of the following statements about reactive oxygen species (ROS) in mitochondria is correct?

Accepted Answer

Superoxide ($$	ext{O}_2$$^{\bullet-}$$) can form by one-electron reduction of O_2$ and is converted to H_2$O_2$ by superoxide dismutase (SOD).

Question 18

Which of the following best explains why high NADH levels inhibit the TCA cycle under conditions of abundant energy?

Accepted Answer

High NADH signals sufficient reducing equivalents, inhibiting dehydrogenases and slowing oxidative flux.

Question 19

Which of the following best describes the difference between acetyl-CoA entry into the TCA cycle and anaplerosis?

Accepted Answer

Acetyl-CoA entry provides two carbons for oxidation, while anaplerosis replenishes TCA intermediates withdrawn for biosynthesis.

Mitochondrial Metabolism: TCA Cycle, Electron Transport, and Metabolic Connections

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