Week 12

Question 1

What are the major regulatory enzymes of the TCA cycle?

Answer 1

• Citrate synthase
• Isocitrate dehydrogenase (rate-limiting)
• α-Ketoglutarate dehydrogenase complex

Question 2

How does substrate supply regulate the TCA cycle?

Answer 2

• Availability of acetyl-CoA and oxaloacetate (OAA) determines cycle rate
• Low OAA → acetyl-CoA accumulates → TCA slows
• Increased NAD⁺ and ADP stimulate cycle flux

Question 3

How does the NAD⁺/NADH ratio regulate the TCA cycle?

Answer 3

• High NADH inhibits dehydrogenases
• High NAD⁺ stimulates oxidative steps
• ETC activity indirectly regulates TCA by reoxidizing NADH

Question 4

Key allosteric activators of the TCA cycle?

Answer 4

• ADP
• Ca²⁺ (especially in muscle during contraction)

Question 5

Key allosteric inhibitors of the TCA cycle?

Answer 5

• ATP
• NADH
• Citrate
• Succinyl-CoA

Question 6

How is the TCA cycle regulated by covalent modification?

Answer 6

• Indirectly via pyruvate dehydrogenase (PDH)
• PDH is inhibited by phosphorylation (PDH kinase)
• PDH is activated by dephosphorylation (PDH phosphatase)

Question 7

Role of protein synthesis in TCA regulation?

Answer 7

• Long-term regulation via synthesis or degradation of enzymes
• Hormones (thyroxine, cortisol) increase mitochondrial enzyme expression

Question 8

What is produced in one turn of the TCA cycle?

Answer 8

• 3 NADH
• 1 FADH₂
• 1 GTP
• 2 CO₂

Question 9

ATP yield from one turn of the TCA cycle?

Answer 9

• NADH: 3 × 2.5 = 7.5 ATP
• FADH₂: 1 × 1.5 = 1.5 ATP
• GTP: 1 ATP
  Total = 10 ATP

Question 10

Total ATP yield from TCA cycle per glucose molecule?

Answer 10

• 2 acetyl-CoA → 2 cycles
• 20 ATP from TCA cycle alone

Question 11

What are anaplerotic reactions?

Answer 11

Reactions that replenish TCA cycle intermediates removed for biosynthesis

Question 12

Most important anaplerotic reaction?

Answer 12

• Pyruvate → Oxaloacetate
• Enzyme: Pyruvate carboxylase
• Requires biotin and ATP

Question 13

Other anaplerotic sources of TCA intermediates?

Answer 13

• Amino acids → α-ketoglutarate, succinyl-CoA, fumarate
• Propionyl-CoA → Succinyl-CoA

Question 14

Metabolic significance of anaplerotic reactions?

Answer 14

• Maintain TCA cycle flux
• Support ATP production
• Enable biosynthesis of glucose, fatty acids, amino acids

Question 15

What happens if the TCA cycle is disrupted?

Answer 15

• ↓ ATP production
• ↑ NADH → inhibits glycolysis and PDH
• Accumulation of lactate → lactic acidosis

Question 16

Why is the brain severely affected by TCA cycle defects?

Answer 16

• Brain depends heavily on aerobic glucose oxidation
• Cannot use fatty acids efficiently
• Energy failure → neurodegeneration

Question 17

Effect of PDH deficiency on the TCA cycle?

Answer 17

• Pyruvate cannot enter TCA
• ↑ Lactate → metabolic acidosis
• ↓ Acetyl-CoA → ↓ ATP

Question 18

How does arsenic poisoning affect the TCA cycle?

Answer 18

• Inhibits lipoic acid–dependent enzymes
• Blocks PDH and α-ketoglutarate dehydrogenase
• Leads to neurologic dysfunction and death

Question 19

Why is the TCA cycle called amphibolic?

Answer 19

• Participates in both catabolic (energy production)
• And anabolic (biosynthesis) pathways