Week 11

Question 1

What reaction links glycolysis to the TCA cycle?

Answer 1

Pyruvate → Acetyl-CoA (oxidative decarboxylation)

Question 2

What enzyme complex catalyzes this reaction?

Answer 2

Pyruvate dehydrogenase (PDH) complex

Question 3

Enzymes of PDH complex?

Answer 3

E1: PDH (decarboxylase) → E2: Dihydrolipoyl transacetylase → E3: Dihydrolipoyl dehydrogenase

Question 4

Cofactors required for PDH?

Answer 4

TPP (B1), lipoic acid, FAD (B2), NAD⁺ (B3), CoA (B5)

Question 5

Role of thiamine (B1)?

Answer 5

Forms TPP needed for oxidative decarboxylation of pyruvate and α-ketoglutarate

Question 6

What happens in PDH deficiency?

Answer 6

Pyruvate → lactate → lactic acidosis, ↓ ATP, neurologic damage

Question 7

Inheritance of PDH deficiency?

Answer 7

X-linked

Question 8

Symptoms of PDH deficiency?

Answer 8

Lactic acidosis, neurodegeneration, muscle spasticity, early death

Question 9

What is Wernicke-Korsakoff syndrome?

Answer 9

Encephalopathy due to thiamine deficiency

Question 10

Cause of Wernicke-Korsakoff?

Answer 10

Chronic alcoholism or malnutrition

Question 11

Why does thiamine deficiency affect brain?

Answer 11

Brain depends on TCA cycle for ATP

Question 12

What causes lactic acidosis in TCA defects?

Answer 12

Pyruvate cannot enter TCA → converted to lactate

Question 13

How does arsenic poison metabolism?

Answer 13

Binds lipoic acid and inhibits PDH and α-KG dehydrogenase

Question 14

Effect of arsenic poisoning?

Answer 14

Pyruvate accumulates → lactic acidosis → neurologic damage

Question 15

What is fluoroacetate?

Answer 15

Suicide substrate (rat poison)

Question 16

How does fluoroacetate kill cells?

Answer 16

Converted to fluorocitrate → inhibits aconitase

Question 17

Result of aconitase inhibition?

Answer 17

Citrate accumulates → TCA stops

Question 18

First enzyme of TCA cycle?

Answer 18

Citrate synthase

Question 19

Enzyme inhibited by fluorocitrate?

Answer 19

Aconitase

Question 20

First oxidative decarboxylation step?

Answer 20

Isocitrate → α-ketoglutarate

Question 21

Second oxidative decarboxylation step?

Answer 21

α-ketoglutarate → succinyl-CoA

Question 22

Which step produces GTP?

Answer 22

Succinyl-CoA synthetase

Question 23

Which step is part of ETC complex II?

Answer 23

Succinate dehydrogenase

Question 24

Products per turn of TCA (per acetyl-CoA)?

Answer 24

3 NADH, 1 FADH₂, 1 GTP, 2 CO₂

Question 25

ATP from 1 NADH?

Answer 25

~2.5 ATP

Question 26

ATP from 1 FADH₂?

Answer 26

~1.5 ATP

Question 27

Total ATP per TCA turn?

Answer 27

~10 ATP

Question 28

ATP from TCA per glucose?

Answer 28

~20 ATP

Question 29

Main regulatory enzymes?

Answer 29

Citrate synthase → Isocitrate dehydrogenase → α-ketoglutarate dehydrogenase

Question 30

Activators of isocitrate dehydrogenase?

Answer 30

ADP, Ca²⁺

Question 31

Inhibitors of isocitrate dehydrogenase?

Answer 31

ATP, NADH

Question 32

Inhibitors of α-ketoglutarate dehydrogenase?

Answer 32

NADH, succinyl-CoA

Question 33

How does NADH regulate the cycle?

Answer 33

High NADH inhibits TCA enzymes

Question 34

How does substrate supply regulate TCA?

Answer 34

Depends on availability of acetyl-CoA and oxaloacetate

Question 35

What are anaplerotic reactions?

Answer 35

Reactions that replenish TCA intermediates

Question 36

Major anaplerotic reaction?

Answer 36

Pyruvate → oxaloacetate (pyruvate carboxylase)

Question 37

Why are anaplerotic reactions important?

Answer 37

Maintain TCA function when intermediates are removed

Question 38

What are cataplerotic reactions?

Answer 38

Removal of TCA intermediates for biosynthesis

Question 39

Why is TCA cycle amphibolic?

Answer 39

It is both catabolic and anabolic

Question 40

TCA intermediate used for fatty acid synthesis?

Answer 40

Citrate

Question 41

TCA intermediate used for amino acid synthesis?

Answer 41

α-ketoglutarate and oxaloacetate

Question 42

Role of NAD⁺/NADH ratio in TCA?

Answer 42

High NAD⁺ stimulates TCA; high NADH inhibits it

Question 43

Effect of TCA cycle inhibition?

Answer 43

↓ ATP production

Question 44

Effect on pyruvate metabolism?

Answer 44

Pyruvate converted to lactate → lactic acidosis

Question 45

Organs most affected by TCA defects?

Answer 45

Brain and muscle