TCA Cycle

Question 1

1) Where does TCA cycle occur and what is its function?

Answer 1

• Mitochondrial matrix

- Energy trapping and biosynthesis of intermediates

Question 2

2) Describe the Link Reaction

Answer 2

CH3COOH + CoASH –> CH3CO-SCoA + CO2
- enzyme: pyruvate dehydrogenase
- cofactor: NAD+ –> NADH + H+
(CoA forms thioester bonds with carboxylic acids)

Question 3

3) Reaction#1: condensation reaction

Answer 3

Oxaloacetate –> Citrate

• enzyme: citrate synthase
• addition of Acetyl CoA

Question 4

4) Reaction#2: isomerisation reaction

Answer 4

Citrate –> Isocitrate

Question 5

5) Reaction#3: first CO2 loss

Answer 5

Isocitrate –> alpha-ketoglutarate/ 2-oxo glutarate

• enzyme: isocitrate dehydrogenase
• NAD+ –> NADH + H+
• CO2 produced

Question 6

6) Reaction#4: second CO2 loss

Answer 6

Alpha-ketoglutarate –> Succinyl CoA

• enzyme: alpha-ketoglutarate dehydrogenase
• addition of CoA-SH (coenzyme A)
• NAD –> NADH+ + H+
• CO2 produced

Question 7

7) Reaction#5: trapping thioester bond energy as GTP

Answer 7

Succinyl CoA –> Succinate

• loss of coenzyme A
• GDP + Pi –> GTP

Question 8

8) Reaction#6: conversion of succinate to fumarate

Answer 8

Succinate –> Fumarate
[succinate dehydrogenase]
- FAD –> FADH2

Question 9

9) Reaction #7: conversion of fumarate to malate

Answer 9

Fumarate –> Malate

-addition of H20

Question 10

10) Reaction #8: conversion of malate to oxaloacetate

Answer 10

Malate –> Oxaloacetate
[malate dehydrogenase]
- NAD+ –> NADH + H+

Question 11

11) Total energy yield of TCA cycle?

Answer 11

3 x NADH (2.5)
1 x FADH2 (1.5)
[NADH and FADH2 reduced cofactors are produced by dehydrogenase enzymes]

1 x GTP (1)
= 10 ATP

Question 12

12) What are the 3 irreversible (regulatory) reactions?

Answer 12

• Citrate synthase
• Isocitrate dehydrogenase (co2 produced)
• alpha-ketoglutarate dehydrogenase (co2 produced)

Question 13

13) What are inhibitors for citrate synthase?

Answer 13

• ATP, NADH, succinyl-CoA

Question 14

14) Inhibitors and activator of isocitrate dehydrogenase?

Answer 14

• ATP, NADH

- activated by ADP

Question 15

15) Inhibitors of alpa-ketoglutarate dehydrogenase?

Answer 15

• NADH, succinyl-CoA

Question 16

16) What can oxaloacetate, alpha-ketoglutarate and succinyl-coa be transaminated/ converted into? (production of biosynthetic precursors)

Answer 16

• oxaloacetate –> aspartate
• alpha-ketoglutarate –> glutamate
• succinyl-coa –> haem

Question 17

17) Which 2 reactions allow anaplerotic ‘topping up’ of the TCA cycle?

Answer 17

• pyruvate –> oxaloacetate (pyruvate carboxylase enzyme)
  (oxaloacetate converted to phosphoenol pyruvate by PEP carboxylase enzyme, which forms glucose)
• pyruvate –> malate (via malic enzyme)