Week 4: TCA Cycle

Question 1

TCA AKA

Answer 1

Tricarboxylic acid Cycle (modeled after 3 C citrate)

Question 2

TCA Cycle Step 1 reaction

Answer 2

Pyruvate + NAD+ +CoASH -pyruvate dehydrogenase-> Acetyl-CoA + NADH + CO2

Question 3

TCA Cycle Step 2 reaction

Answer 3

Acetyl CoA + Oxaloacetate -Citrate Synthase-> Citrate + H2O

*Irreversible* very exothermic reaction very high -ΔG

Question 4

Oxaloacetate # of Cs

Answer 4

4

Question 5

Acetyl CoA # of Cs

Answer 5

2Cs

Question 6

Citrate # of Cs

Answer 6

6 Cs

Question 7

TCA Cycle Step 3 Reaction

Answer 7

Citrate <-Aconitase-> Isocitrate

*Reversible* depends on substrate product relationship

Question 8

TCA Cycle Step 3 reversibility

Answer 8

Reversible

Question 9

TCA Cycle Step 4 Reaction

Answer 9

Isocitrate + NAD+ -Isocitrate Dehydrogenase-> α-ketoglutarate + NADH + CO2

Question 10

TCA Cycle Step 5 Reaction

Answer 10

α-Ketoglutarate + NAD+ -α-Ketoglutarate DH-> Succinyl-CoA + NADH + CO2

*Irreversible* very exothermic reaction very high -ΔG

Question 11

What happens to the CO2 that is being generated

Answer 11

CO2 diffuses into the blood and RBCs

CO2 + H2O <-Carbonic Anhydrase-> HCO3- + H+

Travels to Lungs

HCO3- + H+ <-Carbonic Anhydrase-> CO2 + H2O

CO2 is expired

Question 12

TCA Cycle Step 6 Reaction

Answer 12

Succinyl-CoA + GDP -Succinate Thiokinase-> Succinate + GTP + CoASH

Question 13

TCA Cycle Step 7 Reaction

Answer 13

Succinate + FAD+ -Succinate Dehydrogenase-> Fumarate + FADH2

FADH2 electrons are released at the level of Coenzyme Q in the ETC

Question 14

Describe the structure of Succinate Dehydrogenase

Answer 14

• FAD+ or FADH2 is coupled to the enzyme and does not dissociate
• Enzyme itself is embedded in the inner mitochondrial membrane facing the matrix

Question 15

TCA Cycle Step 8 Reaction

Answer 15

Fumarate + H2O -Fumarase-> Malate

Question 16

TCA Cycle Step 9 Reaction

Answer 16

Malate + NAD+ -Malate DH-> Oxaloacetate + NADH

ΔG= +7.1

You would think the reverse reaction would be more likely

However, in skeletal muscle, the [oxaloacetate] is very low so this drives the reaction forward to form oxaloacetate

*This feature is very important in the liver to produce glucose in the liver in gluconeogenesis* (ONLY IN THE LIVER)

Question 17

TCA Cycle Step 10 Reaction

Answer 17

Oxaloacetate enters the cycle again to form another citrate

Oxaloacetate + Acetyl-CoA -Citrate Synthase-> Citrate

Question 18

DH enzyme regulation in the TCA cycle

Answer 18

Regulated by NADH:NAD+

High [NADH] inhibits

High [NAD+] Activates