Reactions of the Citric Acid Cycle

Question 1

Where does the citric acid cycle take place

Answer 1

In the mitochondrial matrix

Question 2

Step 1- Citrate Formation

Answer 2

First, acetyl-coA and oxaloacetate undergo a condensation reaction to form citryl-CoA, an intermediate.
Then, the hydrolysis of citryl-CoA yields citrate and CoA-SH
Reaction catalyzed by citrate synthase

Question 3

Step 2- Citrate Isomerized to Isocitrate

Answer 3

Achiral citrate is isomerized to one of 4 possible isomers of isocitrate –> basically the switching of a hydrogen and hydroxyl group.

Question 4

Step 3- alpha-ketoglutarate and CO2 Formation

Answer 4

Isocitrate is first oxidized to oxalosuccinate by isocitrate dehydrogenase. Then oxalosuccinate is decarboxylated to produce alpha-ketoglutarate and CO2.
Isocitrate dehydrogenase is the rate-limiting enzyme of the citric acid cycle
1st of 2 carbons from cycle lost here
1st NADH produced from intermediates in cycle.

Question 5

Step 4- Succinyl-CoA and CO2 Formation

Answer 5

These reactions are carried out by the alpha-ketoglutarate dehydrogenase complex.
Alpha-ketoglutarate and CoA come together –> CO2 molecule and another NADH molecule produced.

Question 6

Step 5 - Succinate Formation

Answer 6

Hydrolysis of the thioester bond on succinyl-CoA yields succinate and CoA-SH, and is coupled to the phosphorylation of GDP to GTP.
Catalyzed by succinyl-CoA synthetase –> creates new covalent bonds WITH energy input

Question 7

Step 6 - Fumarate formation

Answer 7

Occurs on inner membrane instead of in matrix.
Succinate undergoes oxidation to yield fumarate –> reaction is catalyzed by succinate dehydrogenase: considered a flavoprotein because it is covalently bonded to FAD, the electron acceptor in this reaction.
As succinate is oxidized to fumarate, FAD is reduced to FADH2.

Question 8

Step 7 - Malate Formation

Answer 8

The enzyme fumarase catalyzes the hydrolysis of the alkene bond in fumarate, thereby giving rise to malate.

Question 9

Step 8 - Oxaloacetate formed anew

Answer 9

The enzyme malate dehydrogenase catalyzes the oxidation of malate to oxaloacetate. A third and final molecule of NAD+ is reduced to NADH.

Question 10

Substrates of Citric Acid Cycle

Answer 10

Please, Can I Keep Selling Seashells For Money, Officer?

• Pyruvate
• Citrate
• Isocitrate
• alpha-Ketoglutarate
• Succinyl-CoA
• Succinate
• Fumarate
• Malate
• Oxaloacetate

Question 11

Net Results and ATP yield

Answer 11

For 1 molecule of glucose:
From Glycolysis: 2 ATP and 2 NADH
From Pyruvate processing: 2 NADH
From citric acid cycle: 6 NADH, 2 FADH2, and 2 GTP

Total:
ATP: 2 + 2 = 4
10 NADH--> 25 ATP (2.5 ATP per NADH)
2 FADH2 --> 3 ATP (1.5 ATP per FADH2)
= 25 + 3 + 4 = 32 ATP

Question 12

3 Main control points of Citric Acid Cycle

Answer 12

Citrate synthase, Isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase complex

Question 13

Citrate Synthase is inhibited by what

Answer 13

ATP, NADH, succinyl-CoA, citrate

Question 14

Isocitrate dehydrogenase is inhibited by what

Answer 14

ATP, NADH

Question 15

alpha-ketoglutarate is inhibited by what

Answer 15

ATP, NADH, and succinyl-CoA