The Citric Acid Cycle (TCA)

Question 1

Outline the reactions of the TCA cycle

Answer 1

1. ) Acetyl-CoA –> Citrate Synthase Enzyme –> Citrate + releases CoA
2. ) Citrate –> Aconitase –> Isocitrate (Isomer of Citrate)
3. ) Isocitrate –> Isocitrate Dehydrogenase (inhibited by high ATP and NADH levels and stimulated by high ADP and Ca2+ levels, RATE LIMITING STEP) –> a-Ketogluterate (One NADH and one CO2 produced)
4. ) a-Ketogluterate –> a-Ketogluterate Dehydrogenase –> Succinyl-CoA (One NADH and one CO2 produced) [This step requires 5 Cofactors: Thiamine (vitamin B1), Lipoic Acid, Coenzyme A (vitamin B5), FAD+ (vitamin B2/riboflavin), NAD+ (vitamin B3/niacin)
5. ) Succinyl-CoA –> Succinate Thiokinase –> Succinate (Produces one GTP)
6. ) Succinate –> Succinate Dehydrogenase –> Fumarate (FADH2 produced)
7. ) Fumarate –> Fumarate Hydrase adds H2O –> Malate
8. ) Malate –> Malate Dehydrogenase –> Oxaloacetate (produces 1 NADH)
9. ) Oxaloacetate can be converted back to Citrate

Question 2

Citric Acid Cycle - Basics

Answer 2

• Main enzyme: Dehydrogenases
• 8 Enzymatic Reactions
• Starts with molecule Acetyl-CoA which ultimately gets converted to CO2

Question 3

Starvation State

Answer 3

• Increase in glucagon, epinephrine, and cortisol

- Fatty acids become main source of Acetyl-CoA

Question 4

Fed State

Answer 4

• Increase in insulin

- Plenty of Acetyl-CoA from breaking down glucose, fructose, and galactose

Question 5

Sources of Acetyl-CoA

Answer 5

• Fatty Acids (Starvation State)
• Glucose/Fructose/Galactose (Fed State)
• Alcohol in the liver
• Proteins

Question 6

What are the products of the TCA cycle?

Answer 6

One Acetyl-CoA produces 3 NADH, 1 FADH2, 1 GTP, and 2 CO2

Each NADH can make 3 ATPs (Thus 9 ATP per Acetyl-CoA)

Each FADH2 can make 2 ATPs

1 GTP has = energy of 1 ATP

12 ATP per AcetylCoA

Question 7

Which reactions of the TCA cycle are sensitive to deficiencies in vitamins and which clinical syndromes are associated with them?

Answer 7

Step 4.) a-Ketogluterate –> a-Ketogluterate Dehydrogenase –> Succinyl-CoA

Mnemonic: T-rex Loves and Cares For Nachos
This step requires 5 Cofactors: Thiamine (vitamin B1), Lipoic Acid, Coenzyme A (vitamin B5), FAD+ (vitamin B2/riboflavin), NAD+ (vitamin B3/niacin)

• Thiamine deficiency: Beriberi –> CNS and heart can’t work properly
• Niacin Deficiency –> Pellagra: Diarrhea, dermatitis, dementia, death

Question 8

What happens to Pyruvate in the Mitochondria? (Note this step links Glycolysis to TCA Cycle, but isn’t considered a part of either)

Answer 8

The Enzyme Pyruvate Dehydrogenase:

• Removes an electron from Pyruvate and gives it to NAD+ to form NADH
• Removes CO2
• Adds CoA-SH to Pyruvate making Acetyl-CoA

Question 9

Citric Acid Cycle - Basics

Answer 9

• Main enzyme: Dehydrogenases
• 8 Enzymatic Reactions
• Starts with molecule Acetyl-CoA which ultimately gets converted to CO2
• Hormones don’t play a role in regulating the TCA
• Occurs in the mitochondria matrix

Question 10

How many ATP does 1 glucose make in the TCA?

Answer 10

Since 1 glucose makes 2 Pyruvate in glycolysis which can be converted to 2 Acetyl-CoA, and each Acetyle-CoA make 12 ATP in TCA cycle, 1 glucose then makes 24 ATP in TCA cycle