Kreb’s or Citric acid cycle

The tricarboxylic acid cycle is also known as Kreb’s or Citric acid cycle. It is the main source of energy for cells and is also the part of aerobic respiration. The cycle converts the available chemical energy of acetyl coenzyme A (acetyl CoA) into NADH.

The TCA cycle is part of the larger glucose metabolism whereby glucose is oxidized to form pyruvate, which is then oxidized and enters the TCA cycle as acetyl-CoA.

Location:- Mitochondrial matrix

Generation of acetyl-CoA: Pyruvate is converted into acetyl CoA in the presence of oxygen. This reaction is catalyzed by pyruvate dehydrogenase enzyme complex, and generates CO2 and NADPH+H.  This step is also known as link reaction or transition step; because it links TCA and glycolysis. As two pyruvate molecules are formed from glycolysis so two molecules of acetyl-CoA and also 2 NADH are formed.

Pathway for TCA cycle

Regulation of TCA cycle

The TCA cycle is majorly regulated by the concentration of ATP and NADH. High ratios of ATP, acetyl-CoA and NADH will inhibit the cycle. Because excess of ATP and NADH occurs when energy supply is sufficient. It is also regulated in other two ways:

• Enzymatic regulation
  • Pyruvate dehydrogenase– this enzyme is inhibited by ATP, NADH and acetyl-CoA. This enzyme is stimulated by ADP and pyruvate.
  • Isocitrate dehydrogenase– It is stimulated by ADP and inhibited by ATP and NADH
  • Alpha-ketoglutarate– It is inhibited by succinyl-CoA, ATP and NADH.
• Hormonal regulation
  • insulin activates TCA cycle
  • glucagon inactivates TCA cycle

Bio-energetics of TCA cycle

Utilization and generation of ATP during Kreb’s cycle:

• 3 molecules of NADH:- 3*3= 9 ATP
• 1 molecule of FADH2:- 1*2=2 ATP
• 1 molecule of GTP:- 1*1=1 ATP

So total of 12 ATP molecules

Since, 1 glucose molecule gives two pyruvate molecules. and acetyl-CoA is generated from pyruvate, so overall ATP gain is 12*2 = 24 ATPs.

Significance of TCA cycle

1. It provides energy in the form of ATP molecules
2. TCA cycle provides substrate for respiratory chain
3. It is a amphibolic pathway, that is it plays important role in both anabolic as well as catabolic processes.
4. It also helps in energy expenditure.

Multiple choice questions (MCQs)

1. TCA cycle is also known as?
A. Citric acid cycle

B. Kreb’s cycle

C. Both

D. None

2. Which is the first compound formed in the TCA cycle?
A. Oxaloacetate

B. Citrate

C. Isocitrate

D. None of the above

3. The TCA cycle occurs in?
A. Mitochondrial matrix

B. Cytosol

C. Nucleus

D. Ribosomes

4. Which compound generates acetyl-CoA?
A. Lactate

B. Pyruvate

C. Glucose

D. Fructose

5. Match the following enzymes and its product-
a. Succinyl thiokinase 1. citrate
b. Succinyl dehydrogenase 2. isocitrate
c. Aconitase 3. fumerase
d. Citrate synthase 4. succinate

6. Which enzyme catalyzes the conversion of isocitrate to alpha-ketoglutarate?
A. Isocitrate dehydrogenase

B. Isocitrate carboxylase

C. Alpha-ketoglutarate dehydrogenase

D. Aldolase

7. Which hormone stimulates TCA cycle?
A. Glucagon

B. Insulin

C. Growth hormone

D. All of the above

8. Which hormone inhibits TCA cycle?
A. Glucagon

B. Insulin

C. Growth hormone

D. All of the above

9. Which compound is considered to play the catalytic role in TCA cycle?

A. Citrate

B. Isocitrate

C. Oxaloacetate

D. Alpha-ketoglutarate

10. The TCA is the final common oxidative pathway for which bio-molecule?

A. Carbohydrates

B. Fats

C. Amino acids

D. All of the above

11. TCA cycle generates how many ATP molecules?
A. 10 ATP

B. 12 ATP

C. 20 ATP

D. 24 ATP

12. Which of the following enzyme requires FAD as energy molecule?
A. Citrate synthase

B. Succinate thiokinase

C. Fumerase

D. None of the above

13. Which of the following statement is NOT true?
A. It occurs in mitochondria matrix of the cell
B. It also helps in fructose metabolism
C. TCA cycle generates ATP
D. TCA cycle generates CO2

14. There is no direct participation of oxygen in the Kreb’s cycle, but the cycle operates only in aerobic conditions. Why?

A. Oxaloacetate is generated only in presence of oxygen

B. FAD is generated only in presence of oxygen

C. NAD+ is generated Only in presence of oxygen

D. Both B and C

15. Which of the following vitamin is necessary for the TCA cycle?

A. Thiamine

B. Biotin

C. Vitamin E

D. All of the above

ANSWERS:-

1. Both

2. Citrate

3. Mitochondrial matrix

4. Pyruvate

5. a – 4 b – 3 c – 2 d – 1

6. Iso-citrate dehydrogenase

7. Insulin

8. Glucagon

9. Oxaloacetate

10. All of the above

11. 24 ATP

12. None of the above

13. TCA cycle generates CO2

14. Both B and C

15. Thiamine

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REFERENCE:- 1. Pankaja Naik- Biochemistry; 4^th edition; page no:- 172-176.

2. U Satyanarayana, U Chakrapani-Biochemistry; 4th edition; Page no:- 254-257