Shuttle System for Oxidation of Extra Mitochondrial NADH and MCQs with answer for GPAT, NEET PG, NET , GATE

Shuttle System for Oxidation of Extra Mitochondrial NADH and MCQs with answer for GPAT, NEET PG, NET , GATE

Most of the NADH and FADH2 which enters the mitochondrial ETC, arises from the kreb’s cycle or beta-oxidation of fatty acids. Now since the inner mitochondrial membrane is impermeable to the cytoplasmic NADH, so that’ why the NADH generated through the glycolysis must have a special route to enter the mitochondria. Special shuttle systems carry the reducing equivalents and cytosolic NAH into the mitochondria by an indirect route. Two such shuttle systems are:

  • Malate-aspartate shuttle system
  • Glycerol-phosphate shuttle system

Malate-Aspartate shuttle system

This is the most active NADH shuttle which works in liver, kidney and heart mitochondria. This system is mediated by two membrane carriers and four enzymes. Steps involved in this process are:

  • Firstly the reducing equivalents of cytosolic NADH are converted to cytosolic oxaloacetate to form malate. This reaction is catalyzed by cytosolic malate dehydrogenase (cytosolic MDH)
  • Now malate which carries the reducing equivalents is transported across the inner membrane by malate-alpha-ketoglutarate transport system
  • These reducing equivalents are then transferred to the mitochondrial NAD+ by mitochondrial malate dehydrogenase (mitochondria MDH) and the malate itself gets oxidized into oxaloacetate.
  • The resulting mitochondrial NADH is oxidized and yields 2.5 molecules of ATP per electron pair.
  • Since the oxaloacetate cannot pass through the membrane from mitochondria to the cytosol back so that’s why it is converted to aspartate.
  • Aspartate is then transferred to the cytosolic side by the amino acid transport system
  • In the cytosol, a reverse reaction takes place and it converts aspartate back into oxaloacetate and glutamate
  • In this way, malate-aspartate system completes.

Glycerol-phosphate shuttle

This shuttle is also known as glycerol-3-phosphate shuttle. This shuttle works in skeletal muscle and brain mitochondria. The difference between the two shuttle is the number of ATP molecules formed per electron pair. That is the malate aspartate shuttle yields 2.5 molecules of ATP per electron pair whereas glycerol-phosphate system yields 1.5 molecules of ATP per electron pair. The steps involved in this process are:

  • Firstly, a pair of electrons from the cytosolic NADH is transferred to dihydroxy-acetone phosphate (DHAP) to form glycerol-3-phosphate by cytosolic glycerol-3-phosphate dehydrogenase enzyme.
  • The formed glycerol-3-phosphate than diffuses from the outer mitochondrial membrane to the inter-membrane space of the mitochondria
  • Now the glycerol-3-phosphate is re-oxidized to dihydroxy-acetone phosphate on the outer surface of the inner mitochondrial membrane
  • The electron pair from the glycerol-3-phosphate is transferred to FAD of the enzyme to form FADH2. Since the mitochondrial enzyme is linked to the respiratory chain via FAD and not NAD so it yields 1.5 molecules of ATP per electron pair.
  • The DHAP returns back to the cytosol. It can again be reused for the reduction of glycerol-3-phosphate.

Multiple Choice Questions MCQs

1. Why is the Shuttle system necessary?

A. For the transfer of cytosolic NADH

B. For the transfer of oxidizing equivalents

C. To carry out redox reaction

D. Both B and C

2. Which of the following is carried by the shuttle system?

A. Cytosolic NADH

B. Reducing equivalents

C. Oxidizing equivalents

D. Both A AND b

3. How many shuttle systems are present in the body?

A. 2

B. 3

C. 4

D. 6

4. In which organ, malate-aspartate shuttle system works?

A. Kidney

B. Liver

c. Heart

D. All of the above

5. In which organ, glycerol-phosphate shuttle system works?

A. Brain

B. Stomach

C. Eyes

D. Kidney

6. What is the reason that the malate aspartate shuttle system yields 2.5 molecules of ATP per electron pair?

A. Mitochondrial enzyme is linked to the respiratory chain via FAD

B. Mitochondrial enzyme is linked to the respiratory chain via NAD

C. Mitochondrial enzyme is linked to the respiratory chain via complex-3

D. None of the above

7. How many enzymes mediate the malate-aspartate shuttle system?

A. 2

B. 3

C. 4

D. 5

8. Match the following enzyme and the product it forms-

a. Mitochondrial MDH    1. Glycerol-3-phosphate

b. Cytosolic MDH              2. DHAP

c Mitochondrial glycerol-3-phosphate dehydrogenase        3. oxaloacetate

d. Cytosolic glycerol-3-phosphate dehydrogenase                 4. malate

9. Which system transports the malate across the inner mitochondrial membrane?

A. Amino acid transport

B. Malate-ketoglutarate system

C. Sodium dependent channels

D. All of the above

10. What is the product formed due to the transfer of electron pair from cytosolic NADH to dihydroxy-acetone?

A. Oxaloacetate

B. Aspartate

C. Glycerol-3-phosphate

D. Malate

11. What is the reason that the glycerol-phosphate shuttle system yields 1.5 molecules of ATP per electron pair?

A. Mitochondrial enzyme is linked to the respiratory chain via FAD

B. Mitochondrial enzyme is linked to the respiratory chain via NADH

C. Mitochondrial enzyme is linked to the respiratory chain via complex-3

D. None of the above

12. Which of the following statement is NOT true?

A. Most of the NADH entering the ETC arises from TCA cycle

B. Malate-aspartate shuttle is mediated by 2 membrane carriers

C. In cytosol, aspartate reverses back to oxaloacetate and lactate

D. Glycerol-3-phospate through the outer mitochondrial membrane into intermembrane space

13. Which out of the following is termed as the active NADH shuttle?

A. Malate-aspartate shuttle

B. Glycerol-phosphate shuttle

C Sodium dependent shuttle

D. None of the above

14. The oxaloacetate is converted to which compound so that it can cross the mitochondrial membrane?

A. Oxaloacetate

B. Malate

C. Glycerol-3-phosphate

D. None of the above

15. Which enzyme catalyzes the transfer of cytosolic NADH to cytosolic oxaloacetate to form malate?

A. Cytosolic malate dehydrogenase

B. Oxidoreductase

C. Mitochondrial malate dehydrogenase

D. Both A and C

ANSWERS:-

1. For the transfer of cytosolic NADH

2. Both A and B

3. 2

4. All of the above

5. Brain

6. Mitochondrial enzyme is linked to the respiratory chain via NAD

7. 4

8. a – 3 b – 4 c – 2 d – 1

9. Malate-ketoglutarate system

10. Glycerol-3-phosphate

11. Mitochondrial enzyme is linked to the respiratory chain via FAD

12. In cytosol, aspartate reverses back to oxaloacetate and lactate

13. Malate-aspartate system

14. None of the above

15. Cytosolic malate dehydrogenase

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REFERENCE:- Pankaja Naik- Biochemistry; 4th edition; page no:- 153-155

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