Question

Explain what you understand from:

a) The glycerophosphate shuttle
b) The malate aspartate shuttle

In which tissues does each shuttle occur?

Answer 1

The reducing equivalent NADH generated during glycolysis cannot cross the inner mitochondrial membrane. The electrons from NADH are transferred to the electron transport chain for ATP generation. Therefore there exist two shuttle systems : Malate aspartate shuttle and glycerophosphate shuttle which help in transfer of electrons from NADH to electron transport chain.

In glycerophosphate shuttle, a cytosolic glycerol-3-phosphate dehydrogenase uses electrons from NADH to reduce dihydroxyacetone phosphate to glycerol-3-phosphate. Glycerol-3-phosphate is then oxidized by inner mitochondrial membrane bound glycerol- 3-phosphate dehydrogenase, electrons are transferred to enzyme bound FAD to form FADH₂. FADH₂ then transfers electrons to ubiquinones to enter the electron transport chain. This shuttle is present in brown adipose tissue to generate heat as the conversion is not very efficient.

Malate aspartate shuttle is the main type of shuttle used for transfer of NADH electrons from cytosol to mitochondria. Cytoplasmic malate dehydrogenase reduce oxalaoacetate to malate by oxidizing NADH to NAD⁺. malate then enter matrix via antiporter which moves malate into the matrix and exports alpha-ketogluatarate into the cytosol . Mitochondrial malate dehydrogenase carry out the reverse reaction of oxidizing malate to oxaloacetate and regenerating NADH. Oxaloacetate(cannot move across mitochondrial membrane) generated is converted to aspartate by mitochondrial aspartate amino transferase. The amino group required for aspartate formation is donated by glutamate. Glutamate is deaminated to alpha-ketogluatarate by the same enzyme. Glutamate-aspartate antiporter then exports aspartate( matrix to cytosol) and imports glutamate( cytosol to matrix). In cytosol aspartate is converted back to oxaloacetate by the same enzyme aspartate aminotransferase.

The net effect is the movement of NADH from cytosol to mitochondrial matrix.

Malate- aspartate shuttle occurs in liver, heart and kidney tissues.