Malate Aspartate Shuttle

• The process of synthesizing ATP from ADP & Pi coupled with electron transport chain is known as oxidative phosphorylation.
• For this oxidation to take place, many components are required. One of them is NADH, the reducing equivalent.

Transport of reducing Equivalents – the shuttle pathways.

• The inner mitochondrial membrane is impermeable to most charged particles. It lacks NADH transporter.
• Therefore, NADH produced in the cytosol cannot directly enter the mitochondria.
• However, two electrons of NADH are transported from cytosol into the matrix of mitochondria using shuttle pathways.

1. Malate Aspartate Shuttle
2. Glycerol Phosphate Shuttle.

Malate Aspartate Shuttle

1. In the cytosol, oxaloacetate accepts reducing equivalents (NADH) and becomes malate.
2. Malate then enters mitochondria & gets oxidised by mitochondrial malate dehydrogenase . In this reaction, NADH & oxaloacetate are regenerated.
3. NADH that enters the matrix gets oxidised via the electron transport chain & 3 ATP are produced.
4. Now the oxaloacetate generated participates in transamination reaction with glutamate to produce aspartate &alpha- ketoglutarate.
5. The aspartate & alpha – ketoglutarate then undergo transamination to give oxaloacetate & glutamate and the cycle continues.
6. Thus, 3 ATP per mole of NADH is generated by Malate Aspartate shuttle.

• Another pathway, the Glycerol Phosphate Shuttle works to transport the reducing equivalent, FAD.

But, in this pathway, only 2 ATP molecules are generated.

• Liver & Heart utilize the malate- aspartate shuttle to produce ATP.

   While other tissues use the Glycerol Phosphate Shuttle

• Regulation

The activity of malate-aspartate shuttle is modulated by arginine methylation of Malate dehydrogenase 1 (MDH1). Protein arginine N-methyltransferase CARM1 methylates and inhibits MDH1 by disrupting its dimerization, which represses malate-aspartate shuttle and inhibits mitochondrial respiration of pancreatic cancer cells.

Contributed by: Soumya Khot