Malate-aspartate shuttle

The malate-aspartate shuttle (sometimes also the malate shuttle) is a biochemical system for translocating electrons produced during glycolysis across the semipermeable inner membrane of the for oxidative phosphorylation in eukaryotes. These electrons enter the electron transport chain of the mitochondria via reduction equivalents to generate ATP. The shuttle system is required because the mitochondrial inner membrane is impermeable to NADH, the primary reducing equivalent of the electron transport chain. To circumvent this, malate carries the reducing equivalents across the membrane.

The shuttle consists of four protein parts:

The primary enzyme in the malate-aspartate shuttle is malate dehydrogenase. Malate dehydrogenase is present in two forms in the shuttle system: mitochondrial malate dehydrogenase and cytosolic malate dehydrogenase. The two malate dehydrogenases are differentiated by their location and structure, and catalyze their reactions in opposite directions in this process.

First, in the cytosol, malate dehydrogenase catalyses the reaction of oxaloacetate and NADH to produce malate and NAD⁺. In this process, two electrons generated from NADH, and an accompanying H⁺, are attached to oxaloacetate to form malate.

Once malate is formed, the first antiporter (malate-alpha-ketoglutarate) imports the malate from the cytosol into the mitochondrial matrix and also exports alpha-ketoglutarate from the matrix into the cytosol simultaneously. After malate reaches the mitochondrial matrix, it is converted by mitochondrial malate dehydrogenase into oxaloacetate, during which NAD⁺ is reduced with two electrons to form NADH and an H⁺ is released. Oxaloacetate is then transformed into aspartate (since oxaloacetate cannot be transported into the cytosol) by mitochondrial aspartate aminotransferase. Since aspartate is an amino acid, an amino radical needs to be added to the oxaloacetate. This is supplied by glutamate, which in the process is transformed into alpha-ketoglutarate by the same enzyme.

...
Wikipedia