Malate-Aspartate Shuttle

1. 1

   Cytosolic oxaloacetate + NADH + H+ -> malate + NAD+

   Cytosolic malate dehydrogenase (MDH1) 1.1.1.37 ST-0353 Reversible NADH
   In Cytosolic oxaloacetate NADH H+

   Out Malate NAD+
   › Notes

   Captures cytosolic (glycolytic) reducing equivalents as malate.

2. 2

   Malate(cytosol) + alpha-ketoglutarate(matrix) <-> malate(matrix) + alpha-ketoglutarate(cytosol)

   Malate-alpha-ketoglutarate antiporter (SLC25A11) ST-0354 Reversible
   In Malate(cytosol) alpha-ketoglutarate(matrix) <

   Out Malate(matrix) Alpha-ketoglutarate
   › Notes

   Transport step, not enzymatic.

3. 3

   Malate + NAD+ -> oxaloacetate + NADH + H+ (matrix)

   Mitochondrial malate dehydrogenase (MDH2) 1.1.1.37 ST-0355 Reversible NAD+
   In Malate NAD+

   Out Oxaloacetate NADH H+
   › Notes

   Regenerates matrix NADH, which enters at Complex I - hence ~2.5 ATP per cytosolic NADH.

4. 4

   Oxaloacetate + glutamate <-> aspartate + alpha-ketoglutarate (matrix)

   Mitochondrial aspartate aminotransferase (GOT2) ST-0356 Reversible PLP (B6)
   In Oxaloacetate Glutamate <

   Out Aspartate Alpha-ketoglutarate
   › Notes

   Oxaloacetate cannot cross the membrane, so it leaves as aspartate.

5. 5

   Aspartate(matrix) + glutamate(cytosol) -> aspartate(cytosol) + glutamate(matrix)

   Glutamate-aspartate antiporter (citrin/aralar, SLC25A13/12) ST-0357 Irreversible/directional
   In Aspartate(matrix) Glutamate

   Out Aspartate(cytosol) Glutamate
   › Notes

   Completes the cycle; cytosolic AST (GOT1) then reforms oxaloacetate. Dominant shuttle in liver, kidney and heart.

Showing all 5 steps.