Malate–aspartate shuttle

The shuttle system is required because the mitochondrial inner membrane is impermeable to NADH, the primary reducing equivalent of the electron transport chain.

The two malate dehydrogenases are differentiated by their location and structure, and catalyze their reactions in opposite directions in this process.

In this process, two electrons generated from NADH, and an accompanying H+, are attached to oxaloacetate to form malate.

Compare this to the glycerol 3-phosphate shuttle, which reduces FAD+ to produce FADH2, donates electrons to the quinone pool in the electron transport chain, and is capable of generating only 2 ATPs per NADH generated in glycolysis (ultimately resulting in a net gain of 36 ATPs per glucose metabolized).

(These ATP numbers are prechemiosmotic, and should be reduced in light of the work of Mitchell and many others[citation needed].