Fundamentals of Molecular Biology. Part 1: Molecular Biology of the Cell - A. N. Oguirtsov 2011

Oxidation of glucose and fatty acids
Electron transfer from the cytosol to the mitochondrion

To maintain continuous aerobic oxidation, the NADH produced in the process must be oxidized back to NAD⊕ in the Cytosol.

Much like the NADH generated within the mitochondrial matrix, electrons from cytosolic NADH are ultimately transferred to O2 via the Electron Transport Chain, thereby generating a proton-motive force.

Although The inner mitochondrial membrane is impermeable to NADH, it contains specialized transport Proteins known as electron shuttles, which transfer electrons from cytosolic NADH into the mitochondrial matrix.

The Mechanism of the most common shuttle, the malate-aspartate shuttle, is illustrated in Figure 158.

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Figure 158 - Diagram of the malate-aspartate shuttle

The malate-aspartate shuttle involves two antiporters located in the inner mitochondrial membrane—the malate/α-ketoglutarate antiporter and the glutamate/aspartate antiporter—along with two Enzymes, a transaminase and a malate dehydrogenase, present in both The Cell cytosol and the mitochondrial matrix.

Six consecutive steps make up the working cycle of the shuttle.

(1) Cytosolic malate dehydrogenase transfers an electron from cytosolic NADH to oxaloacetate, yielding malate.

(2) The antiporter simultaneously transports malate into the matrix while exporting α-ketoglutarate (2-oxoglutarate) out of the mitochondrial matrix.

(3) Mitochondrial malate dehydrogenase transfers an electron from malate (converting it back into oxaloacetate) to NAD⊕, reducing it to NADH.

(4) Oxaloacetate, which cannot cross the membrane, is converted into aspartate by acquiring an amino group via the mitochondrial enzyme transaminase (aspartate transaminase), which receives this amino group from glutamate. In the process, glutamate is converted into α-ketoglutarate (via a bisubstrate "ping-pong" reaction).

(5) A second antiporter exports aspartate into the cytosol in exchange for glutamate.

(6) The cycle is completed by cytosolic transaminase, which converts aspartate back into oxaloacetate through a bisubstrate "ping-pong" reaction (utilizing α-ketoglutarate / 2-oxoglutarate as the second substrate, which accepts the amino group from aspartate and is thereby converted into glutamate).

As a result of this electron shuttle, cytosolic NADH is oxidized to NAD⊕, while mitochondrial NAD⊕ is reduced to NADH:



Last update: 12/08/2026

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