Transporters in the Inner Mitochondrial Membrane Allow the Uptake of Electrons from Cytosolic NADH

For aerobic oxidation to continue, the NADH produced during glycolysis in the cytosol must be oxidized to NAD + . As with NADH generated in the mitochondrial matrix, electrons from cytosolic NADH are ultimately transferred to O2 via the respiratory chain, concomitant with the generation of

▲ FIGURE 8-10 The malate shuttle. This cyclical series of reactions transfers electrons from NADH in the cytosol (intermembrane space) across the inner mitochondrial membrane, which is impermeable to NADH itself. Step 11: Cytosolic malate dehydrogenase transfers electrons from cytosolic NADH to oxaloacetate, forming malate. Step 12 : An antiporter (blue oval) in the inner mitochondrial membrane transports malate into the matrix in exchange for a-ketoglutarate. Step |3| : Mitochondrial malate dehydrogenase converts malate back to oxaloacetate, reducing NAD+ in the matrix to NADH in the process. Step |4| : Oxaloacetate, which cannot directly cross the inner membrane, is converted to a proton-motive force. Although the inner mitochondrial membrane is impermeable to NADH itself, several electron shuttles can transfer electrons from cytosolic NADH to the matrix.

Operation of the most widespread shuttle—the malate-aspartate shuttle—is depicted in Figure 8-10. Critical to the shuttle are two antiport proteins in the inner mitochondrial membrane, a malate/a-ketoglutarate antiporter and a glutamate/aspartate antiporter, that permit transport of their aspartate by addition of an amino group from glutamate. In this transaminase-catalyzed reaction in the matrix, glutamate is converted to a-ketoglutarate. Step 15: A second antiporter (red oval) exports aspartate to the cytosol in exchange for glutamate. Step 16: A cytosolic transaminase converts aspartate to oxaloacetate, completing the cycle. The blue and red arrows reflect the movement of the a-ketoglutarate and glutamate, respectively. In step 14 glutamate is deaminated to a-ketoglutarate, which is transported to the cytosol by an antiporter (step |2|; in step |6|, the a-ketoglutarate is aminated, converting it back to glutamate, which is transported to the matrix by the antiporter in step |5|.

Cytosol

NADHcytosol NAD

cytosol

Cytosol

NADHcytosol NAD

cytosol

Matrix

NADHmatrix NAD'matrix

Matrix

NADHmatrix NAD'matrix substrates into and out of the matrix. Because oxaloacetate, one component of the shuttle, cannot directly cross the inner membrane, it is converted to the amino acid aspartate in the matrix and to malate in the cytosol. The net effect of the reactions constituting the malate-aspartate shuttle is oxidation of cytosolic NADH to NAD+ and reduction of matrix NAD+ to NADH:

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