Question

During gluconeogenesis, reducing equivalents from mitochondria to the cytosol are transported by:

• A. Malate.
• B. Aspartate.
• C. Glutamate.
• D. Oxaloacetate.

Hint:

Oxaloacetate is reduced to malate inside mitochondria, malate crosses the membrane, then gets oxidized back in the cytosol to release NADH.

Answer 1

The Correct Option is A

Step 1: Understand the problem gluconeogenesis creates.
Gluconeogenesis makes glucose from non-carbohydrate sources such as pyruvate and lactate, and several of its steps run in the cytosol. One of these steps, run by cytosolic glyceraldehyde-3-phosphate dehydrogenase acting in reverse, needs NADH in the cytosol. But most of the cell's reducing power sits inside the mitochondria as NADH, and the mitochondrial inner membrane will not let NADH cross directly.

Step 2: Recall how the cell gets around this barrier.
The cell uses a shuttle system. Oxaloacetate, made from pyruvate by pyruvate carboxylase inside the mitochondria, is reduced to malate using the mitochondrial NADH. Malate can cross the inner mitochondrial membrane through a specific transporter, something oxaloacetate itself cannot do efficiently.

Step 3: Follow malate once it reaches the cytosol.
In the cytosol, malate is oxidized back to oxaloacetate by cytosolic malate dehydrogenase, and this step regenerates NADH in the cytosol. This cytosolic NADH is then used to run the reductive steps of gluconeogenesis. In effect, malate has carried the reducing equivalents across the membrane on its back.

Step 4: Rule out the other options.
Aspartate and glutamate are part of the aspartate-glutamate arm of the general malate-aspartate shuttle used mainly to move reducing equivalents into mitochondria for oxidative phosphorylation, not the direction gluconeogenesis needs here, and they do not directly carry the reducing power out.
Oxaloacetate itself cannot cross the inner mitochondrial membrane through the main transporter used in this route, that is exactly the reason the cell first converts it to malate.

Step 5: Final answer.
The reducing equivalents needed in the cytosol for gluconeogenesis are exported from mitochondria in the form of malate.