Oxidative Phosphorylation 2: Study with Video Lessons, Practice Problems & Examples

Cytosolic NADH from glycolysis can yield either 3 or 5 ATP depending on the transport mechanism into the mitochondria. The Glycerol 3 Phosphate shuttle produces 3 ATP by transferring electrons to FAD, bypassing complex 1, while the Malate-Aspartate shuttle yields 5 ATP by transporting NADH without energy cost. This shuttle involves malate dehydrogenase converting oxaloacetate to malate, which enters the matrix and is reoxidized, regenerating NADH. Aspartate is formed and transported back to the cytosol, completing the cycle and efficiently transferring electrons into the mitochondrial matrix.

Oxidative Phosphorylation 2

You might recall that cytosolic NADH produced by glycolysis can lead to the production of 3 or 5 ATP depending on the method used. So, NADH will actually only lead to the production of 3 ATP if it passes its electrons to an FAD via mitochondrial glycerol-3-phosphate dehydrogenase. The way this works is basically NADH will oxidize to NAD⁺ in the process of reducing dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphates. It's important to mention that this is glycerol-3-phosphate, not to be confused with glyceraldehyde-3-phosphate, which is often abbreviated as G3P. Glycerol-3-phosphate will then reduce FAD to FADH₂, and this passes its electrons onto ubiquinone, which will, of course, pass them on to complex 3. Essentially, in this process, complex 1 is bypassed entirely. Because complex 1 normally is where NADH drops off its electrons, bypassing it means missing out on some proton pumping. However, it's important to note that the electrons are not entering through complex 2 but through glycerol-3-phosphate dehydrogenase, a peripheral protein that passes those electrons to the quinone, enabling them to reach complex 3.

The other way that NADH can get its electrons into the mitochondria is through the malate aspartate shuttle, which yields 5 ATP. The malate aspartate shuttle transports NADH across the mitochondrial membrane at no energy cost, similar to the NADHs generated in the citric acid cycle which already occurs in the mitochondria. This process involves malate dehydrogenase in the cytosol reducing oxaloacetate (OAA) using NADH, converting it to NAD⁺ and forming malate. Malate then gets transported into the matrix where it is reoxidized back to oxaloacetate while reducing NAD⁺ to NADH. Here, oxaloacetate will be converted to aspartate by adding an amino group transferred from glutamate, turning it into alpha-ketoglutarate.

The interesting part is the transport mechanism, where the malate-aspartate transporter—an antiporter—swaps malate into the matrix for alpha-ketoglutarate moving into the cytosol. The transformative effect of converting oxaloacetate to aspartate uses the product of the aforementioned antiporter reaction. Aspartate then also travels through an antiporter back into the cytosol where it converts into oxaloacetate once again, picking up the amino group from alpha-ketoglutarate to reform glutamate. This continuous cycle is crucial in transferring NADH's electrons into the mitochondrial matrix efficiently. Lastly, the aspartate transporter, another antiporter, takes in glutamate and exports aspartate from the mitochondrial matrix. This cycle, though complex, is vital for the internal electron transport chain functioning. With that comprehensive explanation, let's turn the page.

Here’s what students ask on this topic:

What is the difference between the Glycerol 3 Phosphate shuttle and the Malate-Aspartate shuttle in oxidative phosphorylation?

The Glycerol 3 Phosphate shuttle and the Malate-Aspartate shuttle are two mechanisms for transporting cytosolic NADH into the mitochondria. The Glycerol 3 Phosphate shuttle transfers electrons from NADH to FAD, producing FADH₂ and bypassing complex I, resulting in the production of 3 ATP. In contrast, the Malate-Aspartate shuttle transports NADH directly into the mitochondrial matrix without energy cost, yielding 5 ATP. This shuttle involves converting oxaloacetate to malate, which enters the matrix and is reoxidized to regenerate NADH. Aspartate is then formed and transported back to the cytosol, completing the cycle.

How does the Glycerol 3 Phosphate shuttle affect ATP yield in oxidative phosphorylation?

The Glycerol 3 Phosphate shuttle affects ATP yield by transferring electrons from cytosolic NADH to FAD, forming FADH₂. This process bypasses complex I of the electron transport chain, which normally pumps protons to generate a proton gradient. As a result, fewer protons are pumped, leading to the production of only 3 ATP per NADH molecule instead of the usual 5 ATP. This reduction occurs because FADH₂ contributes fewer protons to the gradient compared to NADH.

Why does the Malate-Aspartate shuttle yield more ATP than the Glycerol 3 Phosphate shuttle?

The Malate-Aspartate shuttle yields more ATP than the Glycerol 3 Phosphate shuttle because it transports NADH directly into the mitochondrial matrix without energy cost. This shuttle involves converting oxaloacetate to malate, which enters the matrix and is reoxidized to regenerate NADH. The NADH produced in the matrix can then enter the electron transport chain at complex I, leading to the production of 5 ATP. In contrast, the Glycerol 3 Phosphate shuttle transfers electrons to FAD, bypassing complex I and resulting in only 3 ATP.

What role does malate dehydrogenase play in the Malate-Aspartate shuttle?

Malate dehydrogenase plays a crucial role in the Malate-Aspartate shuttle by catalyzing the conversion of oxaloacetate to malate in the cytosol using NADH. This reaction reduces NADH to NAD⁺. Malate is then transported into the mitochondrial matrix, where it is reoxidized back to oxaloacetate, regenerating NADH. This NADH can then enter the electron transport chain at complex I, contributing to ATP production. The shuttle efficiently transfers electrons from cytosolic NADH into the mitochondrial matrix, facilitating oxidative phosphorylation.

How does the antiporter system work in the Malate-Aspartate shuttle?

The antiporter system in the Malate-Aspartate shuttle involves two key antiporters. The first antiporter transports malate into the mitochondrial matrix while simultaneously exporting α-ketoglutarate to the cytosol. Once inside the matrix, malate is reoxidized to oxaloacetate, regenerating NADH. The second antiporter moves aspartate out of the matrix and imports glutamate. Aspartate is then converted back to oxaloacetate in the cytosol, completing the cycle. This system ensures efficient electron transfer from cytosolic NADH to the mitochondrial matrix, facilitating ATP production.