Question

Use of FAD Rather Than NAD \(^{+}\)in Succinate Oxidation All the dehydrogenases of glycolysis and the citric acid cycle use \(\mathrm{NAD}^{+}\left(E^{\prime \circ}\right.\) for \(\mathrm{NAD}^{+} / \mathrm{NADH}\) is \(\left.-0.32 \mathrm{~V}\right)\) as electron acceptor except succinate dehydrogenase, which uses covalently bound \(\mathrm{FAD}\left(E^{\prime \circ}\right.\) for \(\mathrm{FAD}^{+} / \mathrm{FADH}_{2}\) in this enzyme is \(0.050 \mathrm{~V}\) ). Suggest why FAD is a more appropriate electron acceptor than \(\mathrm{NAD}^{+}\)in the dehydrogenation of succinate, based on the \(E^{\prime \circ}\) values of fumarate/succinate \(\left(E^{\prime \circ}=0.031 \mathrm{~V}\right), \mathrm{NAD}^{+} / \mathrm{NADH}\), and the succinate dehydrogenase \(\mathrm{FAD} / \mathrm{FADH}_{2}\).

Short answer

FAD is more suitable due to its reduction potential closer to fumarate/succinate, facilitating efficient electron transfer.

Step-by-step solution

Understand Standard Reduction Potentials

First, let's define the standard reduction potential (\( E'^{\circ} \)). It is a measure of the tendency of a chemical species to acquire electrons and thereby be reduced. Here we have: \( \mathrm{NAD}^{+}/\mathrm{NADH} \) with \( E'^{\circ} = -0.32 \text{ V} \), \( \mathrm{FAD}/\mathrm{FADH}_2 \) in succinate dehydrogenase with \( E'^{\circ} = 0.050 \text{ V} \), and \( \text{fumarate/succinate} \) with \( E'^{\circ} = 0.031 \text{ V} \).

Compare Reduction Potentials

Next, compare the standard reduction potentials of \( \mathrm{FAD}/\mathrm{FADH}_2 \) and \( \mathrm{NAD}^{+}/\mathrm{NADH} \) with that of \( \text{fumarate/succinate} \). The \( E'^{\circ} \) for \( \text{fumarate/succinate} \) is closer to \( \mathrm{FAD}/\mathrm{FADH}_2 \) (0.031 V versus 0.050 V) than to \( \mathrm{NAD}^{+}/\mathrm{NADH} \) (-0.32 V). This proximity indicates that \( \mathrm{FAD} \) is better suited to act as an electron acceptor in this reaction context.

Analyze Energetic Favorability

According to the standard reduction potentials, the energy yield of transferring electrons from succinate to \( \mathrm{NAD}^{+} \) would be too low to drive the reaction efficiently (because of the large difference between 0.031 V and -0.32 V). However, using \( \mathrm{FAD} \) with \( E'^{\circ} = 0.050 \) V results in a smaller potential difference (0.050 V - 0.031 V), allowing for a feasible redox reaction energetically.

Conclude the Suitability of FAD

Due to the closer match in reduction potential values between \( \text{fumarate/succinate} \) and \( \mathrm{FAD}/\mathrm{FADH}_2 \), \( \mathrm{FAD} \) is more effective than \( \mathrm{NAD}^{+} \) for accepting electrons in this specific biochemical reaction, facilitating a more energetically favorable electron transfer process.

Key concepts

Standard Reduction Potential

The standard reduction potential, denoted as \( E'^{\circ} \), is a vital concept in understanding electron transfer reactions. It indicates how readily a molecule can gain electrons, essentially becoming reduced. A higher \( E'^{\circ} \) signifies a greater tendency to accept electrons.
For example, in the biochemical context provided, we have specific \( E'^{\circ} \) values:

• \( \mathrm{NAD}^{+}/\mathrm{NADH} \): \(-0.32\text{ V} \)
• \( \text{fumarate/succinate} \): \(0.031 \text{ V} \)
• \( \mathrm{FAD}/\mathrm{FADH}_2 \) with succinate dehydrogenase: \(0.050 \text{ V} \)

These values help determine which compounds are likely to participate in successful electron transfers. In reactions like succinate oxidation, choosing an electron acceptor with a matching \( E'^{\circ} \) ensures efficient energy transfer and minimizes energy waste.

Electron Acceptor

In biochemical processes, electron acceptors play a pivotal role in facilitating redox reactions. An electron acceptor is a molecule that receives or "accepts" electrons transferred during the reaction. The ability of a molecule to act as an electron acceptor depends largely on its standard reduction potential.
In the case of succinate oxidation, \( \mathrm{FAD} \) is the chosen electron acceptor because its \( E'^{\circ} \) is closer to that of fumarate/succinate. This proximity in values means \( \mathrm{FAD} \) can effectively receive electrons from succinate, making the reaction more feasible energetically. On the contrary, \( \mathrm{NAD}^{+} \) with a much lower \( E'^{\circ} \) of -0.32 V does not match well with fumarate/succinate’s 0.031 V, resulting in lower energetic favorability.

Succinate Dehydrogenase

Succinate dehydrogenase is an enzyme involved in the citric acid cycle, playing a unique dual role as it participates in both the citric acid cycle and the electron transport chain. It facilitates the conversion of succinate to fumarate, a critical step in energy production within cells.
What sets succinate dehydrogenase apart is its use of \( \mathrm{FAD} \) as a covalently-bound electron acceptor. As part of this enzyme, \( \mathrm{FAD} \) helps drive the oxidation of succinate to fumarate effectively, aided by the favorable standard reduction potential between \( \mathrm{FAD} \) and fumarate/succinate. This connection intricately links the function of succinate dehydrogenase to efficient cellular respiration and energy production.

FAD vs NAD+

FAD and NAD+ are both crucial electron carriers in cellular metabolism, but they have distinct roles and preferences based on their reduction potentials. \( \mathrm{FAD} \) has a standard reduction potential of 0.050 V, while \( \mathrm{NAD}^{+} \) has a much more negative potential of -0.32 V.
In the context of succinate oxidation, \( \mathrm{FAD} \) is preferred due to its higher affinity for electrons in reactions where the electron donor’s \( E'^{\circ} \) is similar, such as fumarate/succinate. Meanwhile, \( \mathrm{NAD}^{+} \) is utilized in other dehydrogenase reactions where its potential aligns with other substrates. This difference optimizes energy transfer processes across various metabolic pathways, ensuring each molecule is used where its electron shuttling capabilities are most advantageous. Understanding these differences is key to grasping why specific carriers are used in different biochemical scenarios.