Question

What are the major differences between the oxidations in the citric acid cycle that use \(\mathrm{NAD}^{+}\) as an electron acceptor and the one that uses FAD?

Short answer

\text{NAD}+ is used in three high-energy oxidations and has a higher electron affinity, while FAD is used in a lower-energy state oxidation linked to the membrane-bound succinate dehydrogenase complex.

Step-by-step solution

Identify the oxidations

In the citric acid cycle, there are four oxidation steps. Three of these use \(\text{NAD}^+\) as an electron acceptor, while one uses FAD.

Describe the \(\text{NAD}^+\) dependent oxidations

\(\text{NAD}^+\) dependent oxidations occur at three steps: isocitrate to \text{alpha}-ketoglutarate, \(\text{alpha}-ketoglutarate\) to succinyl-CoA, and malate to oxaloacetate. In these reactions, \(\text{NAD}^+\) is reduced to NADH.

Describe the FAD dependent oxidation

The FAD dependent oxidation occurs at the conversion of succinate to fumarate. In this reaction, FAD is reduced to FADH2.

Compare the electron acceptors

NAD+ and FAD differ in their reduction potentials; \(\text{NAD}^+\) has a higher affinity for electrons compared to FAD. This allows \(\text{NAD}^+\) to accept electrons at higher energy states in the cycle.

Analyze the cellular locations

The NAD+-dependent oxidations typically occur in the mitochondrial matrix, while the FAD-dependent oxidation is part of the inner mitochondrial membrane-bound succinate dehydrogenase complex.

Key concepts

NAD+ Dependent Oxidations

In the citric acid cycle, three key oxidation reactions utilize \(\text{NAD}^+\) as the electron acceptor. This molecule is crucial as it is reduced to form NADH. These reactions occur:

• Isocitrate to \(\text{alpha}\)-ketoglutarate
• \(\text{alpha}\)-ketoglutarate to succinyl-CoA
• Malate to oxaloacetate

In these transformations, \(\text{NAD}^+\) effectively picks up electrons, becoming NADH, which will later be used in other parts of cellular respiration to generate ATP. This is crucial as the transfer of these high-energy electrons helps drive the production of energy in the cell.

FAD Dependent Oxidation

Unlike the three reactions that use \(\text{NAD}^+\) as an electron acceptor, only one step in the citric acid cycle utilizes FAD. This reaction is the conversion of succinate to fumarate. During this process, FAD is reduced to form FADH2. FADH2 will later be used in the electron transport chain to help produce ATP.
This reaction is unique because FAD has different properties compared to \(\text{NAD}^+\). Specifically, FAD can accept electrons and protons at a different level of energy, allowing it to act in reactions where \(\text{NAD}^+\) is not suitable.

Reduction Potentials

Reduction potential refers to the tendency of a molecule to acquire electrons. In the citric acid cycle, \(\text{NAD}^+\) has a higher reduction potential compared to FAD. This means \(\text{NAD}^+\) has a greater affinity for electrons and can accept them at higher energy states.
This difference in reduction potentials is why \(\text{NAD}^+\) is involved in three reactions, while FAD is only involved in one. \(\text{NAD}^+\)'s ability to accept electrons at higher energy states makes it essential for capturing more energy from the substrates that are being oxidized in these reactions.

Mitochondrial Matrix

The mitochondrial matrix is the interior space of the mitochondria where many important processes occur, including most of the citric acid cycle. The matrix has a unique composition that supports the necessary reactions, including the \(\text{NAD}^+\)-dependent oxidations.
The enzymes involved in these reactions are found in the mitochondrial matrix, allowing close proximity to the reactions they catalyze. The production of NADH in the matrix is also advantageous as it can quickly enter the electron transport chain, aiding in efficient energy production.

Succinate Dehydrogenase Complex

The succinate dehydrogenase complex is a unique enzyme in the citric acid cycle. It is involved in the FAD-dependent oxidation of succinate to fumarate. Unlike other enzymes in the citric acid cycle, this complex is embedded in the inner mitochondrial membrane.
This location is strategic because the FADH2 produced can directly enter the electron transport chain. The succinate dehydrogenase complex plays a dual role in linking the citric acid cycle and the electron transport chain, making it essential for cellular respiration and efficient ATP production.