Question

Acyl-CoA dehydrogenase uses enzyme-bound FAD as a prosthetic group to dehydrogenate the $a$ and $\beta$ carbons of fatty acyl-CoA. What is the advantage of using FAD as an electron acceptor rather than NAD ${}^{+}$? Explain in terms of the standard reduction potentials for the $\mathrm{Enz}-\mathrm{FAD}/{\mathrm{FADH}}_2(E^{\prime \circ }=-0.219\mathrm{V})$ and ${\mathrm{NAD}}^{+}/\mathrm{NADH}(E^{\prime \circ }=-0.320\mathrm{V})$ half- reactions.

Short answer

FAD's higher reduction potential (-0.219 V) makes it a better electron acceptor than NAD+ (-0.320 V), enabling efficient fatty acid oxidation.

Step-by-step solution

Understand the Reaction and Role of FAD

In the reaction catalyzed by Acyl-CoA dehydrogenase, FAD is used as a prosthetic group to accept electrons during the dehydrogenation of the α and β carbons of fatty acyl-CoA. This electron transfer is a crucial step in the metabolic breakdown of fatty acids.

Compare Standard Reduction Potentials

The standard reduction potential for the Enz-FAD/FADH2 pair is $E^{\prime \circ }=-0.219\text{V}$, while for the NAD+/NADH pair, it is $E^{\prime \circ }=-0.320\text{V}$. Standard reduction potentials indicate a molecule's tendency to gain electrons. A less negative potential suggests a stronger tendency to be reduced.

Analyze the Role of Reduction Potentials in Electron Transfer

FAD, with a reduction potential of -0.219 V, has a higher (less negative) standard reduction potential compared to NAD${}^{+}$ at -0.320 V. This higher potential makes FAD a more favorable electron acceptor in this specific enzymatic reaction, allowing the transfer of electrons to occur spontaneously under cellular conditions.

Interpret the Biological Advantage

Using FAD as an electron acceptor allows the dehydrogenation reaction to proceed efficiently, even in the absence of a broad variance in reactive potential between donor and acceptor. This efficiency is necessary for rapid energy conversion processes such as fatty acid oxidation in the mitochondrial matrix.

Key concepts

Acyl-CoA Dehydrogenase

Acyl-CoA dehydrogenase is a crucial enzyme in the process of fatty acid metabolism. Specifically, it catalyzes the dehydrogenation of acyl-CoA molecules. This means it helps strip away hydrogen atoms from fatty acids, ultimately breaking them down for energy production. The enzyme is an essential player in the initial step of beta-oxidation, a metabolic pathway where fatty acids are broken down into acetyl-CoA units, which can then enter the citric acid cycle. One of the key aspects of acyl-CoA dehydrogenase is its use of the cofactor FAD (flavin adenine dinucleotide). This cofactor is tightly bound to the enzyme and plays a pivotal role in accepting electrons from the acyl-CoA molecules, setting the stage for further reactions.

FAD

FAD, or flavin adenine dinucleotide, is a coenzyme often associated with various enzymatic reactions. It serves as a versatile electron acceptor in biochemical pathways, particularly during the beta-oxidation of fatty acids. As a cofactor for enzymes like acyl-CoA dehydrogenase, FAD undergoes reduction as it accepts two electrons and two protons to get converted into FADH₂. This transformation is crucial as it facilitates the transfer of stored energy within the cell. One of the reasons FAD is preferred in some reactions, such as in acyl-CoA dehydrogenase, is because of its less negative standard reduction potential compared to NAD⁺. This attribute makes it a more favorable electron acceptor in certain metabolic processes.

NAD⁺

NAD⁺ (nicotinamide adenine dinucleotide) is another coenzyme like FAD, but with distinct properties and roles in metabolism. It commonly functions in redox reactions where it alternates between its oxidized form, NAD⁺, and its reduced form, NADH. NAD⁺ plays a central role in catabolic reactions, where molecules are broken down to release energy. Its standard reduction potential is more negative than that of FAD, which signifies a greater degree of energy required to convert NAD⁺ to NADH compared to FAD to FADH₂. While NAD⁺ is a critical electron carrier in many biochemical pathways, its propensity to convert at a lower potential makes it less suited than FAD for reactions requiring spontaneous electron transfer, such as those catalyzed by acyl-CoA dehydrogenase.

Standard Reduction Potential

The standard reduction potential, denoted as E⁰', is a measure of the tendency of a chemical species to acquire electrons and be reduced. In simpler terms, it tells us how likely a molecule is to gain electrons under standard conditions. For instance, the Enz-FAD/FADH₂ pair has a standard reduction potential of -0.219 V. This value is less negative compared to the NAD⁺/NADH pair's potential of -0.320 V. A higher (less negative) reduction potential indicates a molecule's stronger predisposition to be reduced, thereby accepting electrons more readily. Consequently, in certain biological reactions, FAD is favored over NAD⁺ because its less negative potential promotes more spontaneous electron transfer.

Electron Transfer

Electron transfer is a fundamental process in numerous biochemical reactions, including oxidative phosphorylation and beta-oxidation. It involves the movement of electrons from a donor molecule to an acceptor. In the context of acyl-CoA dehydrogenase, electron transfer is crucial as FAD accepts electrons from the fatty acyl-CoA during the oxidation process. This transference sets off a chain of events leading to energy release through subsequent metabolic pathways. Efficient electron transfer is vital for quick and energy-sufficient conversions, especially in aerobic metabolism, where cells rely on oxygen to drive such processes. The suitability of FAD over NAD⁺ in certain reactions lies in how effectively it can drive these electron transfers, thanks to its standard reduction potential.