What is the Difference Between FAD and FADH2

The main difference between FAD and FADH2 is that FAD is the oxidized form of the FAD molecule, whereas FADH2 is the reduced form of the FAD molecule.

Co-enzymes are organic compounds that facilitate the action of enzymes and can bind permanently or temporarily to an enzyme. These co-enzymes can catalyze reactions, but when they combine with an enzyme, their catalytic effect is higher. Furthermore, co-enzymes have many different functions. Some of them include facilitating reactions by associating with enzyme substrates at enzyme active sites, acting as carriers of hydrogen atoms, electrons, or chemical groups, and assisting in intracellular energy coupling reactions. Moreover, some examples of co-enzymes are thiamine pyrophosphate (TPP), lipoic acid (LA), free CoA, and flavin adenine dinucleotide(FAD).

Key Areas Covered  

1. What is FAD
     – Definition, Composition, Features
2. What is FADH2
     – Definition, Composition, Features
3. Difference Between FAD and FADH2
     – Comparison of Key Differences

Key Terms

FAD, FADH2, Flavin Adenine Dinucleotide

What is FAD

FAD is a type of co-enzyme. FAD is the shorthand for flavin adenine dinucleotide. It has a moecular formular of C₂₇H₃₃P₂N₉O₁₅ and a molar mass of 785.5497 g/mol. Moreover, it is an important redox cofactor of several reactions. Furthermore, FAD is formed from a riboflavin moiety (vitamin B2) coupled to a phosphate group of an ADP molecule. First, the conversion reaction of riboflavin to riboflavin mononucleotide is catalyzed by riboflavin kinase. Then the flavin mononucleotide is transformed into FAD by the addition of an ATP moiety from ATP. The enzyme catalyzing the reaction here is FAD synthase. Riboflavin (vitamin B12) acts as a precursor in this reaction. Here, riboflavin covalently links with adenine diphosphate.

Besides, FAD is an organic molecule that carries electrons. It participates in many chemical reactions due to this electron-carrying ability. It has a flavin backbone, two phosphate groups, ribose, and an adenine. Also, this molecule has the ability to participate in a wide range of oxidation and reduction reactions due to its ability to donate or accept one or two electrons, as well as in lyase and transferase reactions, to a smaller extent.

FAD can exist in three forms. They are the oxidized form, reduced form, and intermediate semiquinone. The oxidized form has no hydrogens at positions N1 and N5. (FAD). The reduced form has hydrogens at both positions, N1 and N2. (FADH2). The immediate semiquinone has one hydride ion at one of the positions(FADH- radical). Furthermore, the regeneration of FAD to its original form in the protein is possible by the external redox molecules.

What is FADH2

FAD is a redox cofactor that is created during Kreb’s cycle. It is then utilized in the last part of respiration. Its molecular formula is C₂₇H₃₅N₉O₁₅P₂, and its molecular weight is 787.6. This is the hydroquinone form of FAD. Flavin adenine dinucleotide consists of two parts. They are the flavin mononucleotide and the adenine nucleotide (adenosine monophosphate ). Moreover, the phosphate groups bind these two parts together.

FAD can be reduced to FADH2 by the addition of 2 H+ and 2 electrons. It can be oxidized by the loss of one H+ and one electron to form FADH. Moreover, the recreation of the FAD form involves losing one H+ ion and one electron. According to the state of oxidation or reduction, these flavins take different colors in the aqueous solution. FAD, the fully oxidized form, is yellow, whereas the fully reduced form is colorless. This change in the form of flavins has a contrasting impact on other chemical properties. For example, the fully reduced form, that is, the FADH2 form has high polarizability.

FADH2 is not in an aromatic ring system form though the FAD is in such form. This implies that FADH2 is high in energy without stabilizing via the resonance structures of aromatic rings. FADH2 molecule carries energy. Once it oxidizes, it gains stability through aromaticity. This releases a large amount of energy.

Difference Between FAD and FADH2

Definition

FAD is the oxidized form of the FAD molecule, whereas FADH2 is a reduced form of the FAD molecule.

Presence of Stable Resonance Structures

FAD has stable resonance structures, while FADH2 does not have stable resonance structures.

Stability

Moreover, FAD is a more stable molecule than FADH2.

Energy

The energy in the FAD molecule is lower, whereas the energy in the FADH2 molecule is comparatively higher.

Oxized vs Reduced

FAD is the oxidized form, whereas FADH2 is the reduced form.

Color in the Aqueous Solution

FAD is yellow in its aqueous form, while FADH2 is colorless in its aqueous form.

Gain or Release of Electrons

While FAD gains electrons and hydrogen to become FADH2, FADH2 releases electrons and hydrogen to become FAD.

Conclusion

Co-enzymes are organic compounds that facilitate the action of enzymes and which can bind permanently or temporarily to an enzyme. There are many types of co-enzymes, and FAD and FADH2 are two of them. The main difference between FAD and FADH2 is that FAD is the oxidized form of the FAD molecule, whereas FADH2 is the reduced form of the FAD molecule.

Reference:

1. “Flavin Adenine Dinucleotide – Overview.” Science Direct.
2. “Dihydroflavine-adenine dinucleotide.” PubChem. National Library of Medicine.

Image Courtesy:

1. “FAD Synthesis” By Gk2015 – Own work (CC BY-SA 4.0) via Commons Wikimedia
2. “FADH2 production by flavin reductase for HOCl generation and halogenase activity” By Jmont31 – Diagram made with ChemDraw (CC BY-SA 4.0) via Commons Wikimedia