- Flavin adenine dinucleotide (FAD) is a vital redox-active coenzyme involved in numerous metabolic processes within all forms of life. It functions primarily as an electron carrier, cycling between oxidized (FAD) and reduced (FADH₂) forms to facilitate redox reactions in biological systems.
- FAD is derived from riboflavin (vitamin B₂), which is first converted into flavin mononucleotide (FMN) and then further phosphorylated to form FAD. As a prosthetic group, FAD is tightly bound to various flavoproteins and enzymes, playing a critical role in energy production and cellular respiration.
- Structurally, FAD is composed of two nucleotide units: one containing an adenine base and the other a flavin mononucleotide. This dual structure allows FAD to participate in complex biochemical transformations. The isoalloxazine ring of the flavin moiety is particularly important, as it undergoes reversible reduction and oxidation, enabling FAD to accept and donate two electrons and two protons during metabolic reactions. In this way, FAD serves as a versatile coenzyme in redox reactions catalyzed by oxidoreductase enzymes.
- FAD is most notably involved in the mitochondrial electron transport chain and the citric acid (Krebs) cycle. For instance, in the Krebs cycle, FAD is a coenzyme for succinate dehydrogenase, the enzyme responsible for converting succinate to fumarate. In this process, FAD is reduced to FADH₂, which then donates electrons to the electron transport chain, ultimately contributing to ATP synthesis through oxidative phosphorylation. While NADH contributes more ATP per molecule, FADH₂ still plays a crucial role in cellular energy metabolism.
- Beyond energy production, FAD is essential in a variety of other biochemical reactions, including the metabolism of fatty acids, amino acids, and vitamins. It is also involved in the oxidative folding of proteins in the endoplasmic reticulum and the regulation of oxidative stress responses. As part of flavoproteins, FAD is associated with enzymes such as monoamine oxidases, xanthine oxidase, and glutathione reductase, which are key players in neurotransmitter breakdown, purine metabolism, and antioxidant defense.
- Deficiency in riboflavin, and consequently FAD, can impair these vital processes and lead to symptoms such as fatigue, inflammation of the skin and mucous membranes, and slowed metabolic function. While FAD itself is not taken as a supplement, maintaining adequate riboflavin intake through diet or supplementation ensures sufficient FAD synthesis within the body.
