What is FAD?
Flavin Adenine Dinucleotide (abbreviated as FAD) is a biomolecule derived from riboflavin (vitamin B2). It is a coenzyme form of vitamin B2 used in clinical conditions regarding vitamin B2 deficiency. It is one of the forms of a flavoprotein, the other form being flavin mononucleotide (abbreviated as FMN).
Properties and Composition of FAD
- The chemical formula of Flavin Adenine Dinucleotide is C27H33N9O15P2
- It has a molar mass of 785.557 g·mol−1
- Its appearance is white and vitreous in the form of crystals
- It is also called riboflavin 5′-adenosine diphosphate
- Its IUPAC name is – ({(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxy oxolan-2-yl methoxy}(hydroxy)phosphoryl)oxy({(2R,3S,4S)-5-{7,8-dimethyl-2,4-dioxo-2H,3H,4H,10H-benzogpteridin-10-yl}-2,3,4-trihydroxy pentyloxy})phosphinic acid
- FAD exists in 4 redox states as follows :
- Flavin-N(5)-oxide: superoxidised form
- Quinone form (FAD): fully oxidised form
- Hydroquinone form (FADH2): formed when FAD in quinone form accepts 2 electrons and 2 protons to become FADH2 inon
- Semiquinone form (FADH): formed either by reduction of FAD or oxidation of FADH2
- It consists of 2 parts: adenine nucleotide (adenosine monophosphate) and the flavin mononucleotide (FMN) bridged together through phosphate groups, i.e., it’s a nucleotide composed of a nucleobase, a pentose, and phosphate group.
- It is autofluorescent and consists of an isoalloxazine ring connected to a ribityl adenine diphosphate.
Properties of states of FAD
FAD – Quinone form – fully oxidised: yellow, aromatic ring system
FADH – Semiquinone form – half reduced: blue or red in colour, is unstable in aqueous solution
FADH₂ – Hydroquinone form – fully reduced: colourless, has high polarizability, higher energy
flavin-N(5)-oxide: Superoxidised: yellow-orange in colour
Involvement in Metabolism Pathways
This molecule is involved in various metabolism pathways like –
- Glutathione Metabolism: this pathway involves the production of the antioxidant Glutathione, which plays important role in antioxidant defense, nutrient metabolism, and regulation of cellular events.
- Caffeine Metabolism: this pathway involves the metabolism of caffeine mainly through N-3-demethylation to paraxanthine, also known as 1,7-dimethylxanthine.
- Valine, Leucine, and Isoleucine Degradation: The catabolism of all three essential amino acids – Valine, Leucine, and Isoleucine starts in muscle, yielding NADH and FADH₂, which can be utilised for ATP generation.
- Lysine Degradation: it is a pathway confined to mitochondria, which proceeds through the formation of saccharopine.
- Folate Metabolism: this involves the production of Folates which are essential for the synthesis of DNA, the modification of DNA and RNA and various other chemical reactions involved in cellular metabolism.
- Riboflavin Metabolism: this takes place in gastrointestinal cells, where riboflavin is either metabolised to flavin mononucleotide (FMN) by riboflavin kinase (RFK) or to flavin adenine dinucleotide (FAD) by FAD synthase (FADS).
Processes that depend on FAD:
- Metabolism
- Bioenergetics
- Protein folding
- ROS production
- Defence against oxidative stress
- Redox epigenetics
- Cell differentiation
Clinical Significance of FAD:
- Flavoprotein-related diseases: riboflavin deficiency (and the resulting lack of FAD and FMN) can cause health issues. For example, in ALS patients, there are decreased levels of FAD synthesis.
- Drug design: in the design of antibacterial medications, a metabolic protein that uses FAD (Complex II) is vital for bacterial virulence. So targeting FAD synthesis or creating FAD analogues could be a useful area of investigation.
- Optogenetics: this is a process that allows control of biological events in a non-invasive manner, and for this, a number of new tools such as the Blue-Light-Utilising FAD domains (BLUF) have been major advancements.
- Treatment monitoring: the natural fluorescence of FAD allows Scientists to monitor disease progression or treatment effectiveness or aid in diagnosis in various cases like invasive oral cancer.
Conclusion:
Hence, we see that FAD is an integral part of various cellular processes in the human body and also that its deficiency leads to various diseases. Thus it is often used in the treatment of such clinical conditions.