Flavoprotein

Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin: the flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN).

Flavoproteins are involved in a wide array of biological processes, including, but by no means limited to, bioluminescence, removal of radicals contributing to oxidative stress, photosynthesis, DNA repair, and apoptosis. The spectroscopic properties of the flavin cofactor make it a natural reporter for changes occurring within the active site; this makes flavoproteins one of the most well studied enzyme families.

Discovery
The first mention of a flavoprotein in the scientific literature dates back to 1879, when the work on the composition of cow’s milk resulted in the isolation of a bright yellow pigment, that we now know as flavin, but termed lactochrome at the time. By the early 1930s this same pigment had been isolated from a range of sources, and recognised as a component of the vitamin B complex. Its structure was determined almost simultaneously by two groups in 1934, and given the name riboflavin, derived from the ribityl side chain and yellow colour of the conjugated ring system.

The first evidence for the requirement of flavin as an enzyme cofactor came in 1935. Hugo Theorell and coworkers showed that a brightly yellow coloured yeast protein, identified previously as essential for cellular respiration, could be separated into apoprotein and a bright yellow pigment. Neither apoprotein or pigment alone could catalyse the oxidation of NADH, but mixing of the two restored the enzyme activity. However, replacing the isolated pigment with riboflavin did not restore enzyme activity, despite the two being spectroscopically indistinguishable. This led to the discovery that the protein studied required not riboflavin, but flavin mononucleotide to be catalytically active

Similar experiments with D-amino acid oxidase led to the identification of flavin adenine dinucleotide (FAD) as a second form of flavin utilised by enzymes.