The search to identify these accessory food factors in milk, whole wheat, yeast, and liver began in the early 1900s.
McCollum and assistant Marguerite Davis produced three papers in 1915 which showed a diet containing 2% of wheat embryo or milk powder with polished rice, casein, salts, and butter fat provided enough of an ‘essential accessory’ to support growth of young rats.
The importance of lactochrome was not fully realized until later investigational studies by Elmer McCollum and Kennedy (1916), Emmett and Luros, and Smith and Hendrick that showed the preventive capabilities of water-soluble food extracts against beriberi, pellagra, and pellagra-like dermatitis.
Several years later, the physiological role of the yellow growth factor was shown by Warburg and Christian (1932) to be a component of a yeast “Zwischenferment,” which was designated the “old yellow enzyme.”
Joseph Goldberger in 1927 proposed there was an anti-pellagra factor in eggs, milk, etc., and it was the same substance as ‘water-soluble B’ identified by McCollum. Goldberger called the substance the pellagra-preventative or P-P dietary factor.
In 1935 Richard Kuhn at Heidelberg, and Paul Karrer at the University of Zurich eventually succeeded in synthesizing the vitamin, now termed riboflavin. They were awarded the Nobel Prize for this and other achievements in 1937 and 1938, respectively. Kuhn first proved that riboflavin is an essential growth factor, viz., vitamin B2.
Kuhn also developed a synthetic route to riboflavin which was licensed to the German company I. G. Farben.
Theorell in 1937 identified the isoalloxazine derivative from the old yellow enzyme as riboflavin-5′-phosphate, also called FMN (flavin mononucleotide). The structure of a second coenzymic form was established by Warburg and Christian (1938) as FAD (flavin adenine dinucleotide) and was shown to participate as the coenzyme of d-amino acid oxidase.
Discovery of riboflavin
