Flavins

FLAVINS (from Latin flavus - yellow), pigments of yellow color with intense green fluorescence. Due to their easy solubility in water, they are grouped together with the group of liochromes (Ehlinger, Koschara) in contrast to the fat-soluble lipochromes (see). Flavins are very widely, if not universally, distributed in nature, both in the plant and animal worlds, however occurring in very low concentrations. More closely studied are the flavins obtained from whey (lactoflavins), egg white (ovoflavins), liver (hepatoflavins), and further from malt, urine, various organs, etc. With flavins is identical the "cytoflav" isolated from cardiac muscle. By chemical structure, flavins belong to the quinoxaline type, being derivatives of isoalloxazine; with them is joined a residue of C₄H₈O₂ of carbohydrate-like structure. This residue under the influence of light in an alkaline medium is cleaved, giving the so-called photo-(or lumi-)flavins. Unlike native flavins, photo-flavins are soluble in chloroform; they preserve a spectrum of absorption close to the original flavin (^see Fig.). Artificial synthesis of photo-flavins was accomplished by Kuhn, who established its structure as trimethyl-alloxazine. Native flavin has the empirical formula C₁₇H₂₀N₄O₆ and the following structure: \ H₃C-C^xC^hC^hCH(CHOH)₂CH₂OH N₄ A \ CO H₃C-C^xC^hC^h ,.C^hJNH C^xN^xC^xC^h H₂O These data refer to lacto- and ovoflavins, which are apparently identical; the side chain in them by its structure corresponds to the configuration of ribose. Complete synthesis of such a flavin was accomplished almost simultaneously by Kuhn and Carrer. The question of to what extent other flavins differ from each other in their structure cannot yet be considered settled. Discovered and begun to be studied only in 1932, flavins have attracted great attention, since their diverse and very important biological functions were discovered. Thus, it turned out that flavins include vitamin B₂ (the heat-stable component of the vitamin B complex). There are grounds to believe that flavins to a certain extent serve as the active principle in liver preparations used for the treatment of anemia. On the other hand, flavins, upon joining phosphoric acid, constitute the active group of the so-called "second (yellow) respiratory enzyme" of Warburg. This enzyme is widely distributed in the animal and plant world, not only aerobic cells but also anaerobic microorganisms are rich in it. Its action is not inhibited by cyanides; in normal aerobic cells its share may account for only a small part of the total respiration, and Warburg attributes to it participation mainly in the processes of anaerobic oxidation and reduction. The enzymatic ability phosphorylated flavin acquires only as a result of combination with a special colloidal "carrier", which is a specific protein with globulin properties. When detached from this protein, flavins lose their enzymatic function but retain their vitamin function; upon recombination with protein, enzymatic properties are restored again. Heating destroys the enzymatic function without affecting the vitamin function. These relationships can be represented as follows: g Solubility in water as an oxidase vitamin enzyme form Flavins g a £ k я O + + + + The same heated - - + + Native flavin ..... + + - - + Irradiated flavin (lumiflavin) + + + -~ - Comparison of properties of liochromes (flavins) and lipochromes (carotenoids): Properties Liochromes (flavins) Lipochromes Color Yellow, orange, red Fluorescence .... Green, very Yellow-green, very strong weak Contain nitrogen Soluble in water Fat-soluble Insoluble Solubility Relation to acids . . Stable Labile to alkalis . Labile Stable Relation to B, Daily dose as vitamin.... 5.10^-6 g lacto- 2.5.10^-6 g caro- flavin tenoid In the free state, without a colloidal carrier, flavins can play the role of biological hydrogen acceptors, e.g. are capable of replacing methylene blue in experiments with anaerobic dehydrogenation of organic substances (lactic acid, aldehydes); under aerobic conditions they enhance the respiration of cells with low respiratory exchange (non-nucleated erythrocytes, lactic acid bacteria). As an oxidizing-reducing agent, flavins are distinguished by an extremely low potential: at pH=7 the normal potential E₀ = -0.227 volts, accordingly leuco-flavins are the strongest reducing agents. The transition from reduced to oxidized state and back occurs in two stages: first by monovalent reduction (correspondingly oxidation) a radical of semi-quinoid type (mono-hydro-connection) is formed, which in an acid medium is rather stable, with a bright red color. Only then does the formation of a stable form with an even number of electrons follow. V. Engelhardt.

In free form, without a colloidal carrier, flavins can play the role of biological hydrogen acceptors, for example, they are capable of replacing methylene blue in experiments with anaerobic dehydrogenation of organic substances (lactic acid, aldehydes); under aerobic conditions they enhance the respiration of cells with low respiratory exchange (non-nucleated erythrocytes, lactic acid bacteria). As an oxidizing-reducing agent, flavins are distinguished by an extremely low potential: at pH=7 the normal potential E₀ = -0.227 volts, accordingly leuco-flavins are the strongest reducing agents. The transition from reduced to oxidized state and back occurs in two stages: first by monovalent reduction (correspondingly oxidation) a radical of semi-quinoid type (mono-hydro-connection) is formed, which in an acid medium is rather stable, with a bright red color. Only then does the formation of a stable form with an even number of electrons follow. V. Engelhardt.