Biochemistry - The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

Coenzymes - specialized natural reagents
Flavin coenzymes
Flavoproteins and their redox potentials

Flavin Coenzymes are typically tightly bound to Proteins, cycling between reduced and oxidized states while remaining attached to the same protein molecule. What determines the reduction potential of a flavin within such a flavoprotein? The Redox Potential of the free coenzyme depends on the structures of the oxidized and reduced forms of the respective pair. Both riboflavin and pyridine nucleotide molecules contain aromatic ring systems stabilized by Resonance. Upon reduction, this resonance is partially (though not entirely) lost. The value of E⁰' depends on the degree of resonance in the oxidized and reduced forms and on any factors that preferentially stabilize one of these forms. The structures of these coenzymes are finely tuned to provide E⁰' values optimal for carrying out biological Functions.

Differences in the relative binding affinities of the oxidized and reduced forms of flavin coenzymes to the protein exert a profound and distinct influence on the reduction potential. If the oxidized form binds weakly and the reduced form binds strongly, the bound flavin will have a greater tendency to transition into the reduced form compared to the free coenzyme. Consequently, the reduction potential E^0' will be less negative than that of the free flavin/dihydroflavin pair. Conversely, if the oxidized flavin form binds to the protein more tightly than the reduced form, the E^0' value will become more negative, making the flavoprotein a weaker oxidizing agent than free riboflavin. In fact, the E⁰' values (at pH 7) of Flavoproteins span an unusually wide range—from -0.49 to +0.19 V.

It is worth noting that each flavoprotein accepts electrons from an oxidizable substrate and transfers them to another substrate, an oxidant. This is one of the main reasons why the chemistry of flavoproteins is so remarkably diverse. To fully characterize a flavoprotein, we must understand how electrons are transferred from the oxidizable substrate to the flavin, how they are subsequently released from the flavin, and what compound serves as the final electron acceptor.