Semiquinone formation

Edmondson, D. E., and Tollin, G. Semiquinone Formation in Flavo- and Metalloflavoproteins. 

Table 1. Potentials Ej and EjCV) of i in acetonitrile vs. Ag/AgCl/CH N. = Semiquinone formation constant ( ) = irreversible...

Table 11. Comparison of semiquinone formation constants K m of iso-7r-electronic redox systems of the general types A, B and C in DMF versus Ag/AgQ in acetonitrile...

The metal chelating ability of flavins has been extensively investigated predominately in Hemmerich s laboratory While the oxidized and reduced (hydroquinone) forms of flavin are poor chelating ligands to divalent metal ions in aqueous solution, the flavin semiquinone forms chelates of considerable stability. This is readily demonstrated by the increase in semiquinone formation on the addition of metal ions to a half-reduced flavin solution which occurs by shifting the equilibrium away from semiquinone dismutation ... 

The properties of the semiquinone from of the ETF isolated from the methylotrophic bacterium resemble those of the bacterial flavodoxins with the exception that flavodoxins form neutral semiquinones whereas this ETF forms an anionic semiquinone. Nearly quantitative anionic semiquinone formation is observed either in the presence of excess dithionite or when excess trimethylamine and a catalytic amount of trimethylamine dehydrogenase are added. Of interest is the apparent stability of the anionic semiquinone towards oxidation by O2 but not to oxidizing agents such as ferricyanide. This appears to be the first example of an air-stable protein-bound anionic flavin semiquinone. Future studies on the factors involved in imparting this resistance to O2 oxidation by the apoprotein are looked forward to with great interest. 

A considerable amount of information regarding flavin semiquinone reactivity as well as the environment of the bound flavin coenzyme has accumulated over the years from studies of flavoenzyme systems which produce semiquinones either on photochemical reduction or upon reduction by one electron equivalent of dithionite, but which do not form a detectable semiquinone intermediate during catalytic turnover. For example, the correlation of anionic semiquinone formation and the ability to bind sulfite at the N(5) position in a number of flavoenzyme... 

In the case of two flavoenzyme oxidase systems (glucose oxidase (18) and thiamine oxidase s where both oxidation-reduction potential and semiquinone quantitation values are available, semiquinone formation is viewed to be kinetically rather than thermodynamically stabilized. The respective one-electron redox couples (PFl/PFl- and PFI7PFIH2) are similar in value (from essential equality to a 50 mV differential) which would predict only very low levels of semiquinone (32% when both couples are identical) at equilibrium. However, near quantitative yields (90%) of semiquinone are observed either by photochemical reduction or by titration with dithionite which demonstrates a kinetic barrier for the reduction of the semiquinone to the hydroquinone form. The addition of a low potential one-electron oxidoreductant such as methyl viologen generally acts to circumvent this kinetic barrier and facilitate the rapid reduction of the semiquinone to the hydroquinone form. 

Semiquinone formation is undoubtedly of great significance in physiological processes. Thus it has been found64 that whereas diamino-durene. increases the respiration of erythrocytes to about the same extent as methylene blue, tetramethyldiaminodurene has no catalytic effect at all. 

Figure 6. Scheme to represent known aspects of the plasma membrane NADH oxidase and its association with proton release. The oxidase is activated when hormones or ferric transferrin bind receptors. Oxidase may activate tyrosine kinase which can activate MAP kinases to result in phosphorylation of the exchanger leading to Na+/H+ exchange. Oxidation of quinol in the membrane can also release protons to the outside equal to the number of electrons transferred. External ferricyanide can activate electron flow by accepting electrons at the quinone. G proteins (GTP binding proteins) such as ras-activate electron transport and proton release in some way and may be a link to kinase activation (McCormick, 1993). Semiquinone formation in the membrane could lead to superoxide and peroxide formation by one electron reduction of oxygen. 

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