Hydroperoxides flavin

Figure 27.13 Proposed mechanism of the oxidation of squalene by flavin hydroperoxide.

These include the mitochondrial respiratory chain, key enzymes in fatty acid and amino acid oxidation, and the citric acid cycle. Reoxidation of the reduced flavin in oxygenases and mixed-function oxidases proceeds by way of formation of the flavin radical and flavin hydroperoxide, with the intermediate generation of superoxide and perhydroxyl radicals and hydrogen peroxide. Because of this, flavin oxidases make a significant contribution to the total oxidant stress of the body. 

The BDE value for tricyclic flavin hydroperoxide is taken from Reference 20c. 

There is good evidence from 13C NMR and electronic spectra for an enzyme-bound reduced flavin hydroperoxide as in Eq. 15-31. While this hydroperoxide can decompose slowly to flavin and H202 in the dark, it can also carry out the oxidation of the aldehyde with emission of light.685/685a The luminescent emission spectrum resembles the fluorescence spectrum of the 4a -OH adduct (Eq. 23-49), which is probably the light-emitting species.686-688... 

The mechanism suggested in Ref. [129] does not imply the formation of an intermediate product with an open ring. Active oxaziridine-4a,5-flavin benzoxide formed from flavin hydroperoxide is assumed to be the intermediate. This mechanism based on the electrophilic type of the oxaziridine system is justified in multiple examples, united in the following diagram [128] ... 

S-oxidation of thioxane by 4a-FlEtOOH in anhydrous dioxane is first order in the flavin hydroperoxide (35). Apparently the oxygen atom transfer potential of 4a-FlEtOOH is such that general-acid-catalyzed assistance of oxygen transfer is not required. 

The mechanisms for passage of electrons out of the cosubstrate undergoing oxidation and into the flavin undergoing reduction have been scrutinized carefully in the past decade, as have those for reoxidation of flavin and passage of electrons to the cosubstrate that experiences net reduction. Depending on substrate structure a variety of covalent intermediates have been postulated or demonstrated directly thus 02 reacts with dihydroflavins to form 4a flavin hydroperoxides IV... 

The bioluminescence of certain bacteria appears to involve the reaction of a flavin hydroperoxide with an aldehyde. This reaction proceeds through one or... 

Flavin semiquinone and superoxide react to form flavin hydroperoxide flavin-Fl + 02 - flavin-HOOH... 

Flavin hydroperoxide slowly breaks down to yield flavin semiquinone and perhydroxyl flavin-HOOH flavin-H -1- OjH Perhydroxyl decays to superoxide plus a proton... 

Because the 4a-flavin hydroperoxides are intermediates in both flavoprotein oxidase and mono-oxygenase chemistry/7 possible mechanisms for their formation are fundamental to an understanding of their biogenesis. 

A variation on this model has recently been proposed by Kelly et al. who suggested that the hydroxy group of the Criegee intermediate could not be immobilized in such a mechanism, and that unreasonable steric constraints would be imposed for many of the substrates transformed reported for these enzymes. A new tautomer of the the flavin hydroperoxide was proposed as part of an alternative scheme (lower cycle, Fig. 16.5-16) in which an intermediate trioxane decomposes to yield the lactone and flavin hydrate. 

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