Flavin oxidized

A current overall picture of the reaction mechanism of xanthine oxidase, which differs substantially from one proposed earlier (87) is as follows. The enzyme is presumed to have two independent catalytic units, though this has not so far been proved rigorously. Reducing substrates are bound at molybdenum and reduce this from Mo(VI) both to Mo(V) and to Mo (IV). Reducing equivalents are then transferred by intramolecular reactions from molybdenum to iron-sulphur and also, either directly or via this, to flavin. Oxidizing substrates as a class, seem capable of reacting with all three types of centre in the enzyme. Thus, oxygen reacts predominantly with flavin, phenazine methosulphate... 

The conversion (19) of thiols to disulphides coupled with reduction of flavin (vitamin B2 family) is a topic of import in connection with coenzyme reactivity in flavoenzymes. Since flavin oxidation of thiols involves nucleophilic attack of thiolate ion in the rate-determining step (Loechler and Hollocher, 1975 Yokoe and Bruice, 1975), this biologically important reaction would be markedly affected by hydrophobic environments. 

Flavin oxidation of carbanions has also been of much concern since active intermediates in some flavoenzyme-mediated reactions (amino acid oxidase, lactate oxidase, etc.) are carbanions (Kosman, 1977). Flavin oxidation of nitroethane carbanion (20), which had not been achieved in non-enzymatic systems, occurs with [56] bound to CTAB micelles (Shinkai etal., 1976b). This suggests that the nitroethane carbanion is also activated by the micellar environment. 

The combination of cyanide ion with flavin provides a novel flavin oxidation... 

That the expression (fcHo[HO-] + fcgb[B])[CH] pertains to the rate of carbanion formation is established under conditions of high [Flox] when carbanion formation is rate determining. Under this condition, the rate constant for the flavin oxidation of dimethyl trans-1,2-dihydrophthalate to dimethyl phthalate is identical to the rate constant for base-catalyzed isomerization of the substrate to its 1,4-isomer (Equation 15) (8). This flavin oxidation serves as abiomimetic reaction... 

Having shown that general-base-catalyzed carbanion formation precedes the oxidation step in flavin oxidation of the second class of carbon acids, the question arises as to how the electron pair moves from the carbanion to flavin. Covalent addition of carbanion to Flox followed by a base-catalyzed elimination reaction is one possibility (13). Addition to the 4a- (Equation 17) and 5-position (Equation 18) would appear to be feasible and, a priori, it would seem reasonable to expect that these adducts could undergo an elimination to yield oxidized substrate and reduced flavin. Nucleophilic addition of SO J to... 

Cameron and Aust have examined the electron-transfer processes between the two domains using EPR and stopped-flow spectroscopy. FAD was found to be the direct electron donor for the transfer of electrons to all substrates tested, including cytochrome c. A comphcated interaction was found to exist between the FAD and heme cofactors. The addition of electron acceptors was shown to increase the rate of flavin oxidation and the electron-transfer rate between the flavin and heme, although the heme itself was not involved in the direct transfer of electrons to substrate. 

Bruice, T. C., and Taulane, J. P., 1976, The kinetics and mechanisms of 1,5-dihydroflavin reduction of carbonyl compounds and flavin oxidation of alcohols. 3. Oxidation of benzoin by flavin and reduction of benzil by 1,5-dihydroflavin, /. Am. Chem. Soc. 98 7769. 

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