Effect of ring substituents on the transketolase-catalyzed conversion of nitroso aromatics to hydroxamic acids

Transketolase catalyzed the conversion of eight different aromatic C-nitroso compounds into the corresponding N-glycolyl derived hydroxamic acids. Three of the nitroso compounds were also found to be converted in part to the arylhydroxylamines by a reductive process. A correlation was found for the rates of production of these metabolites with the electronegativities of substituent groups that were present on the aromatic ring. The rates of reaction of these substituted nitroso substrates with transketolase and D-fructose-6-phosphate were found to decrease in the order 4-NO2 much greater than 4-CF3 greater than 3-CF3, unsubstituted greater than 4-Cl greater than 4-CH3, 4-phenyl greater than 4-OC2H5. N,N-Dimethyl-p-nitrosoaniline was not metabolized by transketolase under the conditions employed for the other substrates. Those substrates possessing the strong electron-withdrawing groups 4-NO2, 4-CF3 and 3-CF3 were the only substrates that were found to undergo enzymatic reduction to the hydroxylamines as a competing process. A mechanism was proposed that involves a redox reaction between the nitroso substrate and the enzymatic intermediate "active glycolaldehyde" at the active-site of transketolase.