Reactivity of 6-phosphogluconolactone with hydroxylamine: the possible involvement of glucose-6-phosphate dehydrogenase in endogenous glycation reactions.

The reactivity of 6-phosphogluconolactone and of delta-gluconolactone with hydroxylamine (a model compound in electrophilicity determination studies) was examined and compared with the reactivity of several other electrophiles, such as acid anhydrides and esters, some of which exhibit adverse biological effects (e.g. carcinogenicity). At pH 7.6 and 30 degrees C, and with an excess of hydroxylamine concentration, most of the compounds tested disappear from the medium in a monoexponential reaction. On the other hand, the reaction of 6-phosphogluconolactone with hydroxylamine is biexponential. This finding indicates the existence of 6-phosphogluconolactone in two interconvertible, isomeric forms. The reactivity, towards hydroxylamine, of 6-phosphogluconolactone and, to a lesser extent of delta-gluconolactone, is on the upper scale of reactivity of the electrophiles tested. It is concluded that 6-phosphogluconolactone (and in particular, one of its isomeric forms) is a highly electrophilic compound, and may possibly react with sundry intracellular nucleophiles, thereby exerting untoward metabolic effects. In this connection, it is of interest that a positive correlation has been found to exist between glucose-6-phosphate dehydrogenase activity and cell proliferation.