Fructation Induces Hemin Degradation in Methemoglobin

Abstract

Under prolonged diabetic conditions, HbA_1c is produced from normal hemoglobin (HbA₀) through a non-enzymatic glycosylation or glycation, a process which enhances the hemoglobin susceptibility to be auto-oxidized to methemoglobin (metHb). Here we are reporting that the non-enzymatic reaction between fructose and metHb (metHb fructation) induces significant changes in the globin structure and degrades the hemin moiety. Moreover, glycation of metHb by fructose brings about the extensive hypochromic effect and a small bathochromic effect in the Soret region. The products of hemin degradation were shown to be dialyzable species. Cathodic peaks of the cyclic voltammogram (CV) of methemoglobin during incubation with fructose resulted positive potential shift and the declined current at the peaks due to a decrease in the number of metHb molecules with the preserved hemin groups. Moreover, we found a significant increase in the hemin oxidation products such as ferryl/oxoferryl-Hb upon fructation of metHb. The production of such species during metHb fructation and hemin degradation might have a key role not only in the induction of hypoxic stress, but also in the reduced protective function of neural hemoproteins in Alzheimer's disease (AD).