Oxidative alterations in the experimental glycation model of diabetes mellitus are due to protein-glucose adduct oxidation : some fundamental differences in proposed mechanisms of glucose oxidation and oxidant production

摘要: Modification of human serum albumin (HSA) with formaldehyde resulted in a loss 75% available lysine residues, but there was no change histidine content or susceptibility to free-radical-mediated fragmentation. The modified HSA appeared resistant glycation and glucose-mediated Native inhibited oxidant production by free glucose, as assessed the hydroxylation benzoic acid, had little effect. Thus oxidation glucose be glycatable protein, not unglycatable protein. Also, close proximity protein (decreased case HSA) would seem prerequisite for This latter observation, particular, led us examine role attached reactive oxidants subsequent molecular damage. Glycated HSA, washed unbound became fragmented generated capable hydroxylating acid oxidizing cholesteryl linoleate-HSA complexes. Significant levels benzoate fragmentation occurred (10 mg/ml) containing 3.3 mol bound/mol HSA. is equivalent incubation 10 mg/ml native 0.66 mM conditions which lead formation. oxidative activity glycated dependent on transition-metal concentration. level protein-bound decrease during can oxidize generate oxidants, whether solution We discuss more likely mechanism under near-physiological used study effects exposure vitro.