The monosaccharides, glucose, fructose and galactose can interact with serum and/or cellular proteins resulting in nonenzymatic glycation related to pathophysiology in diabetes mellitus and normal aging.  The most studied of these processes involves the interaction of glucose with erythrocytic human hemoglobin A (HbA).  The prevailing assumption is that a ring-opened glucose isomer is the singular reactive structure that leads to the formation of a Schiff base and, ultimately, to glycated HbA.  Based upon computational assessment utilizing protein/substrate docking protocols, the ring-closed a- and �-pyranoses preferentially bind to HbA followed by ring opening while bound.  To assess the generality of this mechanistic chemistry, the binding of the five fructose isomers to a single �-chain of HbA was investigated.  Non-isomer specific binding that proceeds with low amino acid residue selectivity was observed.  Similar to HbA, human serum albumin (HSA) can undergo glycation by circulating glucose at a variety of amino acid residues.  Each of the monosaccharides tested bind more exothermically to HSA than to HbA.  Also consistent with HbA, binding of glucose and fructose isomers to HSA occurs with low isomer specificity and low amino acid residue selectivity and involves initial binding of the ring-closed isomer. Similar binding trends are observed for galactose and xylulose isomers, supporting the generality of the initial noncovalent binding of monosaccharides to proteins as being energetically favored, transient, reversible events proceeding with low isomer specificity and low amino acid residue selectivity primarily involving ring-closed species that, if they are to proceed in the glycation process, must ring open while bound.  The results from the kinetics of experimental monosaccharide binding to HbA to HSA under controlled incubations are compared to assess relative glycation rates, and together with the computational results, are discussed in terms of potential implications on the clinical measure referred to as the glycation gap.

Comparison of the initial noncovalent binding of D-glucose and D-fructose with hemoglobin and albumin in nonenzymatic glycation

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.