Key points are not available for this paper at this time.
The incubation of dialyzed hemoglobin A with a number of phosphorylated glycolytic intermediates leads to the formation of covalent hemoglobin adducts that co-chromatograph with hemoglobin AIb. Phosphorylated hexoses (glucose-6-P, fructose-6-P, fructose-1,6-P2) and trioses (glyceraldelyde-3-P, dihydroxyacetone-P) containing a free aldehyde or ketone can glycosylate hemoglobin A nonenzymatically. From 7 to 12% of the hemoglobin can be modified after a 72-h incubation of an equimolar mixture of hemoglobin A and the phosphorylated intermediate. No significant formation of adduct was seen with a sugar alone (glucose, fructose) or glycolytic intermediate which had a blocked aldehyde (glucose-1-P, glucose-1,6-P2, UDP-glucose). The addition of an equimolar amount of 2,3-diphosphoglycerate reduced adduct formation. Evidently, the phosphate is needed to orient and stabilize the intermediate in the bisphosphoglycerate pocket of hemoglobin so that the addition reaction can proceed. All of the hemoglobin A adducts were indistinguishable form hemoglobin AIb by ion exchange chromatography and isoelectric focusing. The hemoglobin A-glucose-6-P adduct and hemoglobin AIb had a NaB3H4-reducible linkage in the beta chain. The concentration of hemoglobin AIb is elevated in patients with diabetes mellitus. This presumably reflects the increased concentrations of glycolytic intermediates (glucose-6-P, fructose-6-P, fructose-1,6-P2, dihydroxyacetone-P) which were found to be significantly elevated in the red cells of diabetic patients as compared with normal controls.
Stevens et al. (1977) studied this question.