Effects of glyceraldehyde on the structural and functional properties of sickle erythrocytes

The d- and l-isomers of glyceraldehyde are equally effective in the inhibition of SS erythrocyte sickling in vitro. The following compounds at a concentration of 20 mM were ineffective in inhibiting sickling: glyceraldehyde-3-phosphate, d-erythrose, d-ribose, d-fructose, d-glucose, d-sucrose, dihydroxyacetone, and methylglyoxal. Glyceraldehyde does not reverse the sickling of cells in the deoxy state. The properties of purified hemoglobin after treatment with glyceraldehyde and of the hemoglobin isolated from treated cells are very similar; these results suggest that glyceraldehyde itself is the reactive species within the erythrocyte. Erythrocyte glutathione is decreased by treatment in vitro with the aldehyde. Relatively high concentrations of glyceraldehyde (50 mM) lead to a small amount (3%) of cross-linking between hemoglobin monomers as well as to some cross-linking of erythrocyte membrane proteins. Lower concentrations of dl-glyceraldehyde (5-20 mM), which reduce the sickling of erythrocytes in vitro, lead to proportionally less cross-linking of hemoglobin. Cells that have been treated with those concentrations of the aldehyde show little change in their osmotic fragility, exhibit improved filtration properties, and have a lowered viscosity.