Effect of malondialdehyde, a product of lipid peroxidation, on the function and stability of hemoglobin.

Malondialdehyde (MDA) was found to react with normal hemoglobin A (Hb A), forming a number of less cationic components which were detected by cellulose acetate electrophoresis and gel electrofocusing. All the modified components moved down the cation-exchange resin at a quicker rate than Hb A, and this chromatographic behavior of the modified components was similar to that of glycosylated Hb A. Some of these modified components were intermolecularly crosslinked, and showed fluorescence with an excitation maximum at 390 nm and an emission maximum at 460 nm. It is likely that MDA reacts nonspecifically with the epsilon-amino groups of lysine and N-terminal amino groups to produce aminoacrolein, crosslinks, and strongly fluorescent 1,4-dihydropyridine-3,5-dicarbaldehyde. Oxygen affinity of the modified hemoglobins was increased. The modified hemoglobins were more readily oxidized into met-form. Mechanical stability of Hb A was also decreased by the modification. These results suggest that a considerable conformational change in Hb A was induced by the treatment with MDA. Since MDA is generated in erythrocytes as a consequence of liquid peroxidation, MDA may react with intracellular Hb A and influence the function and the stability of hemoglobin.