4-HYDROXY-2-NONENAL HARDLY AFFECTS GLYCOLYSIS

4-Hydroxy-2-nonenal (HNE), one of the major products of lipid peroxida tion, inactivated the rate-limiting enzymes (from animal sources) of t he glycolytic pathway and the pentose phosphate pathway when incubated at 37 degrees C for 1 h in the absence of glutathione (GSW). The HNE concentration for half-maximal inactivation of 6-phosphofructokinase ( PFK) and glyceraldehyde-3-phosphate hydrogenase was 3-10 mu M; and tha t Value for pyruvate kinase, glucose-6-phosphate dehydrogenase, and he xokinases I and II was 0.15-0.6 nM. In the presence of 5 mM GSH, howev er, only PFK, irrespective of the source (muscle, liver. or erythrocyt e). was inactivated by 40-50% when incubated with 0.1 mM WNE for 1 h. Even PFK was not inactivated in the presence of both GSH and its subst rate, ATP (2 mM). Glycolysis in human erythrocytes was not affected by treatment of cells with 0.1 mM HNE at 37 degrees C for 30 min. The re sults suggest that HNE, at concentrations observable under physiologic al and pathological conditions, hardly affects glycolysis in cells. (C ) 1997 Elsevier Science Inc.