Comparison of the Inactivation of Microsomal Glucose-6-Phosphatase by in Situ Lipid Peroxidation-Derived 4-Hydroxynonenal and Exogenous 4-Hydroxynonenal

Abstract

1) The effect of 4-hydroxynonenal and lipid peroxidation on the activities of glucose-6-phosphatase and palmitoyl CoA hydrolase were studied. 2) 4-Hydroxynonenal inactivates glucose-6-phosphatase but has no effect on palmitoyl-CoA hydrolase. These effects are similar with those observed during lipid peroxidation of microsomes. 3) The inhibition of glucose-6-phosphatase by 4-hydroxynonenal can be prevented by glutathione but not by vitamin E. The inactivation of glucose-6-phosphatase during lipid peroxidation is prevented by glutathione and delayed by vitamin E. 4) The formation of 4-hydroxynonenal during lipid peroxidation was followed in relation to the inactivation of glucose-6-phosphatase. At 50% inactivation of glucose-6-phosphatase the 4-hydroxynonenal concentration was 1.5 microM. To obtain 50% inactivation of glucose-6-phosphatase by added 4-hydroxynonenal a concentration of 150 microM or 300 microM was needed with a preincubation time of 30 and 60 min, respectively. 5) It is concluded that the glucose-6-phosphatase inactivation during lipid peroxidation can be due to the formation of 4-hydroxynonenal. The formed 4-hydroxynonenal which inactivates glucose-6-phosphatase is located in the membrane. If this mechanism is valid it implies that a functional SH group of glucose-6-phosphatase is layered in the membrane. However, an inactivation of glucose-6-phosphatase by desintegration of the membrane by lipid peroxidation cannot be ruled out.

Catabolism of 4-Hydroxyacids and 4-Hydroxynonenal via 4-Hydroxy-4-phosphoacyl-CoAs

“…4-Hydroxynonanoate and related compounds are derived from the lipid peroxidation product 4-hydroxynonenal (1), the concentration of which in microsomal membranes can reach mM levels during bursts of lipid peroxidation (43). Although mM concentrations of 4-hydroxynonenal, as used in our study, can have cytotoxic effects (11), our study concentrated on the degradative pathways of the 4-hydroxynonenal carbon skeleton.…”

4‐Hydroxynonenal in the Pathomechanisms of Oxidative Stress

“…In general terms, the biological occurrence of the hydroxyalkenal appears within the range of 0.1-1 ¹M (5). Under de ned pathological processes, HNE steady-state concentration within membranes can easily reach 5-10 ¹M (18) or more (19), despite an active cellular metabolism, because of its high lipid/water compartmentalization coef cient (5).…”

Contribution of Lipid Dynamics on the Inhibition of Bovine Brain Synaptosomal Na+-K+-ATPase Activity Induced by 4-Hydroxy-2-nonenal

“…3,6) Koster et al also reported that the concentration of HNE in the lipid bilayer of peroxidized microsomes is about 4.5 mM. 7) HNE directly interacts with several amino acid residues of protein, i.e., the sulfhydryl (SH) group of cysteine, the imidazole moiety of histidine and the e-amino group of lysine through a Michael-type nucleophilic addition.…”