Comparison of the inactivation of microsomal glucose-6-phosphatase by in situ lipid peroxidation-derived 4-hydroxynonenal and exogenous 4-hydroxynonenal.
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.
Koster
J F
JF
Department of Biochemistry I, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
Slee
R G
RG
Montfoort
A
A
Lang
J
J
Esterbauer
H
H
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008862:Microsomes, Liver; D051381:Rats
D000447:Aldehydes; D005952:Glucose-6-Phosphatase; C027576:4-hydroxy-2-nonenal