Effects of lipid peroxidation on membrane-bound enzymes of the endoplasmic reticulum.
1. Induction of the formation of lipid peroxide in suspensions of liver microsomal preparations by incubation with ascorbate or NADPH, or by treatment with ionizing radiation, leads to a marked decrease of the activity of glucose 6-phosphatase. 2. The effect of peroxidation can be imitated by treating microsomal suspensions with detergents such as deoxycholate or with phospholipases. 3. The substrate, glucose 6-phosphate, protects the glucose 6-phosphatase activity of microsomal preparations against peroxidation or detergents. 4. The loss of glucose 6-phosphatase activity is not due to the formation of hydroperoxide or formation of malonaldehyde or other breakdown products of peroxidation, all of which are not toxic to the enzyme. 5. All experiments lead to the conclusion that the loss of activity of glucose 6-phosphatase resulting from peroxidation is a consequence of loss of membrane structure essential for the activity of the enzyme. 6. In addition to glucose 6-phosphatase, oxidative demethylation of aminopyrine or p-chloro-N-methylaniline, hydroxylation of aniline, NADPH oxidation and menadione-dependent NADPH oxidation are also strongly inhibited by peroxidation. However, another group of enzymes separated with the microsomal fraction, including NAD(+)/NADP(+) glycohydrolase, adenosine triphosphatase, esterase and NADH-cytochrome c reductase are not inactivated by peroxidation. This group is not readily inactivated by treatment with detergents. 7. Lipid peroxidation, by controlling membrane integrity, may exert a regulating effect on the oxidative metabolism and carbohydrate metabolism of the endoplasmic reticulum in vivo.
D000632:Aminopyrine / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008566:Membranes / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009249:NADP / Q000378:metabolism / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism*; D010740:Phospholipases / Q000494:pharmacology; D011830:Radiation Effects; D051381:Rats; D014812:Vitamin K / Q000378:metabolism
D000814:Aniline Compounds; D001647:Bile Acids and Salts; D010545:Peroxides; D000632:Aminopyrine; D014812:Vitamin K; D009249:NADP; D010088:Oxidoreductases; D010740:Phospholipases; D005952:Glucose-6-Phosphatase; D009699:N-Glycosyl Hydrolases; D001205:Ascorbic Acid