Studies on the mechanisms of ornithine decarboxylase in vitro inactivation.
Hydrocortisone-induced rat liver ornithine decarboxylase appears quite stable in the soluble fraction of the homogenate incubated at 37 degrees C. In contrast, the incubation of the whole homogenate causes a rapid loss of activity. The ornithine decarboxylase-inactivating capacity appears mainly bound to microsomes. Lysosomes seem to play a role only after the microsome-induced inactivation. Different reducing agents (dithiothreitol, NADPH, NADH, GSH) are effective both in preventing and in reversing ornithine decarboxylase inactivation. NADPH is peculiar in that it can reactivate the enzyme at very low concentrations. Oxidized glutathione potentiates the inactivating effect of microsomes. On the basis of present results it is suggested that ornithine decarboxylase may be reversibly inactivated through microsome-catalyzed formation of mixed or enzyme-enzyme disulfides and that NADPH plays a crucial role in ornithine decarboxylase reactivation, probably by cytosolic reductase(s).
D000375:Aging; D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D003600:Cytosol / Q000201:enzymology; D004790:Enzyme Induction; D006854:Hydrocortisone / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000235:genetics; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology
D065108:Ornithine Decarboxylase Inhibitors; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D006854:Hydrocortisone