An inhibitor of ornithine decarboxylase in the thymus and spleen of dexamethasone-treated rats

• Main Author: Bishop, Paul Burton
• Language: English
• Published: University of British Columbia 2010
• Online Access: http://hdl.handle.net/2429/24549

The activity of ornithine decarboxylase, the rate-determining enzyme in polyamine biosynthesis, decreases markedly in rat thymus and spleen soon after the injection of rats with dexamethasone. This study shows that as early as 2 1/2 hours after hormone treatment, when enzyme activity is very low, an inhibitor of ODC is present. Inhibition of ODC can be readily detected at 5 and 12 hours, but not at 24 hours after glucocorticoid injection. The inhibitor appears to be a protein since its activity was destroyed by heat or trypsin. It retains its activity after dialysis which differentiates it from other ODC inhibitors that require small molecular weight substances for activity. The apparent molecular weight of a partially purified extract was 54,000, which differentiates this inhibitor from antizyme, an inhibitor of ODC found in several other cell types. The inhibitor appears to act by a non-competitive and non-catalytic mechanism since the amount of inhibition does not change with time and its interaction with ODC does not affect the enzyme's affinity for ornithine. The formation of this inhibitor is an early event in lymphoid tissues in response to dexamethasone and may be important in causing the inhibition of cell division which precedes the destruction of lymphocytes. === Medicine, Faculty of === Biochemistry and Molecular Biology, Department of === Graduate