Posttranslational modification of ornithine decarboxylase by its product putrescine

Putrescine, spermidine, and spermine, as well as other primary amine substances, when added exogenously to growth-stimulated systems, inhibit ornithine decarboxylase (ODC) activity in a dose- and time-dependent manner. Evidence is presented to support a direct posttranslational modification of ODC by transglutaminase-mediated putrescine incorporation. Purified ODC serves as an acceptor protein for putrescine in the presence of transglutaminase purified from guinea pig liver. The transamidation of putrescine to ODC results in a linear decrease in activity. The Km for putrescine is 0.4 mM and the Ki for putrescine inhibition of ODC activity by transglutaminase is 0.4 mM. The kinetics are identical to those reported for physiological systems. In regenerating rat liver, protein conjugated putrescine parallels increased transglutaminase activity and the rapid disappearance of ODC activity at 8 h. These data strongly suggest that posttranslational modification of ODC by putrescine may be an important regulatory step in the trophic cascade.