SYNTHESIS OF ISOORNITHINES AND METHYLPUTRESCINES - AN EVALUATION OF THEIR INHIBITORY EFFECTS ON ORNITHINE DECARBOXYLASE

2-(Aminomethyl)-4-aminobutyric acid (isoornithine), 3-methylisoornithi ne, and 2,3-dimethylisoornithine were not decarboxylated by liver orni thine decarboxylase (ODC, EC 4.1.1.17) of thioacetamide-treated rats b ut were good competitive inhibitors of the enzyme (Ki ranged from 0.72 to 1.79 mM). When assayed in vivo in the treated rats, the above ment ioned isoornithines were also found to inhibit liver ODC when administ ered 1 h before sacrifice. When the methylputrescines formally derived from the decarboxylation of several isoornithines were assayed on rat liver ODC, it was found that only 2,3-dimethylputrescine decreased th e enzymatic activity. When assayed in vivo, it was found to decrease O DC activity by 60%, when the latter was measured Ih after administrati on. The effect was reverted 4 h after administration of the drug. Isoo rnithines were not taken up by H-35 hepatoma cells; hence they did not affect their ODC activity. 2,3-Dimethylputrescine however, was transp orted into the cells and significantly decreased its ODC activity.