Stimulation of rat heart ornithine decarboxylase by isoproterenol evidence for post-translational control of enzyme activity?
The activity of rat heart ornithine decarboxylase (ODC), the enzyme involved in the initial step of polyamine biosynthesis, was markedly stimulated after isoproterenol treatment, reaching a maximum of about four times the basal value four hours after administration. At all times after isoproterenol, kinetic studies revealed only two forms of the enzyme with Km values for ornithine of 35-50 microM and 190 microM, compared to only one form (190 microM) in the controls. At no time was a form of ODC with an intermediate Kornm detected, nor did dialysis reverse stimulation of activity of enzyme from isoproterenol-treated rats, or increase activity in control preparations; it is therefore unlikely that small molecular activators or inhibitors participate in the stimulation. The time course of Vmax values for the high-affinity component of the enzyme coincided with that of net enzyme activity, indicating that increases of ODC activity in response to isoproterenol might result from a shift of enzyme from its low-affinity state to the high-affinity form, rather than from appearance of additional enzyme molecules. In support of this hypothesis, alpha-difluoromethylornithine, an irreversible ODC inhibitor, displayed identical ID50 values in control and isoproterenol-treated animals, a situation which would not occur if more enzyme were present. These data are consistent with the view that post-translational control mechanisms involving macromolecular factors could operate in regulating cardiac ODC activity.
D000818:Animals; D002262:Carboxy-Lyases / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D007545:Isoproterenol