Abstract
Ornithine decarboxylase (ODC), the rate-limiting enzyme in the biosynthesis of polyamines, displays high activity early in postnatal development of the heart, followed by a gradual decline to the low levels characteristic of adults. In both 2- and 4-day-old rat pups, kinetic studies revealed the presence of two distinctKmorn values of 50-60 and about 250 µM. However, by 7 days of age, only one form of the enzyme could be detected, with a Kmorn of 200-250 µM; after this point, the Kmorn remained at the low-affinity value, and further age-dependent reductions in activity occurred due to a progressive decline in the Vmax. The rate of disappearance of ODC activity, measured after the administration of cycloheximide, did not change with age. Neonatal administration of triiodothyronine (T3) evoked an initial elevation of ODC followed by depressed activity. As was true of controls, ODC from 2-day-old T3-treated rats displayed two separate kinetic forms, but the Vmax values of both forms were elevated above those of controls. At 10 days of age, only lowaffinity ODC could be found in T3-treated rats, and the Vmax was below that of controls. Cycloheximide treatment revealed only small changes in the half-life of ODC activity after T3 treatment. The accelerated maturational decline of cardiac ODC in hyperthyroid rats was correlated with depressed RNA synthesis and with subsequent deficits in heart weight. These results indicate that the developmental decline of heart ODC can be explained by the disappearance of the high-affinity kinetic form of the enzyme as well as by a reduction in enzyme synthesis and/or catalytic efficiency; after its initial stimulatory effect, neonatal hyperthyroidism exerts a deleterious effect on ODC activity which may contribute to deficient nucleic acid synthesis and cardiac growth.
- Copyright © 1980 by The American Society for Pharmacology and Experimental Therapeutics
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