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by Irwin B. Levitan
| Institution: | McGill University |
|---|---|
| Department: | Department of Biochemistry. |
| Degree: | PhD |
| Year: | 1971 |
| Keywords: | Biochemistry. |
| Posted: | |
| Record ID: | 1560757 |
| Full text PDF: | http://digitool.library.mcgill.ca/thesisfile129142.pdf |
The analogs 8-azaguanine and 5-azacytidine do not inhibit the initial steroid-mediated induction of tyrosine transaminase; however, the continued induced synthesis of the enzyme, elicited by repeated doses of hydrocortisone, is inhibited in the presence of the analogs after approximately 6 hours. It is inferred from these and other data that the induction cycle involves the activation by hydrocortisone, and subsequent turnover, of a pool of preexisting inactive messenger RNA for tyrosine transaminase. This study provides the first functional test for the existence of such pools. 8-Azaguanine, 5-azacytidine and cycloheximide can maintain the tyrosine transaminase activity at or near the induced level for a prolonged period following induction of the enzyme by hydrocortisone. Immunochemical experiments confirm that this maintenance phenomenon results from an inhibition of tyrosine transaminase degradation. This in turn may be due to the inhibition of the synthesis of a degradative enzyme.
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