Molecular Pharmacology, Vol 2, 106-116, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

The Effects of Adrenalectomy and Hydrocortisone on Rat Liver Metabolites and Glycogen Synthetase Activity

¹ Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri

An attempt has been made to locate the defect in glycogen synthesis which results from adrenalectomy and to find the mechanism by which hydrocortisone corrects this defect. The levels of 12 metabolites believed to be associated with the pathway from lactate to glycogen were studied, and the results indicate that the major defect following adrenalectomy occurs at the step between UDP-glucose and glycogen. This was confirmed by attempts to induce glycogen formation with lactate administration. When glycogenesis was restored with hydrocortisone the changes in metabolite levels indicated that the UDP-glucose to glycogen step was greatly facilitated.

In vitro measurements of hepatic glycogen synthetase activities, together with kinetic studies of the enzyme, showed that adrenalectomy does not lower the total synthetase level, but causes a conversion of most of the enzyme to the form that is dependent on glucose-6-P for activity. Hydrocortisone, conversely, does not significantly change the total synthetase level but converts a substantial amount of the glucose-6-P dependent synthetase to the "independent" form. It is concluded that glucocorticoids permit glycogen synthesis by maintaining part of the glycogen synthetase in the form which is active even at low glucose-6-P levels.

Note:
ACKNOWLEDGMENT This study was supported by NSF Grant G-18959 and USPHS Grants HD-00376 and NB-01352.

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