Molecular Pharmacology, Vol 14, 490-501, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Regulation of Phenylethanolamine N-Methyltransferase Synthesis and Degradation

II. Control of the Thermal Stability of the Enzyme by an Endogenous Stabilizing Factor

¹ Child Psychiatry Program, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305

The levels of rat adrenal phenylethanolamine N-methyltransferase fall dramatically following hypophysectomy and can be restored to normal values by the administration of adrenocorticotrophin or glucocorticoids. Studies using combined radiolabeling and immunochemical techniques reveal that hypophysectomy accelerates degradation of the enzyme and that proteolysis of the enzyme in vivo is under regulation by glucocorticoids. After hypophysectomy the stability of phenylethanolamine N-methyltransferase at 50° is profoundly reduced, suggesting that concomitant with the increased susceptibility of the enzyme to proteolysis in vivo is an enhanced vulnerability to thermal denaturation in vitro. The thermal stability of the enzyme seems to be regulated by a freezing-thawinglabile, dialyzable substance present in the adrenal glands of normal rats. This material, termed stabilizing factor, is lost after hypophysectomy and can be restored by the administration of ACTH or dexamethasone. The stabilizing factor appears to act by binding to phenylethanolamine N-methyltransferase and can be dissociated from the immunoadsorbed enzyme by washing. The partially purified stabilizing factor has an absorption maximum at 264 nm; preliminary results indicate that it may be S-adenosylmethionine. Thus it is possible that binding of the enzyme to S-adenosylmethionine confers stability against proteolysis in vivo and thermal denaturation in vitro.