RT Journal Article SR Electronic T1 The Binding Order of Substrates to Phenylethanolamine N-Methyltransferase JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 718 OP 725 VO 9 IS 6 A1 ROBERT G. PENDLETOX A1 INA B. Snow YR 1973 UL http://molpharm.aspetjournals.org/content/9/6/718.abstract AB We have studied the substrate binding order of S-adenosylmethionine and norepinephrine to phenylethanolamine N-methyltransferase via the use of two inhibitors of this enzyme. 2-(2,5-Dichlorophenyl)cyclopropylamine hydrochloride (SK&F 9208) competitively inhibited norepinephrine as the variable substrate but was an uncompetitive inhibitor with respect to S-adenosylmethionine. S-Adenosylhomocysteine, however, was a competitive inhibitor with respect to S-adenosylmethionine but noncompetitive as an antagonist of norepinephrine. These studies are interpreted to suggest a kinetically ordered pattern of substrate binding to the enzyme, with S-adenosylmethionine being initially bound. ACKNOWLEDGMENTS The authors wish to thank Mr. George Gessner, Miss Deborah Seltz, and Miss Julie Wang for their excellent technical assistance in carrying out this project. A special note of thanks is also due Dr. Harry Green for his helpful encouragement of our efforts.