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Molecular Pharmacology

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Research ArticleArticle

The Binding Order of Substrates to Phenylethanolamine N-Methyltransferase

ROBERT G. PENDLETOX and INA B. Snow
Molecular Pharmacology November 1973, 9 (6) 718-725;
ROBERT G. PENDLETOX
Research and Development Division, Smith Kline & French Laboratories, Philadelphia, Pennsylvania 19101
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INA B. Snow
Research and Development Division, Smith Kline & French Laboratories, Philadelphia, Pennsylvania 19101
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Abstract

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.

  • Copyright ©, 1973, by Academic Press, Inc.

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Molecular Pharmacology
Vol. 9, Issue 6
1 Nov 1973
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Research ArticleArticle

The Binding Order of Substrates to Phenylethanolamine N-Methyltransferase

ROBERT G. PENDLETOX and INA B. Snow
Molecular Pharmacology November 1, 1973, 9 (6) 718-725;

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Research ArticleArticle

The Binding Order of Substrates to Phenylethanolamine N-Methyltransferase

ROBERT G. PENDLETOX and INA B. Snow
Molecular Pharmacology November 1, 1973, 9 (6) 718-725;
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