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Molecular Pharmacology, Vol 2, 526-533, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

The Mechanism of the Inhibition of Aminotransferases by Salicylate

B. J. GOULD 1, P. D. DAWKINS 1, M. J. H. SMITH 1, and A. J. LAWRENCE 1

1 Arthritis and Rheumatism Research Unit, King’s College Hospital Medical School, Denmark Hill, London, and the Pharmacology Department, University college, London, England

Salicylate inhibits pig heart alanine and aspartate aminotransferase activities in vitro. The inhibitions are reversible, involving competition with agr-oxoglutarate and alanine for the alanine aminotransferase and with agr-oxoglutarate and aspartate for the aspartate aminotransferase. The results are consistent with a binary mechanism for the action of the aminotransferases. In addition they show that salicylate inhibits alanine aminotransferase much more strongly than aspartate aminotransferase. These results are discussed with reference to some of the in vivo actions of the drug.

Note:
ACKNOWLEDGMENT We wish to thank the Arthritis and Rheumatism Research Council for generous financial support and the Nuffield Foundation for a grant towards the purchase of the spectrophotometer used in the work.

Submitted on July 1, 1966






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