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Journal of Pharmacology And Experimental Therapeutics, Vol. 134, Issue 1, 77-82, 1961
Copyright © 1961 by American Society for Pharmacology and Experimental Therapeutics


STUDIES ON THE MECHANISM OF INHIBITION OF LIVER AND ERYTHROCYTE CATALASE ACTIVITY BY 3-AMINO-1,2,4-TRIAZOLE (AT)

T. R. Tephly 1, G. J. Mannering 1, and R. E. Parks Jr. 1

1 Department of Pharmacology and Toxicology, The University of Wisconsin, Madison, Wisconsin

Results on the mechanism of inactivation of liver and erythrocyte catalase activity by 3-amino-1,2,4-triazole (AT) have been presented. Hydrogen peroxide generated enzymatically, as for example by the hypoxanthine-xanthine oxidase reaction, has been shown to be necessary for the inhibition of catalase activity by AT. It is postulated from both in vivo and in vitro studies that methanol and ethanol, alcohols known to react with catalase-hydrogen peroxide complex I, compete with AT, and thereby prevent inactivation of catalase by AT.

The failure of AT to inhibit erythrocyte catalase, while greatly inhibiting liver catalase, is explained on the basis that these cells are normally unable to generate sufficient hydrogen peroxide. When erythrocytes are exposed to both AT and methylene blue, catalase activity is rapidly depressed. It is suggested that methylene blue induces the production of hydrogen peroxide necessary for AT activity.

Submitted on March 22, 1961




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