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Molecular Pharmacology, Vol 20, 159-164, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Conversion of Catalase to the Secondary Catalase-Peroxide Complex (Compound II) by agr-Methyldopa

DEAN P. JONES 1, DAVID B. MEYER 1, BO ANDERSSON 1, and STEN ORRENIUS 1

1 Department of Biochemistry, Emory University, Atlanta, Georgia 30322, and Department of Forensic Medicine, Karolinska Institute, Stockholm, Sweden

agr-Methyldopa stimulates the conversion of the primary catalase-peroxide complex (Compound I) to the catalytically inactive secondary catalase-peroxide complex (Compound II) in solutions of purified catalase as well as in suspensions of isolated hepatocytes. The rate of Compound II formation is dependent upon both the rate of H2O2 generation and the concentration of agr-methyldopa. The catalase-dependent oxidation of agr-methyldopa to the corresponding dihydroxyindole nucleus occurs much more rapidly than the formation of Compound II and suggests that the catalase-dependent one-electron oxidation of agr-methyldopa may initiate a free radical process. These reactions may be important in agr-methyldopa-induced hepatotoxicity.

Submitted on September 2, 1980
Accepted on March 20, 1981






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