Molecular Pharmacology, Vol 3, 497-502, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics

Studies with Specific Enzyme Inhibitors

XI. Identification of Tissue-Specific Metabolic Organization of Mitochondria by Monofluorocitrate

¹ Departments of Pharmacology and Biochemistry and the Cardiovascular Research Institute, University of California, School of Medicine, San Francisco, California 94122

Rates of O₂ uptake of mitochondria vary depending on the nature of added substrate, on assay conditions, and on the tissue from which mitochondria are isolated. Inhibition of aconitase by fluorocitrate influenced O₂ uptake and citrate accumulation in a highly selective manner. Metabolic effectivity of fluorocitrate was dependent on the same variables which determine specific metabolic rates in the absence of the inhibitor. It is proposed that the experimental design applied detects metabolic consequences of tissue-specific control mechanisms.

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ACKNOWLEDGMENTS The work reported in this paper was supported by research grants of the U.S. Public Health Service (RO1-HD-01239-11 and RO1-CA-07955-03), the National Science Foundation (GB-5749), and the American Heart Association, Inc. (66-652).