Molecular Pharmacology, Vol 7, 122-128, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

Mitochondrial Protein Synthesis: Inhibition by Emetine Hydrochloride

¹ Department of Pediatrics and Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Emetine hydrochloride has previously been described as an inhibitor of ribosomal protein synthesis in eukaryotic cells but not in bacteria [A. P. Grollman, Proc. Nat. Acad. Sci. U. S. A. 56, 1867 (1966)]. I wish to report that this ipecac alkaloid inhibits protein synthesis in mitochondrial systems derived from mouse liver. Structural relatives of emetine, such as isoemetine hydrobromide and O-methylpsychotrine oxylate, which are relatively ineffective as inhibitors of ribosomal protein synthesis, also inhibit mitochondrial protein synthesis but at concentrations that are about an order of magnitude greater than those required for inhibition by emetine hydrochloride. Anisomycin, which also inhibits ribosomal protein synthesis in eukaryotic cells but not in bacteria, fails to inhibit mitochondrial protein synthesis. These findings reveal new structural and conformational subtleties with respect to the susceptibility of various protein-synthesizing systems to ipecac alkaloids and their conformational analogues, the glutarimide antibiotics.

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ACKNOWLEDGMENT Excellent technical assistance was provided by Mrs. Elizabeth Moen.