Molecular Pharmacology, Vol 7, 219-228, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

The Labeling in Vivo of Monoamine Oxidase by ¹⁴C-Pargyline: a Tool for Studying the Synthesis of the Enzyme

¹ School of Pharmacy, University of Colorado, Boulder, Colorado 80302, and Department of Pharmacology, University of Colorado School of Medicine, Denver, Colorado 80220

Pargyline (N-methyl-N-2-propynylbenzylamine), an irreversible inhibitor of monoamine oxidase in vitro, was found to bind irreversibly to the enzyme in vivo. The apparent covalent nature of the latter binding was established by exhaustive washing and treatment of the protein with trichloracetic acid. The inhibitor was selective for monoamine oxidase in vivo as well as in vitro, which permitted the determination of the turnover rates of monoaminse oxidase in various subcellular fractions of rat liver. The half-life of mitochondrial monoamine oxidase was approximately 3.5 days, as determined by the rate of recovery of enzyme activity or by the decay of radioactivity after administration of sufficient 7-¹⁴C-pargyline to inhibit the enzyme completely. Similarly, the half-life of microsomal monoamine oxidase was found to be approximately 1 day. Evidence is presented suggesting that radioactively labeled, inactive monoaminse oxidase may be taken up by lysosomes. Cycloheximide completely prevented the recovery of monoamine oxidase activity in the microsomal fractions and markedly inhibited the rate of recovery of enzyme activity in the mitochondrial fractions.