Rates of recovery of irreversibly inhibited monoamine oxidases: A measure of enzyme protein turnover

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Summary

  1. After irreversible inhibition of monoamine oxidase (MAO) in rats with hydrazine derivatives (3-amino-2-oxazolidinone, furazolidone, benmoxine) and the non-hydrazine pargyline, recovery of enzyme activity occurred at rates which were characteristic for the organ investigated and independent of the chemical structure of the irreversible inhibitor. The respective half times were the same in homogenates and in mitochondria and amounted to about 10 days in the brain and 3 to 4 days in the liver; in the small intestine, mucosal MAO activity recovered with a half time of 0.5 days, whereas in the residual intestinal layers a half time of about 4 days was found.\3-Tranylcypromine is not an irreversible inhibitor: the half times of MAO recovery were 3.6 days in the brain and 2.4 days in the liver.

    Thus, long duration of inhibition and organ-specific half times of recovery of MAO inhibition are characteristic features of irreversible inhibitors.

  2. When mitochondrial protein was labelled by i.v. injection of 14C-leucine, specific radioactivity declined with a half time of 9.4 days in the brain and 4.0 days in the liver; for the intestinal mucosa and for the residual intestinal layers, a half time of 0.5 and 4.4 days, respectively, was found.

    As these values are nearly identical with those found for the rates of MAO recofery after irreversible inhibition, the assumption is supported that irreversibly inhibited MAO must be replaced by newly synthetized enzyme. Vice versa, the rates of MAO recovery after irreversible inhibition seem to reflect the rates of mitochondrial protein turnover. Measurements of the rate of recovery of irreversibly inhibited MAO activity may therefore be useful to determine the turnover of the enzyme protein.

Part of this work was presented to the 11. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft, Mainz 1970 (Planz et al., 1970).
This work was supported by a grant from the Deutsche Forschungsgemeinschaft.