Dramatic species differences in the susceptibility of monoamine oxidase B to a group of powerful inhibitors

Matthew J. Krueger, Fathi Mazouz, Rona R. Ramsay, René Milcent, Thomas P. Singer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

Oxadiazolones and oxadiazolethiones are potent, reversible competitive inhibitors of MAO B in rat brain mitochondria. We have compared the Ki values of six of these inhibitors toward MAO B from rat, human and beef liver mitochondria, using benzylamine as substrate. Unexpectedly, their inhibitory potency varies by 3 to 4 orders of magnitude between rat and beef liver MAO B, whereas the inhibition of the rat and human liver enzymes is quite similar. Examples are 5-(4-benzyl-oxyphenyl)-3-(2-cyano-ethyl)-1,3,4- oxadiazole-2(3H)-thione, with K at 30° of 0.5 nM for rat, 0.8 nM for human, and 1,830 nM for beef liver mitochondria and 5-(4-benzyl-oxyphenyl)-3-(2-hydroxyethyl)-1,3,4- oxadiazol-2(3H)-thione, with Ki values of 1.2, 1.1 and 1,320 nM for MAO B from these three sources. Since solubilized and membrane-bound enzymes had similar sensitivities to the inhibitors, the differences seen must arise from differences in the amino acid sequences of the three enzymes.

Original languageEnglish
Pages (from-to)556-562
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume206
Issue number2
DOIs
Publication statusPublished - 1 Jan 1995

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