title: Dramatic species differences in the susceptibility of monoamine oxidase B to a group of powerful inhibitors.
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 towards 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)-th ione, with Ki at 30 degrees of 0.5 nM for rat, 0.8 nM for human, and 1,830 nM for beef liver mitochondria and 5-(4-benzyloxyphenyl)-3-(2-hydroxyethyl)-1,3,4-oxadiazol-2(3 H)-one 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.
authors: Department of Biochemistry and Biophysics, University of California at San Francisco 94143.
authors: M J
authors: MJ
authors: Krueger
authors: F
authors: F
authors: Mazouz
authors: R R
authors: RR
authors: Ramsay
authors: R
authors: R
authors: Milcent
authors: T P
authors: TP
authors: Singer
mesh_terms: D000818:Animals; D002417:Cattle; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000201:enzymology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase