Inhibition and inactivation of monoamine oxidase by 3-amino-1-phenyl-prop-1-enes.
We have previously shown that E-3-amino-1-phenyl-prop-1-ene (E-cinnamylamine) is readily oxidised by monoamine oxidase (MAO) type B from either rat or bovine liver (Williams et al. (1988), Biochem. J. 256, 411-415) in each case producing a non-linear progress curve which was attributed to inhibition by the reaction product E-cinnamaldehyde. We have now found that although this aldehyde inhibits MAO B competitively (Ki 0.017 mM) this cannot account for the inhibitory process, since during a 60 min incubation with the substrate (0.5 mM; Km, 0.074 mM) more than 95% inhibition of MAO B was observed and the concentration of aldehyde had reached approx. 0.025 mM. Inhibition was relieved either by dialysis or dilution of inhibited samples. The activity of MAO A from rat liver was largely unaffected by E-cinnamylamine. Oxidation of N-methyl-E-cinnamylamine and its Z-isomer by MAO B produced progress curves similar to that obtained with the primary amine, but in these cases inhibition was not reversed either by dilution or dialysis. Partition ratios for the pair of N-methyl isomers with bovine MAO B were calculated to be 1640 (E-isomer) and 1430 (Z-isomer). The time-dependent inhibition process for all three amines obeyed pseudo-first-order kinetics. A tritiated form of N-methyl-E-cinnamylamine, incubated with MAO B from bovine liver, resulted in incorporation of radioactivity into the enzyme. This labelling was stable to dialysis and to SDS-PAGE.
Williams
C H
CH
Division of Biochemistry, School of Biology and Biochemistry, Medical Biology Centre, Queen's University, Belfast, U.K.
Lawson
J
J
Backwell
F R
FR
D000171:Acrolein / Q000031:analogs & derivatives / Q000032:analysis; D000818:Animals; D001547:Benzaldehydes / Q000032:analysis; D001596:Benzylamines / Q000494:pharmacology; D001665:Binding Sites; D002417:Cattle; D008099:Liver / Q000201:enzymology; D008744:Methylamines / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism
D001547:Benzaldehydes; D001596:Benzylamines; D008744:Methylamines; D008996:Monoamine Oxidase Inhibitors; D011437:Propylamines; C058556:cinnamylamine; C073280:N-methylcinnamylamine; D000171:Acrolein; C030796:benzylamine; D008995:Monoamine Oxidase; C012843:cinnamaldehyde; C032175:benzaldehyde