[show abstract][hide abstract] ABSTRACT: Semicarbazide-sensitive amine oxidase (EC 220.127.116.11) acts as a vascular-adhesion protein (VAP-1), mediating the adhesion of
lymphocytes to vascular endothelial cells under inflammatory conditions. The relationship between the adhesive and the enzymatic
functions of SSAO have not yet been fully defined. Previous studies from this laboratory showed aminohexoses, which were neither
substrates nor direct inhibitors of SSAO, bound to the enzyme as reversible inhibitors in the presence of H2O2 generated during substrate oxidation. The possibility that surface l-lysine could act similarly has been investigated in the present study. The presence of l-lysine during the oxidation of benzylamine resulted in time- and dose-dependent inhibition of SSAO activity, in a process
that was dependent on the H2O2 formed during benzylamine oxidation. The possible implications of this in terms of the therapeutic uses of lysine are discussed.
Keywords: Benzylamine, semicarbazide-sensitive amine oxidase, hydrogen peroxide (H2O2), inhibition
Journal of Neural Transmission 01/2007; 114(6):747-749. · 3.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: The effects of the drug hydroxyzine on the activities of the rat liver monoamine oxidases (EC 18.104.22.168; MAO) and the membrane-bound
and soluble forms of bovine semicarbazide-sensitive amine oxidase (EC 22.214.171.124; SSAO) were studied. Hydroxyzine was found to
be a competitive inhibitor of MAO-B (Ki ∼ 38 µM), whereas it had a low potency towards MAO-A (IC50 > 630 µM). Although it was a relatively potent competitive inhibitor of bovine plasma SSAO (Ki ∼ 1.5 µM), it was a weak inhibitor of the membrane-bound form of the enzyme from bovine lung (IC50 ∼ 1mM). These findings extend our knowledge of the drug binding capabilities of the amine oxidases and suggest that these
interactions may contribute to the complex actions of this drug.
[show abstract][hide abstract] ABSTRACT: Amine oxidase substrates such as benzylamine and methylamine have been shown to stimulate glucose uptake by increasing the
recruitment of the glucose transporter GLUT4 from vesicles within the cell to the cell surface. Inhibition of this effect
by the presence of semicarbazide and catalase led to the suggestion that the process is mediated by the H2O2 produced in the oxidation of these amines. Tyramine, which is a substrate for both MAO and SSAO, can also stimulate this
process and in that case both MAO and SSAO inhibitors attenuate the effect. Benzylamine does not occur physiologically and
tyramine is normally present in only very low amounts. We have suggested that adrenaline, which also stimulates glucose metabolism
through adrenoceptors, may act as the physiological substrate for GLUT4 recruitment. It is a substrate for MAO but not SSAO.
However, oxidation of adrenaline by MAO releases both H2O2 and methylamine for further oxidation by SSAO. In order to gain a fuller understanding of this process we have performed
simulation studies that may be used to assess the contributions of the amine oxidases to the process under a variety of conditions.
The results are consistent with the experimentally observed behaviour. This approach not only helps to establish the feasibility
of this process but also allows behaviour prediction and the identification of further experimental approaches.
Keywords: Adrenaline, glucose transport, GLUT4, hydrogen peroxide (H2O2), methylamine, monoamine oxidase, semicarbazide-sensitive amine oxidase
Journal of Neural Transmission 114(6):783-786. · 3.05 Impact Factor