J. O’Sullivan

Publications (4)8.19 Total impact

• Article: Hydrogen peroxide derived from amine oxidation mediates the interaction between aminosugars and semicarbazide-sensitive amine oxidase

  J. O’Sullivan, G. Davey, M. O’Sullivan, K. F. Tipton
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  ABSTRACT: Semicarbazide-sensitive amine oxidase (SSAO) also functions as a vascular-adhesion protein (VAP-1). The nature of the target site on lymphocytes to which endothelial-cell SSAO/VAP-1 binds is unknown. We have shown that amino sugars (galactosamine, glucosamine and mannosamine), which are not SSAO substrates, can bind to the enzyme as reversible inhibitors. Thus, they serve as a model system in which to study the interaction process. Binding occurred during substrate (benzylamine) oxidation but not when the amino sugar was incubated, for extended periods, with SSAO alone. These results suggest that one, or more of the products of the SSAO-catalysed amine oxidation might be necessary for the inhibitory process to occur. Two of the reaction products of benzylamine oxidation, benzaldehyde and ammonia were found to have no effect on the inhibition of SSAO by galactosamine. Preincubation of the enzyme with galactosamine plus H2O2 was, however, found to result in time-dependent inhibition. This is not a result of the non-enzymic reaction between H2O2 and the amino sugar, since preincubation of galactosamine with H2O2 alone, for extended periods, did not give rise to an inhibitory species. The amount of exogenously added H2O2 necessary for inhibition was very much greater than that formed during substrate oxidation. These results suggest that the H2O2 formed as a product of the SSAO-catalysed oxidation reaction is more efective in promoting the binding of amino sugars. Keywords: Galactosamine, SSAO (semicarbazide-sensitive amine oxidase), VAP-1 (vascular-adhesion protein 1), benzylamine
  Acta Neurovegetativa 04/2012; 114(6):751-756. · 2.73 Impact Factor
• Source

  Available from: Aldo Olivieri

  Article: l-lysine as a recognition molecule for the VAP-1 function of SSAO

  A. Olivieri, K. Tipton, J. O’Sullivan
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  ABSTRACT: Semicarbazide-sensitive amine oxidase (EC 1.4.3.6) 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
  Acta Neurovegetativa 04/2012; 114(6):747-749. · 2.73 Impact Factor
• Article: Modelling the roles of MAO and SSAO in glucose transport

  A. McDonald, K. Tipton, J. O’Sullivan, A. Olivieri, G. Davey, A.-M. Coonan, W. Fu
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  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
  Acta Neurovegetativa 04/2012; 114(6):783-786. · 2.73 Impact Factor
• Chapter: Inhibition of amine oxidases by the histamine-1 receptor antagonist hydroxyzine

  J. O’Sullivan, M. I. O’Sullivan, K. F. Tipton, G. Davey
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  ABSTRACT: The effects of the drug hydroxyzine on the activities of the rat liver monoamine oxidases (EC 1.4.3.6; MAO) and the membrane-bound and soluble forms of bovine semicarbazide-sensitive amine oxidase (EC 1.4.3.6; 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.
  01/1970: pages 105-112;