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

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 H(2)O(2) was, however, found to result in time-dependent inhibition. This is not a result of the non-enzymic reaction between H(2)O(2) and the amino sugar, since preincubation of galactosamine with H(2)O(2) alone, for extended periods, did not give rise to an inhibitory species. The amount of exogenously added H(2)O(2) necessary for inhibition was very much greater than that formed during substrate oxidation. These results suggest that the H(2)O(2) formed as a product of the SSAO-catalysed oxidation reaction is more efective in promoting the binding of amino sugars.