L-lysine as a recognition molecule for the VAP-1 function of SSAO.
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 H(2)O(2) 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 H(2)O(2) formed during benzylamine oxidation. The possible implications of this in terms of the therapeutic uses of lysine are discussed.
Olivieri
A
A
School of Biochemistry and Immunology, Trinity College, Dublin, Ireland. oliviera@tcd.ie
Tipton
K
K
O'Sullivan
J
J
D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001596:Benzylamines / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000201:enzymology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D008239:Lysine / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D011485:Protein Binding / Q000502:physiology; D013997:Time Factors
D001596:Benzylamines; D015815:Cell Adhesion Molecules; D006861:Hydrogen Peroxide; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); D008239:Lysine