The inhibition of semicarbazide-sensitive amine oxidase by aminohexoses.
Semicarbazide-sensitive amine oxidase (EC 1.4.3.6; amine:oxygen oxidoreductase (deaminating) (copper-containing); SSAO) is a multifunctional protein. It acts under inflammatory conditions as a vascular-adhesion protein (VAP-1), mediating the adhesion of lymphocytes to vascular endothelial cells. The relationships, if any, between this adhesion function and the enzymatic functions (amine-substrate specificity and catalysis) of SSAO have not yet been defined. Since cell surface amino sugars and their derivatives are known to be involved in cell-to-cell recognition, we have investigated their possible effects on the enzyme activity of SSAO. The aminohexoses galactosamine, glucosamine and mannosamine were not oxidatively deaminated by SSAO. However, their presence during the assay of benzylamine oxidation resulted in a time-dependent inhibition. This inhibition was shown to follow saturation kinetics with respect to hexosamine concentration. Although time-dependent, the inhibition of SSAO activity was found to be reversible by dilution. In contrast, there is no such inhibition when the N-acetylamino sugar derivatives or the parent sugars (galactose, glucose and mannose) replaced the amino sugars in the reaction mixture. These results suggest that the interactions between SSAO and aminohexoses are specific and, therefore, that the cell-adhesion functions and amine-recognition functions of VAP-1/SSAO may be interlinked.
O'Sullivan
Jeffrey
J
Department of Biochemistry, Trinity College, Dublin 2, Ireland. josulli2@tcd.ie
O'Sullivan
Michael
M
Tipton
Keith F
KF
Unzeta
Mercedes
M
Del Mar Hernandez
Maria
M
Davey
Gavin P
GP
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D005688:Galactosamine / Q000494:pharmacology*; D005944:Glucosamine / Q000494:pharmacology*; D006595:Hexosamines / Q000494:pharmacology*; D007700:Kinetics; D012663:Semicarbazides / Q000494:pharmacology*
D006595:Hexosamines; D012663:Semicarbazides; C008322:mannosamine; D005688:Galactosamine; D006631:Amine Oxidase (Copper-Containing); D005944:Glucosamine