Comparative sensitivities of purified preparations of lysyl oxidase and other amine oxidases to active site-directed enzyme inhibitors.
Recent evidence has revealed that lysyl oxidase, plasma amine oxidase and diamine oxidase each contain copper and pyrroloquinoline quinone at their active sites as cofactors essential to their catalytic functions. It thus seems likely that these enzymes will share similar mechanisms of action. Since mechanism-based inhibitors of lysyl oxidase have important chemotherapeutic potential for the control of fibrotic disease, the relative inhibitory potential of such agents toward catalytically similar amine oxidases was assessed in the present study using purified preparations of lysyl oxidase, diamine oxidase, plasma amine oxidase and the flavin-dependent mitochondrial monoamine oxidase A and B. The results indicate that there is sufficient difference between the sensitivities of lysyl oxidase and the other amine oxidases to beta-aminopropionitrile to warrant its consideration as an antifibrotic agent in vivo, while also revealing that aminoguanidine, clorgyline and deprenyl are sufficiently selective for diamine oxidase, monoamine oxidase A and monoamide oxidase B, respectively, to differentiate between lysyl oxidase and these enzymes at appropriate concentrations.
Tang
S S
SS
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
Chichester
C O
CO
Kagan
H M
HM
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000629:Aminopropionitrile / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003010:Clorgyline / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis / Q000188:drug therapy; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D008995:Monoamine Oxidase / Q000097:blood / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors*; D012642:Selegiline / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006146:Guanidines; D008996:Monoamine Oxidase Inhibitors; D000629:Aminopropionitrile; D012642:Selegiline; D000594:Amino Acid Oxidoreductases; D008249:Protein-Lysine 6-Oxidase; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D003010:Clorgyline; C004479:pimagedine