Stable multisubstrate adducts as enzyme inhibitors. Potent inhibition of ornithine decarboxylase by N-(5'-phosphopyridoxyl)-ornithine.
The synthesis of several N-(5'-phosphopyridoxyl)-amino acids is described. These compounds, analogs of the Schiff base intermediate involved in enzyme-catalyzed decarboxylation, are potent inhibitors of the cognate amino acid decarboxylases. Kinetic studies using partially purified rat liver ornithine decarboxylase, have shown that N-(5'-phosphopyridoxyl)-ornithine inhibits the enzyme in a non-competitive manner with respect to both ornithine and pyridoxal-5'-phosphate. These findings suggest that the inhibitor binds to the holoenzyme active site in place of the Schiff base intermediate.
D000818:Animals; D001665:Binding Sites; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D011485:Protein Binding; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D012545:Schiff Bases
D065108:Ornithine Decarboxylase Inhibitors; D012545:Schiff Bases; D011732:Pyridoxal Phosphate; D003907:Dexamethasone; D009952:Ornithine; D002262:Carboxy-Lyases