Agmatine oxidation by copper amine oxidase.
The product of agmatine oxidation catalyzed by Pisum sativum L. copper amine oxidase has been identified by means of one- and two-dimensional (1)H-NMR spectroscopy to be N-amidino-2-hydroxypyrrolidine. This compound inhibits competitively rat nitric oxide synthase type I and type II (NOS-I and NOS-II, respectively) and bovine trypsin (trypsin) activity, values of Ki being (1.1 +/- 0.1) x 10(-5) m (at pH 7.5 and 37.0 degrees C), (2.1 +/- 0.1) x 10(-5) m (at pH 7.5 and 37.0 degrees C), and (8.9 +/- 0.4) x 10(-5) m (at pH 6.8 and 21.0 degrees C), respectively. Remarkably, the affinity of N-amidino-2-hydroxypyrrolidine for NOS-I, NOS-II and trypsin is significantly higher than that observed for agmatine and clonidine binding. Furthermore, N-amidino-2-hydroxypyrrolidine and agmatine are more efficient than clonidine in displacing [(3)H]clonidine (= 1.0 x 10(-8) m) from specific binding sites in heart rat membranes, values of IC50 being (1.3 +/- 0.4) x 10(-9) m and (2.2 +/- 0.4) x 10(-8) m, respectively (at pH 7.4 and 37.0 degrees C).
Ascenzi
Paolo
P
Department of Biology, University Roma Tre, Rome, Italy. ascenzi@uniroma3.it
Fasano
Mauro
M
Marino
Maria
M
Venturini
Giorgio
G
Federico
Rodolfo
R
D000376:Agmatine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D003000:Clonidine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D054755:Imidazoline Receptors; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D010084:Oxidation-Reduction; D018532:Pisum sativum / Q000201:enzymology; D011759:Pyrrolidines / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism; D014357:Trypsin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D054755:Imidazoline Receptors; C449519:N-amidino-2-hydroxypyrrolidine; D011759:Pyrrolidines; D011955:Receptors, Drug; C410887:imidazoline I1 receptors; D000376:Agmatine; C496320:NOS1 protein, human; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D006631:Amine Oxidase (Copper-Containing); D014357:Trypsin; D003000:Clonidine