Inhibition of pig liver and Zea mays L. polyamine oxidase: a comparative study.
Polyamine oxidase (PAO) is involved in polyamine metabolism and production of hydrogen peroxide in animal and plants, thus representing a key system in development and programmed cell death. In the present study, the inhibitory effect of amiloride, p-aminobenzamidine, clonidine, 4',6-diamidino-2-phenyl-indole (DAPI), gabexate mesylate, guazatine, and N,N'-bis(2,3-butadienyl)-1,4-butane-diamine (MDL72527) on the catalytic activity of pig liver and Zea mays L. PAO, Lens culinaris L. and Pisum sativum L. and swine kidney copper amine oxidase, bovine trypsin, as well as neuronal constitutive nitric oxide synthase (NOS-I) was investigated. Moreover, agmatine and N(3) -prenylagmatine (G3) were observed to inhibit pig liver and Zea mays L. PAO, bovine trypsin, and NOS-I action, but were substrates for Lens culinaris L., Pisum sativum L. and swine kidney copper amine oxidase. Guazatine and G3 inhibited selectively Zea mays L. PAO with K(i) values of 7.5 x 10(-9) M and 1.5 x 10(-8) M, respectively (at pH 6.5 and 25.0 degrees C). As a whole, the data reported here represent examples of enzyme cross-inhibition, and appear to be relevant in view of the use of cationic L-arginine-and imidazole-based compounds as drugs.
Federico
R
R
Dipartimento di Biologia, Università degli Studi 'Roma Tre', Viale G. Marconi 446, I-00146 Roma, Italy.
Leone
L
L
Botta
M
M
Binda
C
C
Angelini
R
R
Venturini
G
G
Ascenzi
P
P
D000376:Agmatine / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology; D002417:Cattle; D003000:Clonidine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016670:Gabexate / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D018532:Pisum sativum / Q000201:enzymology; D013329:Structure-Activity Relationship; D013552:Swine; D014357:Trypsin / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000494:pharmacology; D003313:Zea mays / Q000201:enzymology*; D000097667:Polyamine Oxidase
D000376:Agmatine; D000584:Amiloride; D006631:Amine Oxidase (Copper-Containing); D001550:Benzamidines; D003000:Clonidine; D004791:Enzyme Inhibitors; D016670:Gabexate; D006146:Guanidines; D007211:Indoles; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D000587:Oxidoreductases Acting on CH-NH Group Donors; D014357:Trypsin; D014361:Trypsin Inhibitors; D000097667:Polyamine Oxidase; C007293:DAPI; C006500:4-aminobenzamidine; C012343:guazatine