Characterization of xanthine oxidase inhibition by anacardic acids.
Anacardic acid, 6[8(Z), 11(Z), 14-pentadecatrienyl]salicylic acid, inhibits generation of superoxide radicals by xanthine oxidase. This inhibition does not follow a hyperbolic inhibition, depends on anacardic acid concentrations, but follows a sigmoidal inhibition. The inhibition was analyzed by using a Hill equation, and slope factor and EC(50) were 4.3+/-0.5 and 53.6+/-5.1 microM, respectively. In addition, anacardic acid inhibited uric acid formation by xanthine oxidase cooperatively. Slope factor and EC(50) were 1.7+/-0.5 and 162+/-10 microM, respectively. The results indicate that anacardic acid binds to allosteric sites near the xanthine-binding domain in xanthine oxidase. Salicylic acid moiety and alkenyl side chain in anacardic acid are associated with the cooperative inhibition and hydrophobic binding, respectively.
Masuoka
Noriyoshi
N
Department of Biochemistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikatacho, Okayama 700-8558, Japan. masuokan@md.okayama-u.ac.jp
Kubo
Isao
I
D048729:Anacardic Acids; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D007700:Kinetics; D012459:Salicylates / Q000494:pharmacology*; D014527:Uric Acid / Q000378:metabolism; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D048729:Anacardic Acids; D004791:Enzyme Inhibitors; D012459:Salicylates; D005182:Flavin-Adenine Dinucleotide; C088115:anacardic acid; D019820:Xanthine; D014527:Uric Acid; D014969:Xanthine Oxidase