Inhibition of xanthine oxidase by pterins.
The effect of a panel of pterins on xanthine oxidase was investigated by measuring formation of urate from xanthine as well as formazan production from nitroblue tetrazolium. The pterin derivatives, depending on their chemical structure, decreased urate as well as formazan generation: 200 microM neopterin and biopterin suppressed urate formation (90% from baseline) and formazan production (80% from baseline) as well. Their reduced forms, 7,8-dihydroneopterin and 5,6,7,8-tetrahydrobiopterin, showed a lesser but still strongly diminishing influence (40% from baseline). Another oxidized pterin namely leukopterin showed only a weak inhibitory effect. Xanthopterin, a known substrate of xanthine oxidase, had a strong effect on urate formation (80% inhibition), but a lesser effect on formazan production (30% reduction). When iron-(III)-EDTA complex was added to the reaction mixture all the effects were more pronounced. Superoxide dismutase, which removes superoxide anion by dismutation into oxygen, decreased formazan production in addition to pterin derivatives and had a small but enhancing effect on urate formation. Also the reductant N-acetylcysteine had an additive effect to pterins to diminish formazan production in a dose-dependent way. The results of our study suggest that depending on their chemical structure pterins reduce superoxide anion generation by xanthine oxidase.
Wede
I
I
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Altindag
Z Z
ZZ
Widner
B
B
Wachter
H
H
Fuchs
D
D
D000111:Acetylcysteine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D005562:Formazans / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010084:Oxidation-Reduction; D011622:Pterins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014527:Uric Acid / Q000378:metabolism; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D005290:Ferric Compounds; D005562:Formazans; D011622:Pterins; D013481:Superoxides; D019820:Xanthine; D014527:Uric Acid; D009580:Nitroblue Tetrazolium; D004492:Edetic Acid; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D000111:Acetylcysteine