Nitrosation of N-methyl derivatives of uric acid and their transnitrosation ability to N-acetylcysteine.
When 1,3-dimethyluric acid was treated with a nitric oxide donor, diethylamine NONOate, in an aerobic neutral solution and the reaction was analyzed by HPLC, 1,3-dimethyluric acid was consumed to yield a nitrosated derivative, which decomposed with a half-life of 17.9 min at pH 7.4 and 37 degrees C. When 1,3,7-trimethyluric acid was treated with diethylamine NONOate, no consumption of 1,3,7-trimethyluric acid was observed. However, in the reaction of N-acetylcysteine with diethylamine NONOate, the yield of N-acetyl-S-nitrosocysteine increased by the addition of 1,3,7-trimethyluric acid as well as 1,3-dimethyluric acid. For 1,3,7,9-tetramethyluric acid, no consumption in the reaction with diethylamine NONOate and no effect on the S-nitrosation were observed. These results suggest that 1,3-dimethyluric and 1,3,7-trimethyluric acids are both nitrosated by diethylamine NONOate on the nitrogen atom of their oxoimidazole ring, although the half-life of the nitrosated 1,3,7-trimethyluric acid is too short to detect by HPLC. Consequently, these two acids can act as vehicles of nitric oxide.
Suzuki
Toshinori
T
School of Pharmacy, Shujitsu University, Okayama 703-8516, Japan. tsuzuki@shujitsu.ac.jp
Yamamoto
Hiroshi
H
Pfleiderer
Wolfgang
W
D000111:Acetylcysteine / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry*; D015538:Nitrosation; D014527:Uric Acid / Q000031:analogs & derivatives* / Q000737:chemistry
D014527:Uric Acid; D009569:Nitric Oxide; C039222:1,3,7-trimethyluric acid; C031274:1,3-dimethyluric acid; D000111:Acetylcysteine