Effects of Uric Acid on Nitrosation of N-Acetylcysteine by Diethylamine NONOate and N-Acetyl-N-nitrosotryptophan

Abstract

Uric acid of human plasma concentration accelerated nitrosation of N-acetylcysteine by diethylamine NONOate at neutral pH, but diminished that of N-acetyltryptophan. Uric acid also accelerated nitrosation of N-acetylcysteine by N-acetyl-N-nitrosotryptophan, having a nitroso group on the nitrogen atom of the indole ring. N-Acetyl-S-nitrosocysteine was stable even in the presence of uric acid and N-acetyltryptophan at neutral pH, while decomposition of N-acetyl-N-nitrosotryptophan was accelerated by uric acid and N-acetylcysteine. The results indicate that uric acid receives a nitroso group from diethylamine NONOate or N-acetyl-N-nitrosotryptophan, and passes it to the thiol group of N-acetylcysteine resulting in N-acetyl-S-nitrosocysteine. This implies that uric acid may act as an effective transporter of nitric oxide to thiols resulting in accumulation of nitrosothiols in humans.