20 research outputs found
Reaction of uric acid with peroxynitrite and implications for the mechanism of neuroprotection by uric acid
Peroxynitrite, a biological oxidant formed from the reaction of nitric
oxide with the superoxide radical, is associated with many pathologies,
including neurodegenerative diseases, such as multiple sclerosis (MS),
Gout (hyperuricemic) and MS are almost mutually exclusive, and uric acid
has therapeutic effects in mice with experimental allergic
encephalomyelitis, an animal disease that models MS, This evidence
suggests that uric acid may scavenge peroxynitrite and/or
peroxynitrite-derived reactive species. Therefore, we studied the
kinetics of the reactions of peroxynitrite with uric acid from pH 6.9 to
8.0, The data indicate that peroxynitrous acid (HOONO) reacts with the
uric acid monoanion with k = 155 M-1 s(-1) (T = 37 degrees C, pH 7.4)
giving a pseudo-first-order rate constant in blood plasma
k(Uratc/plasma) = 0.05 s(-1) (T = 37 degrees C, pH 7.4; assuming [uric
acid](plasma) = 0.3 mM). Among the biological molecules in human plasma
whose rates of reaction with peroxynitrite have been reported, CO, is
one of the fastest with a pseudo-first-order rate constant k(co2/plasma)
= 46 s(-1) (T = 37 degrees C, pH 7.4; assuming [CO2](plasma) = 1 mM).
Thus peroxynitrite reacts with CO2 in human blood plasma nearly 920
times faster than with uric acid. Therefore, uric acid does not directly
scavenge peroxynitrite because uric acid can not compete for
peroxynitrite with CO,. The therapeutic effects of uric acid may be
related to the scavenging of the radicals CO3.- and NO; that are formed
from the reaction of peroxynitrite with CO,. We suggest that trapping
secondary radicals that result from the fast reaction of peroxynitrite
with CO, may represent a new and viable approach for ameliorating the
adverse effects associated with peroxynitrite in many diseases. (C) 2000
Academic Press