Uric acid oxidation by peroxynitrite: multiple reactions, free radical formation, and amplification of lipid oxidation.
Level 5 - mechanism / opinion, no new human data
In vitro biochemical mechanistic experiment without living human or animal models.
PubMed 10600166 · doi:10.1006/abbi.1999.1491
What was done
The authors characterized the chemical kinetics and products of the reaction between urate and peroxynitrite using kinetic analyses, oxygen consumption measurements, spin trapping with 5,5-dimethyl-1-pyrroline N-oxide, and electrospray mass spectrometry. They also evaluated the effect of urate on peroxynitrite-mediated lipid oxidation in liposomes and low-density lipoprotein (LDL) by tracking lipid peroxides and thiobarbituric acid-reactive substances.
What was found
Urate reacted with peroxynitrite with an apparent second order rate constant of 4.8 x 10(2) M(-1) s(-1), consuming oxygen and producing allantoin, alloxan, and urate-derived radicals. Electrospray mass spectrometry identified the main radical as the aminocarbonyl radical, which amplified peroxynitrite-mediated oxidation of liposomes and LDL. The radical was not detectable during urate attack by other oxidants.
Why it matters
This study provides a specific biochemical mechanism for the prooxidant behavior of uric acid, showing how its reaction with peroxynitrite generates reactive radicals that propagate lipid peroxidation.
Limits
This is an acellular in vitro biochemical study; physiological relevance in vivo was not evaluated. The abstract reports no numerical values or effect sizes for the observed increases in lipid peroxides or thiobarbituric acid-reactive substances.
Cited by
- supports Extracellular uric acid reacts with certain radicals like peroxynitrite to remove them, but transiently generates peroxynitrite-like radicals in the process.