Oxidative stress in urea cycle disorders: Findings from clinical and basic research

Inborn errors of metabolism (IEM) comprise a group of over 600 disorders, each with a specific metabolic impairment due to a genetic defect. Urea cycle disorders (UCD) are IEM that affect the nitrogen disposal system, leading to hyperammonemia and the accumulation of other toxic metabolites in tissues of affected patients. UCD arise from mutations in the genes coding any of the enzymes participating in the urea cycle, either directly or as regulators of this pathway, causing severe respiratory alkalosis. Considering that the exact mechanisms underlying the damage found in UCD, the purpose of this minireview is to obtain data and search for links between UCD and oxidative stress, a phenomenon common to several IEM. In vitro studies and animal models of UCD suggest that, not only the accumulation of ammonia, but also of the other metabolites involved in each UCD may impair redox status. Nitric oxide metabolism also seems to play an interesting role in the maintenance of redox balance in these conditions. Clinical research provides little information on the subject, but, studies appear to support the role of oxidative stress in pathologic mechanisms of UCD.