NUCLEOTIDE POOL IMBALANCES IN THE LIVERS OF PATIENTS WITH UREA CYCLE DISORDERS ASSOCIATED WITH INCREASED LEVELS OF OROTIC ACIDURIA

Liver samples obtained at autopsy from patients with ornithine transca rbamylase (OTC) deficiency, a urea cycle disorder that is associated w ith high levels of erotic acid biosynthesis and excretion were analyse d for nucleotide pools. As a control, liver samples from patients with a deficiency of mitochondrial carbamyl phosphate synthetase (CPS-I) w hich is not associated with increased levels of erotic acidurias were also analysed. The results show that liver tissue from OTC deficiency patients exhibited an increased ratio of uridine nucleotides to adenos ine nucleotides, while in CPS-I deficiency patients, no such increase was noted. This study indicates that genetic disorders that are associ ated with increased loads of erotic acid exhibit abnormally high ratio s of uridine to adenosine nucleotides in the liver. This type of imbal ance is analogous to that seen in the liver of rats and mice exposed t o an erotic acid supplemented or an arginine-deficient diet under live r tumor promoting conditions. It is likely that an imbalance in nucleo tide pools may have a significant role in the pathophysiology associat ed with these disorders.