Vasudevan S, Qureshi I A, Lambert M, Rao P M, Rajalakshmi S, Sarma D S
Department of Pathology, University of Toronto, Ontario, Canada.
Biochem Mol Biol Int. 1995 Mar;35(3):685-90.
Liver samples obtained at autopsy from patients with ornithine transcarbamylase (OTC) deficiency, a urea cycle disorder that is associated with high levels of orotic acid biosynthesis and excretion were analysed for nucleotide pools. As a control, liver samples from patients with a deficiency of mitochondrial carbamyl phosphate synthetase (CPS-I) which is not associated with increased levels of orotic acidurias were also analysed. The results show that liver tissue from OTC deficiency patients exhibited an increased ratio of uridine nucleotides to adenosine nucleotides, while in CPS-I deficiency patients, no such increase was noted. This study indicates that genetic disorders that are associated with increased loads of orotic acid exhibit abnormally high ratios of uridine to adenosine nucleotides in the liver. This type of imbalance is analogous to that seen in the liver of rats and mice exposed to an orotic acid supplemented or an arginine-deficient diet under liver tumor promoting conditions. It is likely that an imbalance in nucleotide pools may have a significant role in the pathophysiology associated with these disorders.
对尸检时从鸟氨酸转氨甲酰酶（OTC）缺乏症患者获取的肝脏样本进行了核苷酸池分析，OTC缺乏症是一种尿素循环障碍，与乳清酸生物合成和排泄水平升高有关。作为对照，还分析了线粒体氨甲酰磷酸合成酶（CPS-I）缺乏症患者的肝脏样本，该缺乏症与乳清酸尿水平升高无关。结果显示，OTC缺乏症患者的肝脏组织中尿苷核苷酸与腺苷核苷酸的比例增加，而在CPS-I缺乏症患者中未观察到这种增加。这项研究表明，与乳清酸负荷增加相关的遗传疾病在肝脏中表现出尿苷与腺苷核苷酸的异常高比例。这种失衡类似于在肝脏肿瘤促进条件下，喂食补充乳清酸或缺乏精氨酸饮食的大鼠和小鼠肝脏中所见的失衡。核苷酸池的失衡可能在与这些疾病相关的病理生理学中起重要作用。
