Disturbance of Nitrogen Metabolism in sparse-fur mice.

本文研究了稀毛雀的氮代谢。或鸟氨酸转氨甲酰酶（OTC）缺陷小鼠。Spf小鼠的肝脏和肠道中存在动力学异常的OTC，这将导致高氨血症和精氨酸缺乏。后者是正确的;他们在年轻和老年时血清和大脑中的瓜氨酸和精氨酸浓度都很低。而spf小鼠的血清氨浓度在成年期并没有升高。只有在断奶期间的两到三个星期，他们表现出血清氨水平升高。考虑到这些结果，我们比较了spf小鼠在高氨血症阶段（30 - 45日龄）和适应阶段（50日龄后）的氮代谢。在高氨血症阶段，脑内氨浓度升高，其水平与脑内谷氨酰胺浓度相关。后者与苯丙氨酸、酪氨酸和色氨酸的浓度相关。在此阶段，5-羟色胺的代谢受到刺激，根据5-羟色胺与5-羟吲哚乙酸的较高比率判断。这可能会导致高氨血症的一些神经症状。在这两个阶段，大脑中的瓜氨酸和精氨酸水平都非常低。为了检测spf小鼠对氨的解毒能力，进行了肝脏灌流实验。Spf小鼠表现出较低的由铵盐生成尿素的活性，尤其是在不添加鸟氨酸的情况下。这可能表明OTC在SPF小鼠中的异常动力学性质。两个阶段的尿乳清酸浓度都很高，再次证明是OTC缺乏的良好标志物。

In the present study, nitrogen metabolism of sparse-fur (spf). or ornithine transcarbamylase (OTC)-deficient mice was investigated. Spf mice have kinetically abnormal OTC in the liver and intestine,which would cause hyperammonemia and arginine deficiency. The latter was true; they showed low citrulline and arginine concentrations in the serum and in the brain always at the young and old ages. Serum ammonia concentration of spf mice, however, was not elevated at the adult ages. Only during the weaning period for two to three weeks, they showed elevated serum ammonia levels. Considering these results, we compared nitrogen metabolism of spf mice between hyperammonemic stage (30 to 45 days old) and adapted stage (after 50 days old). At hyperammonemic stage, ammonia concentration was elevated in the brain and the level was correlated with the concentrations of glutamine in the brain. And the latter level was corelated with the concentrations of phenylalanine, tyrosine and tryptophan. At this stage,metabolism of 5-hydroxytryptamine was stimulated, as judged from the higher ratio of 5-hydroxytryptamine to 5-hyroxyindole acetic acid. This may cause some neurological symptoms of hyperammonemia. At both stages, levels of citrulline and arginine in the brain were very low. In order to test the ability of ammonia detoxication in the spf mice, liver perfusion experiments were performed. Spf mice showed the lower activity of urea formation from ammonium salt especially under no addition of ornithine. which may be indicative of abnormal kinetic properties of OTC in spf mice. Urinary orotic acid concentration was very high at both stages and is again shown to be a good marker for OTC deficiency.