Disturbance of Nitrogen Metabolism in sparse-fur mice.

在本研究中，研究了稀毛(SPF)的氮代谢。或鸟氨酸转氨甲基酶(OTC)缺陷小鼠。SPF小鼠存在肝脏和肠道OTC动力学异常，可引起高氨血症和精氨酸缺乏。后者是正确的；他们在血清和大脑中的瓜氨酸和精氨酸浓度总是很低，无论是在年轻人还是老年人。然而，SPF小鼠的血氨浓度在成年时并没有升高。只有在断奶两到三周期间，它们的血氨水平才会升高。考虑到这些结果，我们比较了SPF小鼠在高氨期(30~45日龄)和适应期(50日龄后)的氮代谢。在高氨期，脑内氨浓度升高，并与脑内谷氨酰胺浓度呈正相关。而后者与苯丙氨酸、酪氨酸、色氨酸浓度呈正相关。在这个阶段，从5-羟色胺与5-羟基吲哚乙酸的比例较高来判断，5-羟色胺的代谢被刺激。这可能会导致一些神经症状的高氨血症。在这两个阶段，大脑中的瓜氨酸和精氨酸水平都很低。为了检测SPF小鼠的氨解毒能力，进行了肝脏灌流实验。SPF小鼠表现出从铵盐生成尿素的活性较低，特别是在不添加鸟氨酸的情况下。这可能表明SPF小鼠OTC的动力学特性异常。在这两个阶段，尿花黄酸浓度都非常高，再次被证明是OTC缺乏的一个很好的标志。

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.