Department of Pathology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
Mol Genet Metab. 2010;100 Suppl 1:S31-6. doi: 10.1016/j.ymgme.2010.01.012. Epub 2010 Jan 29.
The paucity of hyperammonemic crises together with spasticity, only seen in human arginase I deficient patients and not in patients with other urea cycle disorders, forces a search for candidates other than ammonia to associate with the pathophysiology and symptomatology. Therefore, we determined arginine together with some catabolites of arginine in blood and cerebrospinal fluid of these patients as well as in extremely rare post-mortem brain material of two patients with argininemia. The levels of alpha-keto-delta-guanidinovaleric acid, argininic acid and alpha-N-acetylarginine correlate with the arginine levels in blood and cerebrospinal fluid of patients with imposed or spontaneous protein restriction. The levels in blood are higher than the upper limit of normal in all studied patients. In addition to the highly increased levels of these same compounds in blood of a child with argininemia, the increase of guanidinoacetic acid, 24h before death, is remarkable. However, the manifest increases of these studied catabolites of arginine are not seen in post-mortem brain material of the same pediatric patient. Otherwise a clear increase of guanidinoacetic acid in post-mortem brain material of an adult patient was shown. A similar, comparable increase of homoarginine in both studied post-mortem brain materials is observed. Therefore the study of the pathobiochemistry of arginine in argininemia must be completed in the future by the determination of the end catabolites of the nitric oxide and agmatine biosynthesis pathways in the knockouts as well as in the patients to evaluate their role, together with the here studied catabolites, as candidates for association with pathophysiology and symptomatology.
由于氨血症危象的缺乏以及痉挛，仅见于人类精氨酰酶 I 缺乏症患者，而不存在于其他尿素循环障碍患者中，这迫使我们寻找与病理生理学和症状学相关的除氨以外的候选物。因此，我们在这些患者的血液和脑脊液中以及两名精氨酸血症患者的非常罕见的死后脑组织中测定了精氨酸及其一些精氨酸的代谢产物。α-酮-δ-胍基戊酸、精氨酸和α-N-乙酰精氨酸的水平与患者强制或自发限制蛋白质时的血液和脑脊液中的精氨酸水平相关。血液中的水平高于所有研究患者的正常上限。除了在一名精氨酸血症患儿的血液中这些相同化合物的高度增加外，在死亡前 24 小时胍基乙酸的增加也很显著。然而，在相同儿科患者的死后脑组织中并未观察到这些研究的精氨酸代谢产物的明显增加。相反，在一名成年患者的死后脑组织中显示出明显的胍基乙酸增加。在两个研究的死后脑组织中都观察到同型精氨酸的明显增加。因此，在未来，必须通过测定敲除和患者中一氧化氮和胍丁胺生物合成途径的终末代谢产物来完成精氨酸血症中精氨酸的病理生物化学研究，以评估它们与这里研究的代谢产物一起作为与病理生理学和症状学相关的候选物的作用。
