Garibotto Giacomo, Sofia Antonella, Saffioti Stefano, Russo Rodolfo, Deferrari Giacomo, Rossi Daniela, Verzola Daniela, Gandolfo Maria Teresa, Sala Maria Rita
Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E757-63. doi: 10.1152/ajpendo.00403.2002. Epub 2002 Dec 10.
In the present study, we used organ balance across the kidney, splanchnic organs, and lower limb in subjects undergoing diagnostic central venous catheterizations to gain insight into the renal and extrarenal exchange of aminothiols in humans. Although Hcy was released only in low amounts from leg tissues, Cys-Gly (a peptide derived from GSH hydrolysis) was released by both the leg and splanchnic organs, whereas Cys was released by the kidney and taken up by splanchnic organs. The kidney removed approximately 90% of the Cys-Gly released into the circulation. Removal of Cys-Gly by the kidney depended on Cys-Gly arterial levels and showed a high fractional extraction ( approximately 26%), with clearance rates slightly higher than the glomerular filtration rate (GFR). Although the average kidney removal of Hcy was not statistically significant, the fractional extraction of Hcy across the kidney varied directly with renal plasma flow. Our data show that thiol metabolism in humans is a compartmentalized interorgan process involving fluxes of individual aminothiols that are parallel and of opposite sign among peripheral tissues, splanchnic organs, and kidney. Cys-Gly is released by peripheral tissue and splanchnic organs from GSH hydrolysis and is taken up by the kidney by GFR; the kidney returns Cys to the circulation to preserve substrate availability for GSH synthesis. On the other hand, Hcy is released by peripheral tissues in low amounts, and its removal by the kidney seems to depend on blood supply. These findings may help explain several alterations in aminothiol metabolism observed in patients with chronic diseases.
在本研究中，我们对接受诊断性中心静脉置管的受试者的肾脏、内脏器官和下肢进行了器官平衡分析，以深入了解人体中氨基硫醇的肾内和肾外交换情况。尽管同型半胱氨酸（Hcy）仅从腿部组织中少量释放，但胱氨酸 - 甘氨酸（一种由谷胱甘肽水解产生的肽）由腿部和内脏器官释放，而胱氨酸（Cys）由肾脏释放并被内脏器官摄取。肾脏清除了循环中约90%的胱氨酸 - 甘氨酸。肾脏对胱氨酸 - 甘氨酸的清除取决于其动脉水平，并显示出较高的分数提取率（约26%），清除率略高于肾小球滤过率（GFR）。尽管肾脏对Hcy的平均清除在统计学上不显著，但Hcy在肾脏中的分数提取与肾血浆流量直接相关。我们的数据表明，人体中的硫醇代谢是一个器官间的分区过程，涉及外周组织、内脏器官和肾脏中单个氨基硫醇的平行且方向相反的通量。胱氨酸 - 甘氨酸由外周组织和内脏器官通过谷胱甘肽水解释放，并通过肾小球滤过率被肾脏摄取；肾脏将胱氨酸返回循环以维持谷胱甘肽合成的底物可用性。另一方面，Hcy由外周组织少量释放，其被肾脏清除似乎取决于血液供应。这些发现可能有助于解释在慢性病患者中观察到的氨基硫醇代谢的几种改变。
