NG, NG-dimethylarginine and NG, N′G-dimethylarginine in renal insufficiency

NG, NG-dimethylarginine and NG, N′G-dimethylarginine in renal insufficiency
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DOI:
10.1007/s004240050973
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发表时间:
2000-03-01
影响因子:
4.5
通讯作者:
De Deyn, PP
De Deyn, PP
中科院分区:
医学3区
文献类型:
--
作者:
Al Banchaabouchi, M;Marescau, B;De Deyn, PP

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不对称N-G,N-G-二甲基精氨酸(ADMA)和对称N-G,N'(G)-二甲基精氨酸(SDMA)是具有胍基的碱性内源氨基酸。我们对二甲基精氨酸的肾脏分布研究清楚地表明,在小鼠和大鼠中,ADMA和SDMA水平以蛋白质结合化合物的形式最为丰富(95%)。ADMA几乎占蛋白质结合二甲基精氨酸量的90%。研究的四个区域(皮层、外髓质内外条纹、内髓质)含有或多或少相同数量的蛋白结合二甲基精氨酸;两种游离二甲基精氨酸的浓度在不同区域变化较大。测定了人、大鼠和小鼠的血浆和尿排泄水平,并比较了它们在肾功能不全时的变化。在人和大鼠中,血浆二甲基精氨酸水平和肌酐清除率之间存在高度显著的负相关。尿ADMA排泄水平与肌酐清除率之间的相关性在人和小鼠中都非常显著且呈正相关,而在大鼠中则呈负相关。在严重肾功能不全患者中,ADMA清除率仅为对照组的9.5%,SDMA清除率仅为7.8%。肾切除小鼠对ADMA和SDMA的清除率分别为对照组的60.5%和53.8%,而肾切除大鼠对ADMA和SDMA的清除率为对照组的53.8%。ADMA清除率实际上增加了5.4倍,SDMA清除率没有明显变化。人、大鼠和小鼠在新陈代谢方面既有相似之处,也有不同之处。
Asymmetric N-G,N-G-dimethylarginine (ADMA) and symmetric N-G,N'(G)-dimethylarginine (SDMA) are basic endogenous amino acids with a guanidino group. Our renal distribution study of dimethylarginines clearly indicates that, in mouse and rat, ADMA and SDMA levels are most abundant as protein-incorporated compounds (95%). ADMA represents almost 90% of this protein-incorporated dimethylarginine amount. The four zones studied (cortex, outer and inner stripe of outer medulla, inner medulla) contain more or less the same amount of protein-incorporated dimethylarginine; the concentrations of both free dimethylarginines vary more in the different zones. Plasma and urinary excretion levels in Man, rat and mouse were determined, their chang rs in renal insufficiency were examined and compared between species. Highly significant negative correlations between both plasma dimethylarginine levels and creatinine clearances were found in Man and rat. The correlation between urinary ADMA excretion levels and creatinine clearances was highly significant and positive in Man and mouse: however, in rat the correlation was negative. In patients with severe renal insufficiency, ADMA clearance was only 9.5% of controls, and that of SDMA only 7.8%. Clearance of ADMA and SDMA in nephrectomized mice was 60.5% and 53.8% of controls, respectively, whereas in nephrectomized rat. ADMA clearance actually increased 5.4 times and that of SDMA did nor change significantly. Man, rat and mouse show similarities as well as differences in metabolism.