Teerlink Tom
Metabolic Laboratory, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
Clin Chem Lab Med. 2005;43(10):1130-8. doi: 10.1515/CCLM.2005.197.
Asymmetric dimethylarginine (ADMA) is a potent inhibitor of nitric oxide synthase and is regarded as a novel risk factor for cardiovascular disease. The metabolic pathways of ADMA and homocysteine are strongly intertwined. First, during synthesis of ADMA, two equivalents of homocysteine are formed. Second, homocysteine has been shown to inhibit the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase. Finally, homocysteine, either directly or by increasing oxidative stress, may promote release of free ADMA by accelerating protein degradation. Currently used techniques for the quantification of ADMA in plasma are mostly based on liquid chromatography with fluorimetric or mass spectrometric detection. Plasma ADMA has a very narrow concentration distribution, with an inter-individual coefficient of variation of approximately 12%, and even slightly elevated ADMA concentrations are associated with increased cardiovascular disease risk. Therefore, to generate useful results in clinical research, high precision of the assay used for the quantification of ADMA assay is a matter of prime importance. Assays with a high coefficient of variation may lead to low statistical power in clinical trials and to a severe underestimation of the strength of associations in epidemiological studies.
不对称二甲基精氨酸（ADMA）是一氧化氮合酶的强效抑制剂，被视为心血管疾病的一种新的危险因素。ADMA和同型半胱氨酸的代谢途径紧密相连。首先，在ADMA合成过程中，会生成两分子同型半胱氨酸。其次，已证明同型半胱氨酸可抑制降解ADMA的二甲基精氨酸二甲胺水解酶。最后，同型半胱氨酸可直接或通过增加氧化应激，加速蛋白质降解来促进游离ADMA的释放。目前用于定量血浆中ADMA的技术大多基于液相色谱与荧光或质谱检测。血浆ADMA的浓度分布非常狭窄，个体间变异系数约为12%，即使ADMA浓度略有升高也与心血管疾病风险增加相关。因此，为在临床研究中得出有用结果，用于定量ADMA分析的检测方法具有高精度至关重要。变异系数高的检测方法可能导致临床试验中的统计效能低下，并严重低估流行病学研究中关联的强度。
