Wanby P, Brattström L, Brudin L, Hultberg B, Teerlink T
Department of Medicine, County Hospital, Kalmar, Sweden.
Scand J Clin Lab Invest. 2003;63(5):347-53. doi: 10.1080/00365510310002040.
Elevation of homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) in plasma are believed to be involved in the pathogenesis of cardiovascular disease (CVD). In humans, oral methionine loading results in acute elevation of plasma Hcy. This is associated with impaired NO-dependent vasodilatation, a mechanism that may explain the relationship between elevated Hcy and risk of CVD. ADMA, an endogenous competitive inhibitor of NO-synthase, may be elevated in plasma of patients with CVD. It was proposed that ADMA is synthesized in a methionine-dependent reaction which also forms Hcy. In this study plasma total homocysteine (tHcy) and ADMA concentrations were measured before and after oral methionine loading of human subjects.
Plasma tHcy and ADMA levels were measured in 12 healthy males (age 32-58 years) before and after oral loading with L-methionine (100 mg/kg body weight in orange juice).
At noon, 4 h after methionine loading, tHcy and ADMA levels (35.4 +/- 10.9 and 0.80 +/- 0.13 micromol/L, mean +/- SD) were significantly higher than the corresponding values obtained at noon the day before (15.6 +/- 7.4 and 0.63 +/- 0.10 micromol/L, both p<0.001). Noon values 4 h after methionine loading were also significantly higher than values obtained immediately before the methionine load (13.7 +/- 5.9 and 0.66 +/- 0.10 micromol/L, both p<0.001). Reinvestigation of 8 of 12 subjects showed that at 4 and 8 h after compared with levels immediately before methionine loading there was a significant increase in tHcy (28.4 +/- 10.2 and 33.45 +/- 11.1 vs. 10.8 +/- 3.3 micromol/L, both p<0.001). However, the corresponding ADMA levels did not increase (0.73 +/- 0.17 and 0.76 +/- 0.22 vs. 0.70 +/- 0.10 micromol/L, both not significant).
No clear evidence was found to support the supposition that methionine-induced hyperhomocysteinaemia may be accompanied by elevated levels of ADMA, an endogenous competitive NO-synthase inhibitor that may represent an alternative pathogenic mechanism for homocysteine-associated impairment of endothelial NO-dependent functions.
血浆中同型半胱氨酸（Hcy）和不对称二甲基精氨酸（ADMA）水平升高被认为与心血管疾病（CVD）的发病机制有关。在人类中，口服蛋氨酸负荷会导致血浆Hcy急性升高。这与一氧化氮（NO）依赖性血管舒张功能受损有关，这一机制可能解释了Hcy升高与CVD风险之间的关系。ADMA是一种内源性NO合酶竞争性抑制剂，在CVD患者的血浆中可能升高。有人提出，ADMA是在一个依赖蛋氨酸的反应中合成的，该反应也会生成Hcy。在本研究中，对人类受试者口服蛋氨酸负荷前后的血浆总同型半胱氨酸（tHcy）和ADMA浓度进行了测量。
在12名健康男性（年龄32 - 58岁）口服L - 蛋氨酸（100 mg/kg体重，溶于橙汁中）前后，测量其血浆tHcy和ADMA水平。
在中午，即蛋氨酸负荷后4小时，tHcy和ADMA水平（35.4±10.9和0.80±0.13 μmol/L，均值±标准差）显著高于前一天中午测得的相应值（15.6±7.4和0.63±0.10 μmol/L，p均<0.001）。蛋氨酸负荷后4小时的中午值也显著高于蛋氨酸负荷前即刻测得的值（13.7±5.9和0.66±0.10 μmol/L，p均<0.001）。对12名受试者中的8名进行再次检测发现，与蛋氨酸负荷前即刻相比，在负荷后4小时和8小时tHcy显著升高（28.4±10.2和33.45±11.1 vs. 10.8±3.3 μmol/L，p均<0.001）。然而，相应的ADMA水平并未升高（0.73±0.17和0.76±0.22 vs. 0.70±0.10 μmol/L，均无统计学意义）。
未发现明确证据支持蛋氨酸诱导的高同型半胱氨酸血症可能伴有ADMA水平升高这一假设，ADMA是一种内源性竞争性NO合酶抑制剂，可能代表同型半胱氨酸相关的内皮NO依赖性功能损害的另一种致病机制。
