Mechanisms for the formation of protein-bound homocysteine in human plasma.
Mechanisms for the formation of protein-bound homocysteine in human plasma.
复制标题
DOI：
10.1006/bbrc.2000.3723
复制
发表时间：
2000-11
影响因子：
3.1
通讯作者：
T. Togawa;S. Sengupta;H. Chen;K. Robinson;I. Nonevski;A. Majors;D. Jacobsen
中科院分区：
文献类型：
--
作者：
T. Togawa;S. Sengupta;H. Chen;K. Robinson;I. Nonevski;A. Majors;D. Jacobsen
高同型半胱氨酸血症是心血管疾病的独立危险因素。循环中超过70%的同型半胱氨酸是蛋白结合的。建立了人血浆同型半胱氨酸的体外模型，用于研究蛋白结合同型半胱氨酸的形成机制，并建立血浆同型半胱氨酸的平衡结合能力。血浆中加入同型半胱氨酸引起半胱氨酸的初始快速置换，随后蛋白结合同型半胱氨酸增加。这种快速反应之后是一个较慢的氧依赖性反应，形成额外的蛋白质结合的同型半胱氨酸。为了测定血浆蛋白对高半胱氨酸的平衡结合能力，在有氧条件下用0.5-10 mM dl-高半胱氨酸在37 ℃处理血浆4小时。在这些条件下，男性（n = 10）和女性（n = 10）供体的平衡结合容量分别为4.88 +/- 0.51和4.74 +/- 0.68微摩尔/克蛋白质。蛋白结合同型半胱氨酸形成的机制涉及硫醇-二硫键交换和硫醇氧化反应。我们的结论是，血浆蛋白具有高的能力，在体外结合同型半胱氨酸。
Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Greater than 70% of homocysteine in circulation is protein-bound. An in vitro model system using human plasma has been developed to study mechanisms of protein-bound homocysteine formation and establish the equilibrium binding capacities of plasma for homocysteine. Addition of homocysteine to plasma caused an initial rapid displacement of cysteine and a subsequent increase in protein-bound homocysteine. This rapid reaction was followed by a slower oxygen-dependent reaction forming additional protein-bound homocysteine. To determine the equilibrium binding capacity of plasma proteins for homocysteine, plasma was treated with 0.5-10 mM dl-homocysteine for 4 h at 37 degrees C under aerobic conditions. Under these conditions the equilibrium binding capacity was 4.88 +/- 0.51 and 4.74 +/- 0.68 micromol/g protein for male (n = 10) and female (n = 10) donors, respectively. The mechanism of protein-bound homocysteine formation involves both thiol-disulfide exchange and thiol oxidation reactions. We conclude that plasma proteins have a high capacity for binding homocysteine in vitro.