Identifying a role for the interaction of homocysteine and copper in promoting cardiovascular-related damage
Identifying a role for the interaction of homocysteine and copper in promoting cardiovascular-related damage
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DOI：
10.1007/s00726-021-02979-9
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发表时间：
2021-04-22
期刊：
影响因子：
3.5
通讯作者：
Strongin, Robert M.
中科院分区：
文献类型：
--
作者：
Gupta, Megha;Meehan-Atrash, Jiries;Strongin, Robert M.
心血管疾病患者中铜和同型半胱氨酸水平同时升高的观察结果引起了人们对研究铜和同型半胱氨酸之间相互作用的兴趣。先前的几项研究表明，铜和同型半胱氨酸的复合物具有毒性，会导致体外心血管损伤。然而，尚不清楚为什么其他结构相似、含量更丰富的细胞硫醇（例如谷胱甘肽和半胱氨酸）不会出现相关效应。在此，证明了铜和同型半胱氨酸之间选择性氧化还原相互作用的机制。它涉及动力学上有利的分子内氢原子转移，从而产生以α-氨基碳为中心的自由基，已知该自由基会促进生物分子损伤。
Observations that copper and homocysteine levels are simultaneously elevated in patients with cardiovascular disease has generated interest in investigating the interactions between copper and homocysteine. Several prior studies have shown that complexes of copper and homocysteine are toxic, leading to cardiovascular damage in vitro. It is not clear, however, why related effects do not occur with other structurally similar, more abundant cellular thiols such as glutathione and cysteine. Herein, a mechanism for a selective redox interaction between copper and homocysteine is demonstrated. It involves a kinetically favored intramolecular hydrogen atom transfer that results in an alpha-amino carbon-centered radical known to promote biomolecular damage.