Pyrraline ether crosslinks as a basis for protein crosslinking by the advanced Maillard reaction in aging and diabetes
Pyrraline ether crosslinks as a basis for protein crosslinking by the advanced Maillard reaction in aging and diabetes
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DOI：
10.1006/abbi.1996.0019
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发表时间：
1996-01-15
影响因子：
3.9
通讯作者：
Monnier, VM
中科院分区：
文献类型：
--
作者：
Nagaraj, RH;PorteroOtin, M;Monnier, VM
吡咯素（N-2-（甲酰基-5-羟甲基-吡咯-1-基）-L-正亮氨酸）是葡萄糖与蛋白质上的赖氨酸氨基反应衍生的高级美拉德反应产物，其存在于血浆和组织蛋白中已经通过免疫学和色谱方法确定，从葡萄糖和赖氨酸反应中得到的纯化的吡咯啉制剂在室温或冷藏条件下储存时变成粉红色通过高效液相色谱法分析这些产物，并将其中一种产物分离至纯度，确定该化合物的结构是由两个吡咯啉分子之间的醚键形成的二吡咯啉，这一发现使我们研究了吡咯啉与巯基和羟基氨基酸的反应性，羟基氨基酸一般不反应，除了羟基赖氨酸和羟基脯氨酸形成次要的缩合产物。虽然半胱氨酸的反应导致形成两种不同的硫醚，谷胱甘肽的反应导致形成两种主要的未鉴定的化合物，其在孵育后逐渐降解。这些数据表明，体内形成的吡咯啉可以进一步与蛋白质上的其他氨基酸反应以形成交联，这可以部分解释与衰老和糖尿病相关的蛋白质交联增加。(C)出版社：Academic Press，Inc.
Pyrraline (epsilon-2-(formyl-5-hydroxymethyl-pyrrol-1-yl)-L-norleucine) is an advanced Maillard reaction product derived from the reaction of glucose with lysine amino group on proteins, Its presence in plasma and tissue proteins has been established by immunological and chromatographic methods, The purified preparation of pyrraline obtained from the reaction of glucose with lysine when stored at room temperature or at refrigeration turned pink in color, suggesting spontaneous formation of degradation products, These products were analyzed by high-performance liquid chromatography and one of the products was isolated to purity, The structure of the compound was established to be a dipyrraline formed by an ether bond between two pyrraline molecules, This finding led us to investigate the reactivity of pyrraline with thiol and hydroxy amino acids, The hydroxy amino acids were in general nonreactive, except hydroxy lysine and hydroxy proline which formed minor condensation products. While the reaction of cysteine resulted in the formation of two distinct thioethers, the reaction of glutathione resulted in the formation of two major unidentified compounds which gradually degraded upon incubation, These data suggest that pyrraline formed in vivo can further react with other amino acids on proteins to form crosslinks, which may explain in part increased protein crosslinking associated with aging and diabetes. (C) 1996 Academic Press, Inc.