Inhibition of glycosylation processes:: the reaction between pyridoxamine and glucose
Inhibition of glycosylation processes:: the reaction between pyridoxamine and glucose
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DOI：
10.1002/cbdv.200590074
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发表时间：
2005-01-01
影响因子：
2.9
通讯作者：
Donoso, J
中科院分区：
文献类型：
--
作者：
Adrover, M;Vilanova, B;Donoso, J
蛋白质被葡萄糖糖基化产生称为“晚期糖基化终产物”（AGEs）的有毒和免疫原性化合物，其是各种慢性疾病中病理症状的起源。在这项工作中，葡萄糖（2）和吡哆胺（1）之间的反应动力学研究-一种有效的抑制剂AGEs形成在体内和体外-进行。发现吡哆胺的NH 2基团与葡萄糖的C=O基团反应形成席夫碱9（方案2）。随后，席夫碱产生其它产物，包括化合物3、吡哆醛、吡哆醇和4-吡哆酸。化合物3抑制Amadori重排，并防止能够触发糖基化过程的其他C=O基团的形成。吡哆醛和吡哆醇也可以通过其他先前报道的机制抑制蛋白质糖基化。
Glycosylation of proteins by glucose produces toxic and immunogenic compounds called 'advanced glyclosylation end products' (AGEs), which are the origin of pathological symptoms in various chronic diseases. In this work, a kinetic study of the reaction between glucose (2) and pyridoxamine (1) - a potent inhibitor of AGEs formation both in vivo and in vitro - was conducted. The NH2 group of pyridoxamine was found to react with the C=O group of glucose to form the Schiff base 9 (Scheme 2). Subsequently, the Schiff base gives rise to other products, including compound 3, pyridoxal, pyridoxine, and 4-pyridoxic acid. Compound 3 inhibits the Amadori rearrangement, and prevents the formation of other C=O groups capable of triggering glycosylation processes. Pyridoxal and pyridoxine can also inhibit protein glycosylation via other previously reported mechanisms.