Chemical modification of proteins by methylglyoxal.
Chemical modification of proteins by methylglyoxal.
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DOI：
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发表时间：
1998-11
影响因子：
1.6
通讯作者：
T. Degenhardt;S. Thorpe;J. Baynes
中科院分区：
文献类型：
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作者：
T. Degenhardt;S. Thorpe;J. Baynes
丙酮醛是在有氧糖酵解过程中磷酸丙糖中间体自发分解而形成的。它也可以在碳水化合物（戊糖和抗坏血酸）和脂质（花生四烯酸）的氧化降解过程中形成。除了与精氨酸残基反应形成咪唑酮加合物外，甲基乙二醛还与蛋白质中的赖氨酸残基反应形成N（epsilon）-（carboxyethyl）lysine（CEL）和咪唑鎓交联，甲基乙二醛-赖氨酸二聚体（MOLD）。与乙二醛与蛋白质反应形成的糖氧化产物N（N）-（羧甲基）赖氨酸（CML）和甘氨酸-赖氨酸二聚体（GOLD）一样，CEL和MOLD随着年龄的增长而增加透镜蛋白和皮肤胶原。CML和CEL也增加了糖尿病患者的皮肤胶原蛋白，而所有四种化合物都增加了尿毒症患者的血浆蛋白。总体而言，CML、CEL、GOLD和MOLD是组织蛋白中美拉德反应的主要定量生物标志物。特别地，GOLD和MOLD以比荧光交联戊糖苷高10-50倍的浓度存在。总之，这些二羰基衍生的晚期糖基化终产物（AGEs）代表了随着年龄增长和慢性疾病（如糖尿病和动脉粥样硬化）在组织蛋白中积累的主要化学修饰。
Methylglyoxal is formed in vivo by spontaneous decomposition of triose phosphate intermediates in aerobic glycolysis. It may also be formed during oxidative degradation of both carbohydrates (pentoses and ascorbate) and lipids (arachidonate). In addition to reaction with arginine residues to form imidazolone adducts, methylglyoxal reacts with lysine residues in protein to form N(epsilon)-(carboxyethyl)lysine (CEL) and the imidazolium crosslink, methylglyoxal-lysine dimer (MOLD). Like the glycoxidation products, N(epsilon)-(carboxymethyl)lysine (CML) and glyoxal-lysine dimer (GOLD) which are formed on reaction of glyoxal with protein, CEL and MOLD increase in lens proteins and skin collagen with age. CML and CEL also increase in skin collagen in diabetes, while all four compounds increase in plasma proteins in uremia. Overall, CML, CEL, GOLD and MOLD are quantitatively the major biomarkers of the Maillard reaction in tissue proteins. GOLD and MOLD, in particular, are present at 10-50 fold higher concentrations than the fluorescent crosslink, pentosidine. Together, these dicarbonyl-derived advanced glycation endproducts (AGEs) represent the major chemical modifications that accumulate in tissue proteins with age and in chronic diseases such as diabetes and atherosclerosis.