Protein modification by methylglyoxal: Chemical nature and synthetic mechanism of a major fluorescent adduct
Protein modification by methylglyoxal: Chemical nature and synthetic mechanism of a major fluorescent adduct
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DOI：
10.1006/abbi.1997.0195
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发表时间：
1997-08-01
影响因子：
3.9
通讯作者：
Nagaraj, RH
中科院分区：
文献类型：
--
作者：
Shipanova, IN;Glomb, MA;Nagaraj, RH
蛋白质的非酶美拉德反应，由糖和其他醛酮的加成引发，被认为是衰老和糖尿病并发症发病机制的重要机制。α-二羰基化合物被认为是该反应中的关键中间体。甲基乙二醛（MG）（乙醛），一种生理上的α-二羰基化合物，已被证明可以在体外和体内修饰蛋白质。在这里，我们描述了一种新的荧光嘧啶，N-δ-（5-羟基-4，6-二甲基嘧啶-2-基）-L-鸟氨酸（arg嘧啶），由MG与N-α-t-BOC-精氨酸的美拉德反应形成。我们发现，精氨酸嘧啶的荧光光谱是类似的甲基甘氨酸修饰的蛋白质，这表明它是一个主要的产品，在这样的修饰蛋白质。与甲基乙二醛孵育的蛋白质中的精氨酸嘧啶的HPLC定量揭示了时间依赖性的形成。我们在N-α-t-BOC-精氨酸与微摩尔浓度的MG的孵育中检测到显著量的精氨酸嘧啶，并且我们发现各种糖和抗坏血酸充当前体。我们的研究表明精氨酸嘧啶通过中间体3-羟基戊烷-2，4-二酮合成，并为甲基乙二醛修饰的蛋白质中的荧光提供化学基础，我们认为，糖尿病蛋白质中增强的内源性荧光可能部分是由于甲基甘氨酸介导的美拉德反应。(C)北京：科学出版社.
The nonenzymatic Maillard reaction of proteins, initiated by the addition of sugars and other aldehydes and ketones, is thought to be an important mechanism in aging and the pathogenesis of diabetic complications. The alpha-dicarbonyl compounds are considered to be key intermediates in this reaction. Methylglyoxal (MG) (pyruvaldehyde), a physiological alpha-dicarbonyl compound, has been shown to modify proteins both in vitro and in vivo. Here we describe a novel fluorescent pyrimidine, N-delta-(5-hydroxy-4,6-dimethylpyrimidine-2-yl)-L-ornithine (argpyrimidine), formed from the Maillard reaction of MG with N-alpha-t-BOC-arginine. We find that the fluorescence spectrum of argpyrimidine is similar to that of methylglyoxal-modified proteins, suggesting that it is a major product in such modified proteins. HPLC-quantification of argpyrimidine in proteins incubated with methylglyoxal revealed a time-dependent formation. We detected significant amounts of argpyrimidine in incubations of N-alpha-t-BOC-arginine with micromolar concentrations of MG, and we find that various sugars and ascorbic acid serve as precursors, Our studies indicate that argpyrimidine is synthesized through an intermediate 3-hydroxypentane-2,4-dione and provide a chemical basis for fluorescence in proteins modified by methylglyoxal, We suggest that enhanced intrinsic fluorescence in diabetic proteins may be due, in part, to methylglyoxal-mediated Maillard reactions. (C) 1997 Academic Press.