Koenig R J, Blobstein S H, Cerami A
J Biol Chem. 1977 May 10;252(9):2992-7.
Hemoglobin AIc is a minor component of normal adult erythrocytes whose concentration is elevated approximately 2-fold in patients with diabetes mellitus. Previous work suggested that the unique structural feature of hemoglobin AIc is the presence of a low molecular weight sugar moiety at the NH2-terminal valine of the beta chain. In this study the structure of the carbohydrate moiety and the nature of its linkage of the beta chain were investigated. Enzymatic digestion of borohydride-reduced betaAIc chains followed by ion exchange chromatography led to the isolation of two distinct NH2-terminal glycovalylhistidines. Comparison of these glycodipeptides with synthetic glycovalylhistidines by thin layer chromatography, gas-liquid chromatography, and proton magnetic resonance spectroscopy gave direct evidence that the naturally derived materials correspond to glucitol and mannitol valylhistidines. Model reactions showed that glucose and mannose react with valine under mild conditions to form an adduct which upon sodium borohydride reduction yields in both cases glucitol and mannitol valines. This suggests a common intermediate, 1-deoxy-1-(N-valyl)fructose, for both reactions. From these studies we conclude that hemoglobin AIc has, as the NH2 terminus of the beta chain, 1-deoxy-1-(N-valyl)fructose. The possible biosynthetic pathways of hemoglobin AIc are discussed.
糖化血红蛋白A1c是正常成人红细胞的一种次要成分，在糖尿病患者中其浓度会升高约2倍。先前的研究表明，糖化血红蛋白A1c的独特结构特征是在β链的NH2末端缬氨酸处存在一个低分子量糖部分。在本研究中，对碳水化合物部分的结构及其与β链的连接性质进行了研究。用离子交换色谱法对硼氢化钠还原的βA1c链进行酶促消化，从而分离出两种不同的NH2末端糖基化缬氨酰组氨酸。通过薄层色谱、气液色谱和质子磁共振光谱法将这些糖肽与合成糖基化缬氨酰组氨酸进行比较，直接证明天然来源的物质对应于葡糖醇和甘露糖醇缬氨酰组氨酸。模型反应表明，葡萄糖和甘露糖在温和条件下与缬氨酸反应形成加合物，在两种情况下，经硼氢化钠还原后均生成葡糖醇和甘露糖醇缬氨酸。这表明这两种反应有一个共同的中间体，即1-脱氧-1-(N-缬氨酰)果糖。从这些研究中我们得出结论，糖化血红蛋白A1c在β链的NH2末端具有1-脱氧-1-(N-缬氨酰)果糖。本文还讨论了糖化血红蛋白A1c可能的生物合成途径。
