2015年1月15日訊 /生物谷BIOON/ --隨著人們生活水平的提高，糖尿病已經成為所有人不得不正視的問題。然而，經過這麼多年的研究，科學家尚未能徹底了解清楚糖尿病的完整機理。
2015年1月1日，中科院楊福愉、楊福全等人發布在Molecular & Cellular Proteomics發表了題為「Lysine malonylation is elevated in type 2 diabetic mouse models and enriched in metabolic associated proteins.」的研究結果，揭示了蛋白質丙二醯化修飾與2型糖尿病發生發展的相關性。
研究人員通過檢測2型糖尿病小鼠模型的多種蛋白質醯基化修飾，發現：
•發生於賴氨酸殘基的丙二醯化修飾在2型糖尿病小鼠肝臟組織中明顯高於對照組小鼠，而其它醯基化修飾沒有明顯變化，提示丙二醯化修飾可能與2型糖尿病相關。
•隨後研究人員分別在2型糖尿病和對照小鼠肝臟組織中鑑定出了200餘種發生丙二醯化修飾的蛋白質，並發現在2型糖尿病小鼠肝臟組織中發生丙二醯化修飾的蛋白質和修飾位點的數量都明顯高於對照小鼠。
•生物信息學分析表明發生丙二醯化修飾的蛋白質中約有70%與糖、脂等的代謝途徑密切相關，且50%以上定位於線粒體；酶反應動力學實驗表明丙二醯化修飾可顯著影響關鍵代謝酶的活性。
以上結果將蛋白質的丙二醯化修飾與2型糖尿病聯繫起來，並提示2型糖尿病的糖脂代謝紊亂可能與關鍵酶發生翻譯後修飾、導致功能失調有關。為今後更好的認識糖尿病的致病機理做出了貢獻。
關於蛋白質醯基化修飾
蛋白質醯基化修飾（acylation）是一類特別的蛋白質翻譯後修飾，其修飾基團的供體是代謝途徑的中間產物，如乙醯化修飾的乙醯基由乙醯輔酶A提供。除乙醯化修飾外，近年還鑑定出了一系列新型的醯基化修飾，包括丙醯化（propionylation）、丁醯化（butyrylation）、琥珀醯化（succinylation）、豆蔻醯化（crotonylation）、丙二醯化（malonylation）等。
但這些新型醯基化修飾對蛋白質結構與功能的調控作用尚不清楚，其與重大疾病的發生發展是否具有相關性是亟待解決的問題。（生物谷Bioon.com）
生物谷推薦的英文摘要：
Molecular & Cellular Proteomics
doi: 10.1074/mcp.M114.041947.
Lysine Malonylation Is Elevated in Type 2 Diabetic Mouse Models and Enriched in Metabolic Associated Proteins
Yipeng Du, Tanxi Cai, Tingting Li, Peng Xue, Bo Zhou, Xiaolong He, Peng Wei, Pingsheng Liu, Fuquan Yang and Taotao Wei
Protein lysine malonylation, a newly identified protein post-translational modification (PTM), has been proved to be evolutionarily conserved and is present in both eukaryotic and prokaryotic cells. However, its potential roles associated with human diseases remain largely unknown. In the present study, we observed an elevated lysine malonylation in a screening of seven lysine acylations in liver tissues of db/db mice, which is a typical model of type 2 diabetes. We also detected an elevated lysine malonylation in ob/ob mice, which is another model of type 2 diabetes. We then performed affinity enrichment coupled with proteomic analysis on liver tissues of both wild-type (wt) and db/db mice and identified a total of 573 malonylated lysine sites from 268 proteins. There were more malonylated lysine sites and proteins in db/db than in wt mice. Five proteins with elevated malonylation were verified by immunoprecipitation coupled with Western blot analysis. Bioinformatic analysis of the proteomic results revealed the enrichment of malonylated proteins in metabolic pathways, especially those involved in glucose and fatty acid metabolism. In addition, the biological role of lysine malonylation was validated in an enzyme of the glycolysis pathway. Together, our findings support a potential role of protein lysine malonylation in type 2 diabetes with possible implications for its therapy in the future.