人體80%疾病與代謝有關(guān),，揭開代謝的奧秘就等于找到了制服疾病的密鑰,。2月19日出版的國際權(quán)威刊物《科學(xué)》同時刊發(fā)了兩篇復(fù)旦大學(xué)科研人員對生命新陳代謝乙酰化作用新機制的最新研究成果,。兩篇題為《代謝酶的乙?；瘏f(xié)調(diào)碳源的利用和代謝》和《蛋白賴氨酸的乙酰化調(diào)控》文章，以蛋白質(zhì)向能量轉(zhuǎn)化過程中“乙?；揎?rdquo;的重要發(fā)現(xiàn),，為肝病、腫瘤等代謝疾病的藥物研發(fā)提供了開拓性的思路,。
 
最新的研究成果來自于復(fù)旦大學(xué)生物醫(yī)學(xué)研究院分子細胞生物學(xué)研究室趙世民和雷群英團隊,。據(jù)介紹，構(gòu)成人體最基本結(jié)構(gòu)與功能的單位是細胞,細胞主要通過蛋白質(zhì)執(zhí)行復(fù)雜的調(diào)控和信息傳遞功能,。而在執(zhí)行前,，往往需要先在蛋白質(zhì)分子鏈上接上某種分子或分子團，稱為蛋白質(zhì)的修飾,。“乙?；揎?rdquo;——即在蛋白質(zhì)分子鏈上嫁接上一個乙酰基分子是蛋白質(zhì)最主要的修飾方式之一,。修飾后的蛋白質(zhì)可以對細胞內(nèi)的各類通路進行精確的調(diào)節(jié)與控制,，完成對基因所發(fā)出的“指令”的執(zhí)行過程。揭開蛋白質(zhì)“乙?；揎?rdquo;的機理之謎,，將為破解蛋白質(zhì)修飾規(guī)律的生命之謎打下重要基礎(chǔ)。
 
科學(xué)界早期一般認(rèn)為,，乙?；揎椆δ苤饕性趯毎旧w結(jié)構(gòu)的影響以及對核內(nèi)轉(zhuǎn)錄調(diào)控因子的激活方面。但是,，復(fù)旦科研人員通過通量化的蛋白質(zhì)組研究和不同物種的代謝通路研究發(fā)現(xiàn),，在生理狀況下，存在著大量非細胞核的蛋白被乙?；揎?，而且在從低等原核生物到包括人在內(nèi)的高等哺乳動物，乙?；瘜Υx的調(diào)控,，不僅普遍存在著，而且在生命進化過程中一直保存下來,。
 
鑒于現(xiàn)在人體80%疾病與代謝有關(guān),，《科學(xué)》雜志的評論認(rèn)為：該研究為開發(fā)調(diào)控代謝的藥物提供了新的思路，為包括腫瘤在內(nèi)的新的治療手段的發(fā)展提供了可能,。（生物谷Bioon.com）

生物谷推薦原文閱讀：

Science 19 February 2010 | DOI: 10.1126/science.1179689

Regulation of Cellular Metabolism by Protein Lysine Acetylation
Shimin Zhao,1,2 Wei Xu,1,2,* Wenqing Jiang,1,2,* Wei Yu,1,2 Yan Lin,2 Tengfei Zhang,1,2 Jun Yao,3 Li Zhou,4 Yaxue Zeng,4 Hong Li,5 Yixue Li,6 Jiong Shi,6 Wenlin An,7 Susan M. Hancock,7 Fuchu He,3 Lunxiu Qin,5 Jason Chin,7 Pengyuan Yang,3 Xian Chen,3,4 Qunying Lei,1,2,8 Yue Xiong,1,2,4, Kun-Liang Guan1,2,8,9,

Protein lysine acetylation has emerged as a key posttranslational modification in cellular regulation, in particular through the modification of histones and nuclear transcription regulators. We show that lysine acetylation is a prevalent modification in enzymes that catalyze intermediate metabolism. Virtually every enzyme in glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, the urea cycle, fatty acid metabolism, and glycogen metabolism was found to be acetylated in human liver tissue. The concentration of metabolic fuels, such as glucose, amino acids, and fatty acids, influenced the acetylation status of metabolic enzymes. Acetylation activated enoyl–coenzyme A hydratase/3-hydroxyacyl–coenzyme A dehydrogenase in fatty acid oxidation and malate dehydrogenase in the TCA cycle, inhibited argininosuccinate lyase in the urea cycle, and destabilized phosphoenolpyruvate carboxykinase in gluconeogenesis. Our study reveals that acetylation plays a major role in metabolic regulation.

1 School of Life Sciences, Fudan University, Shanghai 20032, China.
2 Molecular and Cell Biology Lab, Fudan University, Shanghai 20032, China.
3 Center of Proteomics, Institute of Biomedical Sciences, Fudan University, Shanghai 20032, China.
4 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
5 Affiliated Zhongshan Hospital, Fudan University, Shanghai 20032, China.
6 Bioinformatics Center, Key Lab of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
7 Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 OQH, UK.
8 Department of Biological Chemistry, Fudan University, Shanghai 20032, China.
9 Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.

Science 19 February 2010 | DOI: 10.1126/science.1179687

Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux
Qijun Wang,1 Yakun Zhang,2 Chen Yang,3 Hui Xiong,1,2 Yan Lin,4 Jun Yao,4 Hong Li,3 Lu Xie,3 Wei Zhao,3 Yufeng Yao,5 Zhi-Bin Ning,3 Rong Zeng,3 Yue Xiong,4,6 Kun-Liang Guan,4,7 Shimin Zhao,1,4,* Guo-Ping Zhao1,2,3,8,*

Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. We demonstrated that central metabolism enzymes in Salmonella were acetylated extensively and differentially in response to different carbon sources, concomitantly with changes in cell growth and metabolic flux. The relative activities of key enzymes controlling the direction of glycolysis versus gluconeogenesis and the branching between citrate cycle and glyoxylate bypass were all regulated by acetylation. This modulation is mainly controlled by a pair of lysine acetyltransferase and deacetylase, whose expressions are coordinated with growth status. Reversible acetylation of metabolic enzymes ensure that cells respond environmental changes via promptly sensing cellular energy status and flexibly altering reaction rates or directions. It represents a metabolic regulatory mechanism conserved from bacteria to mammals.

1 State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences and Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
2 MOST-Shanghai Laboratory of Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, China.
3 Key Laboratory of Synthetic Biology, Bioinformatics Center and Laboratory of Systems Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
4 Molecular Cell Biology Laboratory, Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
5 Laboratory of Human Bacterial Pathogenesis, Department of Medical Microbiology and Parasitology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
6 Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
7 Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
8 Department of Microbiology and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.