How may the amino acid lysine support the metabolic system? New Research

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Science 19 February 2010:

Vol. 327. no. 5968, pp. 1000 - 1004

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 M. Hancock,7 Fuchu He,3 Lunxiu Qin,5 Chin,7 Pengyuan

Yang,3 Xian Chen,3,4 Qunying Lei,1,2,8 Yue Xiong,1,2,4,{dagger} Kun-Liang

Guan1,2,8,9,{dagger}

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 s Cancer Center, University of California,

San Diego, La Jolla, CA 92093, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail:

yxiong@... (Y.X.); kuguan@... (K.L.G.)

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Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and

Metabolic Flux

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Xie, Wei Zhao, Yufeng Yao, Zhi-Bin Ning, Rong Zeng, Yue Xiong, Kun-Liang Guan,

Shimin Zhao, and Guo-Ping Zhao (19 February 2010)

Science 327 (5968), 1004. [DOI: 10.1126/science.1179687]

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Rise of the Rival.

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http://www.sciencemag.org/cgi/content/abstract/327/5968/1000

PS...yes the essential amino acid lysine is found in nutriiveda

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