New Modes of GPCR Signalling

ABSTRACT
Regulation of Cellular Metabolism by Protein Lysine Acetylation
Shimin Zhao, Wei Xu , Wenqing Jiang, Wei Yu, Yan Lin, Tengfei Zhang, Qunying Lei,
Yue Xiong and Kun-Liang Guan
Molecular and Cell Biology Laboratory, Institute of Biomedical Sciences, Fudan
University, Shanghai 20032, China
Protein lysine acetylation has emerged as a key posttranslational modification in cellular
regulation, in particular through 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, tricarboxylic acid (TCA) cycle, urea cycle, fatty acid metabolism, and
glycogen metabolism was acetylated in human liver tissue. The concentration of
metabolic fuels, such as glucose, amino acids, and fatty acids, influenced acetylation
status of metabolic enzymes. Acetylation activated enoyl-Coenzyme A
hydratase/3-hydroxyacyl-Coenzyme A dehydrogenase (EHHADH) in fatty acid
oxidation and malate dehydrogenase (MDH) in the TCA cycle, inhibited
argininosuccinate lyase (ASL) in the urea cycle, and destabilized phosphoenolpyruvate
carboxykinase (PEPCK) in gluconeogenesis. Our study reveals that acetylation plays
a major role in metabolic regulation.