title: Regulation of cellular metabolism by protein lysine acetylation.
abstract: 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.
authors.affiliation: School of Life Sciences, Fudan University, Shanghai 20032, China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Wenqing
authors.initials: W
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Tengfei
authors.initials: T
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Yaxue
authors.initials: Y
authors.lastname: Zeng
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.forename: Jiong
authors.initials: J
authors.lastname: Shi
authors.forename: Wenlin
authors.initials: W
authors.lastname: An
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hancock
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Lunxiu
authors.initials: L
authors.lastname: Qin
authors.forename: Jason
authors.initials: J
authors.lastname: Chin
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Yang
authors.forename: Xian
authors.initials: X
authors.lastname: Chen
authors.forename: Qunying
authors.initials: Q
authors.lastname: Lei
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiong
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000107:Acetylation; D001123:Argininosuccinate Lyase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002952:Citric Acid Cycle; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005943:Gluconeogenesis; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007535:Isomerases / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D010084:Oxidation-Reduction; D063994:Peroxisomal Bifunctional Enzyme; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D020543:Proteome; D014508:Urea / Q000378:metabolism
chemical_list: D004798:Enzymes; D005227:Fatty Acids; D047908:Intracellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D011506:Proteins; D020543:Proteome; D014508:Urea; D006003:Glycogen; D015094:3-Hydroxyacyl CoA Dehydrogenases; D008291:Malate Dehydrogenase; C521898:PCK1 protein, human; D010729:Phosphoenolpyruvate Carboxykinase (GTP); C576253:EHHADH protein, human; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D001123:Argininosuccinate Lyase; D007535:Isomerases; D008239:Lysine