Regulation of cellular metabolism by protein lysine acetylation.
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.
Zhao
Shimin
S
School of Life Sciences, Fudan University, Shanghai 20032, China.
Xu
Wei
W
Jiang
Wenqing
W
Yu
Wei
W
Lin
Yan
Y
Zhang
Tengfei
T
Yao
Jun
J
Zhou
Li
L
Zeng
Yaxue
Y
Li
Hong
H
Li
Yixue
Y
Shi
Jiong
J
An
Wenlin
W
Hancock
Susan M
SM
He
Fuchu
F
Qin
Lunxiu
L
Chin
Jason
J
Yang
Pengyuan
P
Chen
Xian
X
Lei
Qunying
Q
Xiong
Yue
Y
Guan
Kun-Liang
KL
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
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