Regulation of Cellular Metabolism by Protein Lysine Acetylation
By Shimin Zhao, W. Xu, Wenqing Jiang, Wei Yu, Yan Lin, Tengfei Zhang, Jun Yao, Li Zhou, Yaxue Zeng, Hong Li and 12 more. Science, 2010
1,880 citations recorded by the source corpus.
Metabolic Regulation Through Acetylation Covalent modification of lysine residues in various proteins in the nucleus is a recognized mechanism for control of transcription. Now two papers suggest that acetylation may represent an important regulatory mechanism controlling the function of metabolic enzymes (see the Perspective by Norvell and McMahon). Zhao et al. (p. 1000) found that a large proportion of enzymes in various metabolic pathways were acetylated in human liver cells. Acetylation regulated various enzymes by distinct mechanisms, directly activating some, inhibiting one, and controlling the stability of another. Control of metabolism by acetylation appears to be evolutionarily conserved: Wang et al. (p. 1004) found that the ability of the bacterium Salmonella entericum to optimize growth on distinct carbon sources required differential acetylation of key metabolic enzymes, thus controlling flux through metabolic pathways. Regulation of enzymes by acetylation controls metabolic function in human liver cells. 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.
Subfields: Geriatrics and Gerontology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/16bc36438dfcfe6c602571eeec088b46dcb732e3
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In Geriatrics and Gerontology
In Molecular Biology
Citations in the corpus
- Glycogen and its metabolism: some new developments and old themes. (2012, background): “[112] reported on a proteomic analysis of the acetylation of lysine residues in human liver proteins.”
- Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. (2013, background): “We found that succinylation occurred at many sites that were previously shown to be regulated by acetylation, including homologous lysines 172, 344, and 579 on 3,2-trans-enoyl-CoA isomerase,3-hydroxyacyl-CoA dehydrogenase (EHHADH) and malate dehydrogenase 2 (MDH2) lysines 185, 301, 307, and 314 (Zha”
- Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “In addition, the activities of many metabolic enzymes are regulated by acetylation modulation (Choudhary et al., 2009; Zhao et al., 2010).”
- Sirtuin Regulation of Mitochondria - Energy Production, Apoptosis, and Signaling (2010, background): “Furthermore, a growing body of mass spectrometry data demonstrates that numerous mitochondrial proteins involved in metabolism and stress are acetylated [35-37], hinting that sirtuins might regulate a broad range of mitochondrial biology, including energy production, signaling, and apoptosis.”
- Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes (2011, background): “1759" language="eng" relation="no"> Protein lysine acetylation is a key mechanism in the epigenetic control of gene expression and the regulation of cell metabolis”
- Cardiac Metabolism and Its Interactions with Contraction, Growth, and Survival of the Cardiomyocte (2013, background): “Increased glucose metabolism also elevates the citrate level in the cytosol, providing more acetyl-CoA for the acetylation of proteins.(100,101) It remains to be determined whether these changes contribute to the maladaptive nature of increased glucose use in heart failure.”
- Myelination and support of axonal integrity by glia (2010, background): “Recent reports that acetylation regulates the key steps of intermediate metabolis”
- Energy Metabolism in the Liver (2014, positive): “Most liver enzymes, which regulate glycolysis, gluconeogenesis, the TCA cycle, the urea cycle, and fatty acid and glycogen metabolism, are acetylated, and acetylation levels are regulated by nutrient availability (303).”
- The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? (2016, background): “, 2016), rivalling the much longer-known regulation of proteins by phosphorylation (Norvell and McMahon, 2010; Zhao et al., 2010).”
- SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate the Development of the Metabolic Syndrome (2011, positive): “Acetylation controls the enzymatic activity of mitochondrial metabolic enzymes such as malate dehydrogenase in the TCA cycle (Zhao et al., 2010), enoyl-coA hydratase/3-hydroxyacyl-coA dehydrogenase (Zhao et al., 2010), and long-chain acyl-CoA dehydrogenase (LCAD) (Hirschey et al., 2010) in the…”
- Decoding signalling networks by mass spectrometry-based proteomics (2010, background): “Lys acetylation also seems to have a previously unappreciated role in regulating metabolic pathways in human liver and Salmonella enteric”