Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux

By Qijun Wang, Yakun Zhang, Chen Yang, H. Xiong, Yan Lin, Jun Yao, Hong Li, Lu Xie, Wei Zhao, Yufeng Yao and 6 more. Science, 2010

1,020 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. Reversible acetylation of metabolic enzymes helps bacteria adjust to changes in food resources. Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. We demonstrated that central metabolism enzymes in Salmonella were acetylated extensively and differentially in response to different carbon sources, concomitantly with changes in cell growth and metabolic flux. The relative activities of key enzymes controlling the direction of glycolysis versus gluconeogenesis and the branching between citrate cycle and glyoxylate bypass were all regulated by acetylation. This modulation is mainly controlled by a pair of lysine acetyltransferase and deacetylase, whose expressions are coordinated with growth status. Reversible acetylation of metabolic enzymes ensure that cells respond environmental changes via promptly sensing cellular energy status and flexibly altering reaction rates or directions. It represents a metabolic regulatory mechanism conserved from bacteria to mammals.

Subfields: Epidemiology, Geriatrics and Gerontology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ecba172c4d89880084f4491fe299a61588f302d1

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Citations in the corpus

Erasers of histone acetylation: the histone deacetylase enzymes. (2014, background): “Profiling of protein acetylation in bacteria (which do not possess histones), likewise, has indicated that HDACs deacetylate a significant number of proteins in lower organisms, emphasizing the highly conserved nature of HDACs (Wang et al. 2010).”
The Metabolic Signature of Macrophage Responses (2019, background): “Although no specific studies address the role of ACLY in regulating epigenetic changes in M1 macrophages, many enzymes and proteins are known to be affected by acetylation (83), among which NF-κB (84), IL-6, and IL-10 (85, 86).”
SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways (2013, background): “…is a major regulator of most or all metabolic pathways in amanner that is conserved from bacteria to mammals (Finley et al., 2011; Hallows et al., 2011; Hebert et al., 2013; Hirschey et al., 2011; Smith et al., 2011; Starai et al., 2002; Wang et al., 2010; Zhang et al., 2009; Zhao et al., 2010).”
SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks (2013, neutral): “In prokaryotes and eukaryotes, acetylation regulates the functions of many metabolic enzymes (Wang et al., 2010; Zhao et al., 2010).”
Cyclic AMP Signaling in Mycobacteria (2014, background): “In E. coli and Salmonella, acetylation of proteins is altered in response to carbon source availability, leading to differences in carbon and energy source usage and changing the metabolism of fatty acids and nucleotides (79 – 82).”
Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013, background): “metabolic enzymes (49, 50), reinforcing metabolic pathways such as glycolysis when carbon”
Acetyl-CoA Induces Cell Growth and Proliferation by Promoting the Acetylation of Histones at Growth Genes (2011, background): “As protein acetylation has also been linked to metabolism in several previous studies (Choudhary et al., 2009; Friis et al., 2009; Takahashi et al., 2006; Wang et al., 2010; Wellen et al., 2009; Zhao et al., 2010), we predict that a similar control of gene expression and protein activities with resp”
SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate the Development of the Metabolic Syndrome (2011, neutral): “…proteomics analyses revealed that every major metabolic pathway contains acetylated proteins, including glycolysis, the tricarboxylic acid (TCA) cycle, the urea cycle, fatty acid metabolism, and glycogen metabolism (Choudhary et al., 2009; Kim et al., 2006; Wang et al., 2010; Zhao et al., 2010).”
Post-translational modifications in signal integration (2010, background): “Two remarkable proteomic studies have identified the acetylation of lysine as a dominant PTM in almost all intermediary metabolism enzymes of glycolysis, gluconeogenesis and the tricarboxylic acid cycle by MS approache”
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”