Regulation of cellular metabolism by protein lysine acetylation.

Science 2010 Feb;327(5968):1000-4

School of Life Sciences, Fudan University, Shanghai 20032, China.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.1179689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232675PMC
February 2010
196 Reads

Publication Analysis

Top Keywords

lysine acetylation
12
urea cycle
8
protein lysine
8
tca cycle
8
fatty acid
8
acetylation
6
acids fatty
4
amino acids
4
glucose amino
4
fuels glucose
4
fatty acids
4
acids influenced
4
status metabolic
4
metabolic fuels
4
metabolic enzymes
4
influenced acetylation
4
acetylation status
4
human liver
4
acid metabolism
4
cycle fatty
4

References

(Supplied by CrossRef)

Yang et al.
Molecular cell 2008

Kim et al.
Molecular cell 2006

Science 2009

Alvares et al.
Cancer Research 1994

Yeh et al.
Cancer letters 2006

Watkins et al.
Journal of Clinical Investigation 1989

Trevisson et al.
Human mutation 2007

Jungas et al.
Physiological Reviews 1992

Lardy et al.
Current topics in cellular regulation 1984

She et al.
Molecular and Cellular Biology 2000

Molecular & Cellular Proteomics 2009

Similar Publications