NEWS OF THE WEEK N N
CELLULAR JOY STICK BIOCHEMISTRY: Acetylation
controls much more biology than previously expected
S
CIENTISTS HAVE KNOWN for decades that
proteins can be acetylated on their lysine residues, but the modification was long seen as the poor cousin to phosphorylation, which can activate or deactivate countless processes in living cells. New research, however, reveals that acetylation is a master switch for a who’s who of cellular functions in organisms as diverse as bacteria and humans. The widespread acetylation of important proteins will likely inspire drugmakers to target enzymes that can decorate or undress proteins with acetyl groups. Acetylation is probably best known for its role in controlling which genes in a cell are put into deep storage and which ones can be accessed by transcription machinery. Hints of its versatility came last year, when researchers including Chunaram Choudhary, a biochemist at the University of Copenhagen, found that thousands of additional proteins are acetylated, including some involved in cell division and DNA repair. Now, a team including Guo-Ping Zhao of Fudan University, in Shanghai, and Kun-Liang Guan, now of the University of California, San Diego, reveals that acetylation controls glycolysis, the tricarboxylic acid and urea cycles, fatty acid metabolism, and glycogen metabolism (Science 2010, 327, 1000 and 1004).“These are the fundamental pathways in a cell—how a cell gets its energy,”
Choudhary says. Furthermore, such acetyl decorations cover the phylogenetic tree from bottom to top, he adds. “Acetylation is a very elegant and accurate way for cells to respond and adapt to the energy they have available,” Zhao explains. For example, the research team found that acetylation enables bacteria to switch between glucose and citrate energy pathways, and human liver cells to switch between glucose and amino acid ones. As researchers begin to see acetylation as a rival to phosphorylation, they will have to figure out how these two cellular control switches work in concert, Choudhary adds. Drugmakers targeting acetylation-modifying enzymes will also encounter the same difficulties they did back when they began targeting biologically important kinases and phosphatases, says Stuart L. Schreiber, a chemical biologist at the Broad Institute, in Cambridge, Mass. Merck & Co.’s vorinostat, a treatment for T-cell lymphoma and the only FDA-approved drug that targets acetylation-modifying enzymes, faced challenges because of poor selectivity, Schreiber notes. Similarly, early attempts to design drugs against phosphatases and kinases “were fraught with complicating side effects and toxicity,” he adds. Yet just as chemists have had success designing more specific drugs against phosphorylationmodifying enzymes, it might also be possible to develop drugs for specific acetylation-modifying enzymes, Schreiber says, noting his group’s discovery of the small molecule tubacin, which targets a single deacetylase.—SARAH EVERTS
NH2 N
N
HO
O O HO
OO
P
O
P
OH
OH
O
O
P
OH
O
OH
O
NH
O NH
S O
DECORATOR
Acetyl coenzyme A, which cells use to deliver acetyl groups to proteins.
CHINA’S ENVIRONMENT Unsustainable agricultural practices attract attention Focusing solely practices. Between on chemical oxygen 1981 and 2007, demand to measure China nearly tripled water pollution could its use of nitrogen be misleading, says fertilizer, according Jamie Choi, head of to a paper recently Greenpeace China’s published in Science campaign against (DOI: 10.1126/ toxic chemicals. In a science.1182570). A Chinese farmer applies nitrogen recent interview with China’s “extraorfertilizer to crops. C&EN, she said that dinarily high” rates China does not keep of nitrogen fertilizer track of the quantities of toxic substancapplication compared with Europe and es, such as mercury, that are released North America have degraded soil and eninto the environment, mostly by industry vironmental quality, the paper’s authors (C&EN, Jan. 4, page 14). write. Their survey of 154 agricultural Although it might provide an incomfields for which data from the 1980s explete picture of the extent of pollution in ist, they say, indicates a “widely occurring China, the new census brings attention to soil acidification in Chinese croplands.”— the country’s unsustainable agricultural JEAN-FRANÇOIS TREMBLAY
WWW.CEN-ONLINE.ORG
SCIENCE
China’s first national census of pollution sources reveals that agriculture plays a major role in damaging the country’s environment, according to China’s Ministry of Environmental Protection. In the past, China mostly blamed industry for its increasingly serious environmental woes. China relies primarily on chemical oxygen demand, a measure of the mass of oxygen consumed per liter of water, to quantify the level of pollution in its rivers. By that yardstick, the census found that agriculture accounted for 43% of the country’s water pollution in 2007. According to a statement released by the ministry, livestock and poultry are the main contributors of pollution from agricultural sources. Costing about $100 million and involving 570,000 workers, the census took two years to complete.
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FEBRUARY 22, 2010
