It is not unusual to hear people blame their metabolism after gaining a few pounds. But changes in metabolism - the process that shapes how our bodies turn food into energy -- can have much more sinister effects than making it hard to fit into your favorite jeans.
In fact, differences in metabolic rates are known to exist between normal cells and tumor cells, though the mechanism behind it is unclear. Now new research from the University of North Carolina at Chapel Hill suggests that the addition or removal of a certain type of chemical tag - called an acetyl group - onto metabolic enzymes plays a key role in how cellular metabolism is regulated.
The finding, which will appear in the February 19 issue of the journal Science, gives researchers vital clues to understand how normal cells respond to nutrient changes and how the process by which normal cells turn cancerous, and could one day lead to new drugs that starve cancer cells into submission.
"We have discovered an entirely new layer of control of metabolism," said Yue Xiong, Ph.D., professor of biochemistry and biophysics and a member of the UNC Lineberger Comprehensive Cancer Center. "This process -- the acetylation of metabolic enzymes -- appears to be highly conserved during evolution and very dynamic, which makes it an ideal target for future drug development. Now if we can identify which enzyme or enzymes are responsible for the difference in metabolism between normal and tumor cells, then we could have new targets for the treating cancer patients."
Xiong is a senior author of the study along with Kun-Liang Guan, professor of pharmacology, at the University of California, San Diego.
Almost all previous studies on acetylation have focused on the proteins in the nucleus, where acetyl tags regulate how tightly the DNA's genetic code is packaged. But Xiong and Guan started this study with the hypothesis that acetylation must also play a role in the other half of the cell, the cytoplasm.
So they separated the nucleus and the cytoplasm of primary liver cells, and then took a chemical census of the cytoplasm's contents using a technology called mass spectroscopy. They identified approximately a thousand new proteins that are acetylated, greatly expanding the previously recognized repertoire of fifty.