Biological complexity: how cells handle glucose (Introduction)

by David Turell , Wednesday, October 17, 2018, 18:02 (2229 days ago) @ David Turell

Glucose is the primary food of life. This study shows how a series of actions by the cell controls glucose :

https://phys.org/news/2018-10-cellular-clean-up-crews-linked-body.html

" How our bodies handle glucose—the simple sugar that provides energy from the food we eat—appears to be intertwined with how cells keep themselves functioning normally, according to new University of Chicago research.

"The study, published with Scripps Research Institute scientists on Oct. 15 in Nature, found a link between the process that handles glucose in cells and the one that regulates detoxification. This suggests a new understanding of a fundamental function in our bodies, and one that may provide new insights into disorders from cancer to diabetes.

"Raymond Moellering, assistant professor in the Department of Chemistry at UChicago, was trying to tease out the role of a particular molecule involved in the pathway that triggers a cell's detoxification process—a sort of cleaning crew to remove toxins and buildups when something goes awry in the cell.

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"It appeared that the key protein to trigger this pathway, KEAP1, was being activated by a new small molecule discovered in the lab—but it didn't appear to be using any of the normal mechanisms known to scientists.

"By tracking down the pathways being affected by this molecule, Moellering's team found that it involved anotherpathway besides detoxification: the pathway that the body uses to process glucose. "Nobody knew those were directly connected," Moellering said.

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"Using a combination of techniques, they found that KEAP1 is actually triggered to action by a buildup of glucose in the cell. "It looks very clearly like KEAP1 is listening to glucose metabolism, and turning on detox mechanisms as a result," Moellering said.

"The strange part was how this happens. Researchers showed that when KEAP1 is exposed to a molecule that is produced during the breakdown of glucose, individual KEAP1 proteins join up in pairs, which then triggers a waterfall of other signals in the cell to begin detoxification mechanisms.

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"Additionally, the work shows that the cell protects itself from damage by triggering detoxification via glucose metabolism, but pushing this signal too far—as may happen in diseases like diabetes—could lead to damage that exceeds the capacity of the clean-up crew.

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"On another level, this discovery appears to establish a new category of how proteins are controlled in the body. In their quest to understand what happens every day in human cells, scientists know two major ways for proteins to go about their business. One way is for enzymes to place chemical marks on proteins, turning them off and on. The other way is for free-floating molecules in the cell to reversibly interact with proteins to control their functions. This study appears to establish a third way, which is a hybrid of the two—where these free-floating molecules directly form chemical marks on the proteins they interact with, causing specific and longer-lived effects. "Finding this kind of regulation with KEAP1 suggests it is a widespread way to control protein function," Moellering said."

Comment: Once again cellular research shows that cells function by a series of automatic reactions between special proteins, no thought processes involved. Feedback loops are always involved to control reaction limits and levels.