Role of Sugar in Cell Metabolism may Provide Clues to New Therapies

by Rajashri on Oct 21 2008 2:37 PM

Sugar plays a significant role in how cells work, Johns Hopkins scientists have found, thus paving the way for new therapies for a number of diseases like diabetes, neurodegeneration, and cancer.

The researchers say that sugar may be as influential as phosphate in putting the proteins in cells on and off.

The conventional wisdom was that the job of turning proteins on and off fell to phosphates, which did so by fastening to and unfastening from proteins, a process called phosphorylation.

The latest research paper by the Johns Hopkins team suggests that sugar also plays a role in regulating phosphorylation itself.

The team say that the new switches form yet another potential target for manipulation by drugs.

"Like dark matter in the cosmos, it's hard to find even though it's very abundant," says Dr. Gerald Hart, the DeLamar Professor and director of biological chemistry at the Johns Hopkins School of Medicine, referring to the sugar O-GlcNAc that carries out GlcNAcylation.

The researcher revealed that it was with the aid of new technologies that they could measure the extent to which the addition of sugar to proteins affects phosphorylation.

Of 428 sites on which phosphate was being added to, and taken off of proteins, all responded in some way to increased O-GlcNAc: 280 decreased phosphorylation and 148 increased phosphorylation.

"The influence of sugar is striking. The presence of O-GlcNAc causes the enzymes that add the phosphate to do something different, and this cross-talk itself can modify proteins," Hart says.

Given the association of both sugar and phosphate modifications with the working of cells, according to the researchers, they are fundamental to understanding and eventual control of the molecular processes that underlie many diseases.

"With regard to cancer, diabetes and Alzheimer's, most people in the world today have been studying the yang (phosphorylation) but not the yin (GlcNAcylation). There's another whole side that people were unaware of where diabetes diagnostics and cancer therapies could be targeted," says Hart.