University of Utah scientists may have solved an old biology riddle: How do you better understand the workings of a carbohydrate molecule critical to human health without damaging the cellular function that produces it?

Research of proteoglycans, one of the most important type of carbohydrates known as glycoconjugates, has been somewhat stymied in efforts to understand what happens inside a cell when this particular glycoconjugate isn't produced. Scientists could prevent the production of the molecule but only by using a combination of agents that are toxic to cells.

The U. College of Pharmacy has come up with a different method that doesn't harm cells and will likely allow the process to be examined in living organisms, a method that up to now would have been a waste of time.

Kuberan Balagurunathan, an assistant professor of medicinal chemistry and senior author of a paper published online last week in the Journal of Biological Chemistry, reports that his team prevented proteoglycans from being made without harming other proteins, other glycoconjugates or disrupting cell function.

"Now that we can define this molecule's role in development," he said, "we can better understand its role in the cardiovascular system, brain and other biological systems."

In what Balagurunathan described as blocking one aspect of the biological pathway "in a very mild, elegant way," the research has provided a tool to define the specific roles of the carbohydrate molecules.

The field could use a little bit of the elegant. The effort to understand their structure and function is extremely difficult, given both the enormous chemical complexity and diversity of complex carbohydrates.

There's a couple of ways in which proteoglycans are in your life, whether you're on or off potatoes at the moment: They helped guide the wiring of your brain as you grew up; they keep down the number of blood clots; chondroitin sulfate is in proteoglycans and keeps cartilage healthy in the body. In pill form, it is a widely used supplement to counter joint pain due to osteoarthritis.

These sets of molecules have such a multifaceted, complicated role in development and health that they're practically a scientific research field unto themselves. They're what hold the body together and keep bones apart. They are a source of energy — glycogen in animals and starch in plants. These molecules are also directly and widely involved in biological recognition and regulatory processes in normal growth and development, as well as in disease processes.

Another component of the proteoglycans has been linked with changes in metabolic rates, including altering sugar levels in diabetes patients, and is linked to tumor-cell growth.

The first animal model for the U. team will be zebrafish, Balagurunathan said, noting that they are excellent biological examples for studying development as well as further understanding their role in health and disease.


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