New Enzyme Regulates Sugar Metabolism, Could Help Treat Obesity

Normal cells, cancer cells and yeast all need sugar to function. The findings may help explain why some tumors are more aggressive than others.

Researchers have discovered an important, previously unknown step in the metabolism of sugar that could have applications for treating obesity or type 2 diabetes down the road.

In a study published January 11 in the journal Proceedings of the National Academy of Sciences, researchers identified an enzyme present in all mammals, including humans, that prevents excessive sugar from over-accumulating in and causing damage to bodily cells. This enzyme, with the acronym G3PP (glycerol-3-phosphate phosphatase), turns a crucial by-product of glucose into glycerol, which can be excreted from the body in the urine. That stands in contrast to the majority of the other chemicals involved in the metabolic cycle, which cannot bypass the cell's lipid membrane.

It's a rare thing, at least in recent history, to describe a new metabolic enzyme that's present in all mammals and all parts of the body, says Marc Prentki, study senior author and scientist at the University of Montreal Hospital Research Center.

His team is working to find chemicals or drugs that would cause the body to produce more of this enzyme, and he hopes that a candidate could be tested in humans in the next couple of years for treating obesity and other metabolic problems.

The enzyme works by converting glycerol-3-phosphate, or Gro3P, into glycerol. Gro3P is a critical substance in bodily cells, a second-order byproduct of glucose that functions as the beginning of the glycerolipid-free fatty acid cycle, which governs how cells uses sugars and fats. By short-circuiting the beginning of this sequence, the newfound enzyme G3PP could help regulate a cycle that has become dysfunctional, as is often the case in disorders like obesity and type 2 diabetes, Prentki says.

The scientists also showed that by increasing levels of G3PP in tumor cells grown in petri dishes, they reduced the growth of these cancerous cells. G3PP "cuts down the use of glucose in [tumor] cells, which rely on glucose" to survive, says co-author and Prentki's colleague Murthy Madiraju. Finding a way to increase levels of the enzyme in tumors could be a new way to treat various cancers, he adds.