Enzymes play critical roles in our metabolism; one in particular, phosphatidic acid phosphatase, is known as an important regulator of fat in the human body. If we are to fight obesity successfully, it is vital to understand more about the function of this enzyme. New work from researchers at Rutgers University-New Brunswick has indicated that eliminating this enzyme can cause an increase in susceptibility to cancer and inflammation, which underlies many diseases. This research has been reported in the Journal of Biological Chemistry.
"The goal of our lab is to understand how we can tweak and control this enzyme," said George M. Carman, Board of Governors Professor in the Department of Food Science in the School of Environmental and Biological Sciences. "For years, we have been trying to find out how to fine-tune the enzyme's activity so it's not too active, and creating too much fat, but it's active enough to keep the body healthy." Learn more about the work from the video.
After the enzyme was discovered in 1957, the gene that encodes for phosphatidic acid phosphatase was identified in 2006 by Gil-Soo Han, a Research Assistant Professor in the Rutgers Center for Lipid Research. It controls whether phosphatidic acid in the body is utilized for making fat, or for the creation of lipids that make up cell membranes. After the gene was found, investigators have tried to elucidate how it plays a role in disease states like diabetes, lipodystrophy, obesity, and inflammation, among other disorders, said Carman.
For this work, baker’s yeast was used as a model because it carries the enzyme. Han, who was the lead author of the report, eliminated a gene in the yeast to remove the enzyme. The scientists then saw that phosphatic acid accumulated and cells began to make too many membrane lipids, more than was necessary, explained Carman.
"We have found that (maybe) a more critical role for the enzyme is to make sure that cells are not making too much membrane lipid," suggested Carman, who founded the center in Rutgers' New Jersey Institute for Food, Nutrition, and Health. "If you make too much membrane lipid, you make too much membrane, and the cells are permitted to grow uncontrollably, a condition characteristic of cancer."
The Rutgers scientists have been building on this work; they are now investigating the structure and function of the enzyme. The next goal is to determine out how to manipulate it, Carman said. "The key take-home message is that things have to be balanced," he noted. "To keep the balance between making storage fat and membrane lipid, you have to have balanced diet."