Exactly how cells function has long puzzled biologists, preventing them from fully understanding and treating various metabolic conditions and diseases.

But a University of Pittsburgh study has outlined the structure and function of an enzyme that plays a critical role in glycerol metabolism, providing a scientific foundation for new treatments for diabetes, obesity, heart disease and other chronic disorders. It also provides fresh insights into longevity and aging.

Joanne I. Yeh, a structural biologist with the University of Pittsburgh School of Medicine, is the first to decipher the three-dimensional structure of the enzyme Sn-glycerol-3-phosphate dehydrogenase.

Call it GlpD.

The enzyme, bound to cell membranes in humans and most organisms, plays a key role in metabolizing glycerol, an essential source of energy that helps drive cellular respiration -- the oxidation of food molecules such as glucose and fatty acids into carbon dioxide and water.

"This enzyme is the machine in the body that specifically functions to make the molecules used in fatty-acid and carbohydrate metabolism," Dr. Yeh said. "It is important because it regulates the metabolic process."

Her study is published in the March 4 issue of Proceedings of the National Academy of Sciences.

Dr. Yeh and her team of researchers separated the GlpD enzyme from the cell membrane while preserving its structure, then crystallized it for analysis in Pitt's X-ray crystallography facility.

X-ray analysis, and use of particle accelerators at the Argonne National Laboratory in Illinois and the Paul Scherrer Institut in Switzerland, helped determine the protein's atomic configuration. Then the team used computers and complex mathematics to decipher the enzyme crystals, atom by atom.

The result is "the highest resolution structure" to date of this class of enzymes embedded in cell membranes.

The complicated science of GlpD involves various enzymes, proteins and biological reactions. Outlining how the enzyme strongly influences metabolism represents a breakthrough likely to lead to new treatments for diabetes, liver disease and other metabolic ailments, Dr. Yeh said.

GlpD also determines whether the body converts glycerol into energy for immediate use or sends it into fat storage, which sheds new light on obesity and longevity.

Dr. Yeh said she started studying glycerol metabolism after receiving her doctoral degree, but long before it was on most people's radar.

"Glycerol metabolism has long-reaching influence on cellular processes, including energy production," she said, noting her current research into how mutations of certain amino acids in the enzyme affect its function and structure.

The National Institutes of Health funded the research, with support from the U.S. Department of Energy's Office of Basic Energy Sciences.