Investigators at St. Jude Children's Research Hospital have mapped out many of the dynamic genetic and biochemical changes that make up a cell's response to a shortage of a molecule called Coenzyme A (CoA), a key player in metabolism.
The results provide the most detailed look ever obtained of the complex metabolic changes in a cell triggered by a potentially fatal stress. CoA plays key roles in the cell's metabolism by participating in biochemical reactions in specific areas throughout the cell.
"The study provides the first detailed look at how the cell shifts genetic gears to respond to a significant change in its ability to carry on its daily metabolic chores," said Suzanne Jackowski, Ph.D., a member of the St. Jude Infectious Diseases department and the paper's senior author.
The St. Jude study is a significant contribution to the growing field of metabolomics -- the study of the molecules involved in metabolism, added Charles Rock, Ph.D., a member of the St. Jude Infectious Diseases department and co-author of the paper.
Coupled with genetic studies of the cell, metabolomics is giving scientists a more detailed picture of how the body maintains its health in both normal environments and during times of stress, such as starvation or disease.
A report on this work appears in the March issue of "Chemistry and Biology."
The researchers studied the response to decreased CoA in a mouse model by blocking CoA production. Following the shutdown of CoA production, the cells quickly recycled CoA from other jobs so it could concentrate all its efforts on a single task: extracting life-supporting energy from nutrients in the mitochondria-the powerhouses of the cell.
"We identified the metabolic rearrangements the cell undergoes to ensure that the liver keeps CoA levels high enough to produce glucose and the cells of the body maintain enough free CoA for the mitochondria to keep producing ATP," said Yong-Mei Zhang, Ph.D., of the St. Jude Infectious Diseases department and first author of the report.
Other authors of this paper include Shigeru Chohnan (St. Jude), Kristopher G. Virga and Richard E. Lee (University of Tennessee Health Science Center, Memphis, Tenn.); Robert D. Stevens, Olga R. Ilkayeva, Bret R. Wenner, James R. Bain and Christopher B. Newgard (Duke University Medical Center, Durham, N.C.).