Study shows metabolic strategy of stressed cell

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.

Metabolism is the sum of all biochemical reactions involved in maintaining the health of the cell, including breaking down and synthesizing various molecules to produce energy and build substances the cell needs to operate normally. CoA plays key roles in the cell's metabolism by participating in biochemical reactions in specific areas throughout the cell.

The St. Jude study is a significant contribution to the growing field of metabolomicsthe study of the molecules involved in metabolism. 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 with hopantenate (HoPan). HoPan is a chemical that interferes with pantothenate kinase (PanK), the enzyme that triggers the first step of 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. Mitochondria are the powerhouses of the cell, so-called because these bags of enzymes host a series of complex biochemical pathways that produce the energy-rich molecule ATPthe cell's "currency" with which it "buys" chemical reactions that consume energy.

"The cell's response to reduced CoA levels

Contact: Summer Freeman
St. Jude Children's Research Hospital

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