Case Western Reserve and University Hospitals (UH) Case Medical Center researchers and physicians have discovered that the molecule known as coenzyme A plays a key role in cell metabolism by regulating the actions of nitric oxide (image). Cell metabolism is the ongoing process of chemical transformations within the body's cells that sustains life, and alterations in metabolism are a common cause of human disease, including cancer and heart disease. Their findings about the mechanisms of action for coenzyme A, as well as the discovery of a new class of enzymes that regulate coenzyme A-based reactions, are described in an article published online on December 15, 2015 in PNAS. "The governing role of coenzyme A in nitric oxide function was completely unknown and unanticipated before this study," said senior author Jonathan Stamler, M.D., Professor of Medicine, Case Western Reserve University (CWRU) School of Medicine, and Director, Harrington Discovery Institute at UH Case Medical Center. "Nitric oxide operates in every cell and tissue of the body to influence cell function. We are trying to work through the basic control of nitric oxide biology to elucidate the machinery underlying its mechanisms of action." Coenzyme A sets into motion a process known as protein nitrosylation, which unleashes nitric oxide to alter the shape and function of proteins within cells to modify cell behavior. The purpose of manipulating the behavior of cells is to tailor their actions to accommodate the ever-changing needs of the body's metabolism. In addition, Case Western Reserve and UH investigators identified hundreds of proteins regulated by coenzyme A-driven protein nitrosylation. Many of the newly discovered targets of nitrosylation were noted to influence cellular energy production.
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