A new category of fats in mammalian cells discovered by Agricultural Research Service (ARS) scientists and colleagues may help explain how a harmful toxin called fumonisin causes disease in farm animals.
The discovery could open up a new research area for exploring ways to reduce the toxic effects of fumonisin, which is found in corn that has been infected with a fungus called Fusarium. Fumonisin is known to cause a host of diseases, such as equine leukoencephalomalacia, which is a brain disease in horses, and porcine pulmonary edema, a lung disease in swine.
In previous work, these scientists found that fumonisin inhibits the formation of a group of fats known as sphingolipids and disrupts the metabolism of sphingolipids and other fats. It is now known that this disruption of fat metabolism is the cause of the animal diseases and also kidney and liver toxicity and cancer in rodent animal models. In the earlier studies, this group showed that inhibition increases the levels of several well-known sphingolipid metabolites and an unidentified sphingolipid which was coined "the mystery peak."
ARS toxicologist Ronald Riley at the ARS Richard B. Russell Research Center in Athens, Ga., and colleagues at Health Canada in Ottawa, Emory University in Atlanta, Ga., and the Georgia Institute of Technology in Atlanta identified the "mystery" compound. The research was published recently in the Journal of Biological Chemistry.
Riley and his colleagues found that the first enzyme that makes the backbone--sphinganine--common to all sphingolipids normally uses serine as a substrate. However, the mystery compound was being produced because the enzyme was using the amino acid "alanine" instead.
This is important because the oxygen atom which is found on serine is critical in the formation of more complex sphingolipids. Thus, this new sphingoid base was called 1-deoxysphinganine and serves as the backbone for a new category of sphingolipids (1-deoxydihydroceramides) in mammalian cells and tissues.
This new sphingoid base accumulates in cells and tissues after fumonisin exposure. Riley and his colleagues showed that the amount of 1-deoxysphinganine rises when levels of serine fall relative to alanine. Thus, these compounds are an underappreciated category of bioactive sphingolipids that might play important roles in cell regulation and disease.
ARS is the primary intramural scientific research agency in the U.S. Department of Agriculture.