Mechanism of action of sphingolipids and their metabolites in the toxicity of fumonisin B1

Abstract

Fumonisins are a group of mycotoxins produced primarily by Fusarium moniliforme. Several fumonisins have been isolated through out the years but only fumonisin B1, B2 and B3 are the ones present in naturally contaminated foods, with B1 being the most toxic between them. The structural similarity between sphinganine and fumonisin B1 suggests that the mechanism of action of this mycotoxin is mainly via disruption of sphingolipid metabolism, this is an important step in the cascade of events leading to altered cell growth, differentiation and cell injury. Sphingolipids are a second type of lipid found in cell membranes, particularly nerve cells and brain tissues. Toxicity of fumonisin B1 is given via inhibition of ceramide synthase that catalyzes the formation of dihydroceramide from sphingosine. This mechanism of action may explain the wide variety of health effects observed when this mycotoxin is ingested like high rate of human oesophageal cancer and promotion of primary liver cancer.