|Merrill, Jr, Alfred - BIOCHEM, SCH MED, EMORY U|
Submitted to: Asian International Toxicology Congress
Publication Type: Proceedings
Publication Acceptance Date: October 16, 1997
Publication Date: N/A
Interpretive Summary: Poisons produced by molds that can grow on certain crops such as corn, wheat or peanuts cause sickness in animals and people, and create economic losses for farmers. One group of these toxins, the fumonisins, are found almost exclusively as contaminants of corn, and are produced by a fungus that actually lives inside the corn plant. Fumonisins cause fatal diseases when inadvertently fed to horses or pigs. They have been associated with the high rate of cancer of the esophagus that occurs in certain regions of the world where corn is eaten on a daily basis. Besides the short term, toxic effects of fumonisins, it may be that exposure of some animals to low levels of the toxins over a long period of time may cause reduced ability of the animals to withstand exposure to bacteria, viruses, or other toxic agents. We have discovered the likely mechanism by which fumonisins cause toxicity. This mechanism involves the unique ability of the fumonisins to block the formation of a particular type of fat found in every cell, the sphingolipids. Sphingolipids are important constituents of cells, and help to regulate many activities of cells that are necessary for healthy bodies. This paper gives an overview of what fumonisins are, what problems they cause, and how they work.
Technical Abstract: Fumonisins are water soluble mycotoxins produced by several species of Fusarium fungi. The toxins are often found as contaminants of corn, apparently as a results of the endophytic relationship between corn and F. moniliform, i.e., the fungus lives within the tissues of the corn plant, and may actually impart some beneficial qualities to the corn, such as enhanced disease or insect resistance. Fumonisins, however, are harmful to animals that consume contaminated corn, in particular horses and swine, and may be related to the high rates of esophageal cancer that occur in some parts of the world where corn is consumed as a staple. Fumonisins are specific inhibitors of the enzyme ceramide synthase (sphinganine and sphingosine N-acyltransferase), which is a key enzyme in the pathway leading to formation of sphingomyelin and complex sphingolipids. The disruption of this pathway has several important implications for cellular function and there exists strong evidence suggesting that the toxicological properties of fumonisins are actually due to altered sphingolipid metabolism. In this paper, the nature of fumonisin toxicity, and how these effects may be related to altered signaling pathways that are mediated through sphingoid bases and their metabolites, ceramides and more complex sphingolipids will be discussed.