|Merrill Jr, Alfred - BIOCHEM, EMORY UNIV|
|Wang, Elaine - BIOCHEM, EMORY UNIV|
|Vales, T - BIOCHEM, EMORY UNIV|
|Smith, E - BIOCHEM, EMORY UNIV|
|Schroeder, J - BIOCHEM, EMORY UNIV|
|Menaldino, D - CHEMISTRY, EMORY UNIV|
|Alexander, C - CHEM, EMORY UNIV|
|Crane, H - CHEM, EMORY UNIV|
Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: June 28, 1996
Publication Date: N/A
Interpretive Summary: Fumonisins are toxic chemicals produced by molds which are present on corn. They are toxic to animals, plants, and other molds. The fumonisins are unique in that they prevent the formation of a gorup of fats known as sphingolipids. One result of the effect on sphingolipid formation is that fat normally present in plants and animals in very small amounts becomes greatly elevated. Once elevated this fat (sphinganine) is chemically modified to another compound which contains a molecule of phosphate. This new phosphate containing compound also becomes greatly elevated and is chemically modified so that eventually another fat is made which also becomes elevated. All of these fats which become elevated are capable of changing the way cells in animals and plants behave. Attempts to reduce the adverse effects of fumonisins in animals and plants will require that the changes in fat metabolism be prevented or reduced.
Technical Abstract: Fumonisins are inhibitors of sphinganine (sphingosine) N-acyltransferase (ceramide synthase) in vitro, and exhibit competitive-type inhibition with respect to both substrates of this enzyme (sphinganine and fatty acyl-CoA). Removal of the tricarballylic acids from fumonisin B1 reduces the potency by at least 10 fold; and fumonisin A1 (which is acetylated on the amino group) is essentially inactive. Studies with diverse types of cells (hepatocytes, neurons, kidney cells, fibroblasts, macrophages, and plant cells) have established that fumonisin B1 not only blocks the biosynthesis of complex sphingolipids; but also, causes sphinganine to accumulate. Some of the sphinganine is metabolized to the 1-phosphate and degraded to hexadecanal and ethanolamine phosphate, which is incorporated into phosphatidylethanolamine. Sphinganine is also released from cells and, because it appears in blood and urine, can be used as a biomarker for exposure. The accumulation of these bioactive compounds, as well as the depletion of complex sphingolipids, may account for the toxicity, and perhaps the carcinogenicity, of fumonisins.