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Fumonisin toxicity and sphingolipid biosynthesis
A H Merrill1, E Wang, T R Vales
1Department of Biochemistry, Emory University, Atlanta, GA 30322, USA.
Advances in Experimental Medicine and Biology
|January 1, 1996
Summary
Fumonisins inhibit sphingolipid biosynthesis by blocking ceramide synthase. This leads to toxic sphinganine accumulation, which can be detected in blood and urine as a biomarker for exposure.
Area of Science:
- Biochemistry
- Toxicology
- Cell Biology
Background:
- Fumonisins are mycotoxins that inhibit sphingolipid biosynthesis.
- They act as competitive inhibitors of sphinganine (sphingosine) N-acyltransferase (ceramide synthase).
- Structural modifications, like removal of tricarballylic acids or acetylation, significantly alter fumonisin potency and activity.
Purpose of the Study:
- To investigate the biochemical mechanism of fumonisin toxicity.
- To understand the cellular consequences of fumonisin exposure.
- To identify potential biomarkers for fumonisin exposure.
Main Methods:
- In vitro enzyme inhibition assays using sphinganine and fatty acyl-CoA substrates.
- Cell-based studies using various cell types (hepatocytes, neurons, kidney cells, fibroblasts, macrophages, plant cells).
- Analysis of sphingolipid metabolism and accumulation of metabolites.
Main Results:
- Fumonisin B1 was confirmed as a potent inhibitor of ceramide synthase.
- Cellular studies showed fumonisin B1 blocks complex sphingolipid biosynthesis and causes sphinganine accumulation.
- Accumulated sphinganine is metabolized and also released from cells, appearing in blood and urine.
Conclusions:
- Fumonisins disrupt sphingolipid metabolism by inhibiting ceramide synthase.
- Accumulation of sphinganine and depletion of complex sphingolipids contribute to fumonisin toxicity and potential carcinogenicity.
- Sphinganine in blood and urine serves as a reliable biomarker for fumonisin exposure.