Author
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Riley, Ronald |
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Submitted to: World Health Organization
Publication Type: Other Publication Acceptance Date: 2/20/2002 Publication Date: N/A Citation: N/A Interpretive Summary: No Interpretive Summary required for a monograph. Technical Abstract: Fumonisin-induced disruption of lipid metabolism is observed both in vitro and in vivo. Biochemical consequences of fumonisin-disruption of sphingolipid metabolism most likely to alter cell regulation are increased free sphingoid bases and their 1-phosphates, alterations in complex sphingolipids, and decreased ceramide biosynthesis. Because free sphingoid bases and ceramide can induce cell death, fumonisin inhibition of ceramide synthase can inhibit cell death induced by ceramide, but can promote free sphingoid base-induced cell death. Kinetics of increases and decreases in various bioactive sphingolipid pools in liver, kidney, lung and heart will also be important factors in the observed toxicity. Fumonisins also induced a myriad of changes in fatty acids and phospholipids in primary rat hepatocytes and rat liver in vivo. Changes closely reflect those expected with disruption of the delta 6 desaturase enzyme, the rate-limiting enzyme in fatty acid metabolism and disruption of prostaglandin biosynthesis. Changes in fatty acid and phospholipid metabolism most likely to alter cell regulation are: changes in the degree of saturation of fatty acids within the phospholipid pools, increase in the ratio of phosphatidyl- choline to phosphatidylethanola-mine, changes in prostaglandin biosynthesis, and altered ceramide production. Fumonisins also affect other sites of cellular regulation that are independent of the disruption of lipid metabolism. However, disruption of various aspects of lipid metabolism, membrane structure and signal transduction pathways mediated by lipid second messengers appears to be an important aspect of all the various proposed mechanisms of action. |
