Title:
Sphingolipid metabolism: roles in signal transduction and disruption by fumonisins

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dc.contributor.author Merrill, Alfred H. en_US
dc.contributor.author Sullards, M. Cameron en_US
dc.contributor.author Wang, Elaine en_US
dc.contributor.author Voss, Kenneth A. en_US
dc.contributor.author Riley, Ronald T. en_US
dc.contributor.corporatename Georgia Institute of Technology. Dept. of Biomedical Engineering en_US
dc.contributor.corporatename Emory University. Dept. of Biomedical Engineering en_US
dc.contributor.corporatename Georgia Institute of Technology. School of Biology en_US
dc.contributor.corporatename United States. Agricultural Research Service en_US
dc.date.accessioned 2012-01-06T19:40:58Z
dc.date.available 2012-01-06T19:40:58Z
dc.date.issued 2001-05
dc.description Reproduced with permission from Environmental Health Perspectives en_US
dc.description DOI : 10.1289/ehp.01109s2283
dc.description The definitive version of this article is available at: http://dx.doi.org/10.1289/ehp.01109s2283
dc.description.abstract Sphingolipids have important roles in membrane and lipoprotein structure and in cell regulation as second messengers for growth factors, differentiation factors, cytokines, and a growing list of agonists. Bioactive sphingolipids are formed both by the turnover of complex sphingolipids and as intermediates of sphingolipid biosynthesis. Usually, the amounts are highly regulated; however, by inhibiting ceramide synthase, fumonisins block the biosynthesis of complex sphingolipids and cause sphinganine (and sometimes sphingosine) to accumulate. Where the mechanism has been studied most thoroughly, the accumulation of sphingoid bases is a primary cause of the toxicity of fumonisin B (FB). Nonetheless, the full effects of fumonisins probably involve many biochemical events. The elevations in sphingoid bases also affect the amounts of other lipids, including the 1-phosphates and N-acetyl derivatives of sphinganine. Furthermore, the aminopentol backbone of FB1 (AP1) is both an inhibitor and a substrate for ceramide synthase, and the resultant N-palmitoyl-AP1 (PAP1) is an even more potent inhibitor of ceramide synthase (presumably as a product analog). PAP1 is 10 times more toxic than FB1 or AP1 for HT-29 cells in culture, and hence may play a role in the toxicity of nixtamalized fumonisins. All these processes--the effects of fumonisins on sphingolipid metabolism, the pathways altered by perturbation of sphingolipid metabolism, and the complex cellular behaviors regulated by sphingolipids--must be borne in mind when evaluating the pathologic effects of fumonisins. en
dc.identifier.citation Merrill AH Jr, Sullards MC, Wang E, Voss KA, Riley RT 2001. Sphingolipid Metabolism: Roles in Signal Transduction and Disruption by Fumonisins. Environ Health Perspect 109:283-289. en_US
dc.identifier.doi 10.1289/ehp.01109s2283
dc.identifier.issn 0091-6765
dc.identifier.uri http://hdl.handle.net/1853/42169
dc.language.iso en_US en
dc.publisher Georgia Institute of Technology en
dc.publisher.original National Institute of Environmental Health Sciences
dc.subject Biomarker en
dc.subject C₂-ceramide en
dc.subject Ceramide synthase en
dc.subject Fumonisin B₁ en
dc.subject Lipid metabolism en
dc.subject Sphinganine en
dc.subject Sphingosine en
dc.title Sphingolipid metabolism: roles in signal transduction and disruption by fumonisins en
dc.type Text
dc.type.genre Article
dspace.entity.type Publication
local.contributor.author Merrill, Alfred H.
local.contributor.corporatename College of Sciences
local.contributor.corporatename School of Biological Sciences
relation.isAuthorOfPublication e2cc92fe-a320-49d9-a516-d6badc8d0e75
relation.isOrgUnitOfPublication 85042be6-2d68-4e07-b384-e1f908fae48a
relation.isOrgUnitOfPublication c8b3bd08-9989-40d3-afe3-e0ad8d5c72b5
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