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Title: ALTERATION IN SPHINGOLIPID METABOLISM: BIOASSAY FOR FUMONISIN- AND ISP-I-LIKE ACTIVITY IN TISSUES, CELLS, AND OTHER MATRICES

Author
item Riley, Ronald
item Norred, William
item WANG, E - BIOCHEM/EMORY U., ATLANTA
item MERRILL, JR, A - BIOCHEM/EMORY U., ATLANTA

Submitted to: Natural Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/20/2000
Publication Date: 12/15/2000
Citation: N/A

Interpretive Summary: Fumonisin B1 is a toxic chemical that was the first discovered naturally occurring blocker of a step (ceramide synthase) in the pathway for making a unique class of fats known as sphingolipids. There are now 11 identified blockers of ceramide synthase (CS) made by fungi. We call these blockers "fumonisin-like" compounds. Most of the fumonisin-like blockers are structurally similar to sphingolipids. There are also several fungal blockers of another step in the pathway for making sphingolipids. This step is called serine palmitoyltransferase (SPTase). One of the SPTase blockers is named ISP-I and in this paper we have defined all fungal SPTase blockers as being "ISP-I-like". While CS blockers are toxic to animals, plants, and fungi, the SPTase blockers are not known to cause farm animal or plant disease, but are potent inhibitors of fungal growth. Very little is known about their toxicity in animals. There are at least 24 fungal SPTase blockers produced by a variety of fungi. Given that the fungal blockers of sphingolipid biosynthesis are chemically and biologically diverse, two bioassays have been developed to screen for fumonisin-like or ISP-I-like activity in tissues, plant products, or fungal culture materials. These bioassays are based on the changes in concentration of certain sphingolipids that occur when the steps are blocked. The bioassays have the advantage that they are functionally rather than chemically specific and thus will detect CS and SPTase blockers regardless of their chemical structure.

Technical Abstract: The first discovered naturally occurring inhibitor of de novo sphingolipid biosynthesis was fumonisin B1. There are now 11 identified fungal inhibitors of ceramide synthase (CS) or "fumonisin-like" compounds. Most of the fumonisin-like inhibitors are structurally sphingoid-like. There are also several newly discovered fungal inhibitors of another enzyme in the de novo sphingolipid biosynthesis pathway; serine palmitoyltransferase (SPTase). One of the SPTase inhibitors is named ISP-I and in this paper we have defined all fungal SPTase inhibitors as being "ISP-I-like". While CS inhibitors are toxic to animals, plants, and fungi, the SPTase inhibitors are known to cause farm animal or plant disease, but are potent inhibitors of fungal growth. Very little is known about their toxicity in animals. There are at least 24 fungal SPTase inhibitors produced by a variety of fungi. Given that the fungal inhibitors of sphingolipid biosynthesis are chemically and biologically diverse, two bioassays have been developed to screen for fumonisin-like or ISP-I-like activity in tissues, plant products, or fungal culture materials. These bioassays are based on the changes in free sphingoid base concentration that occurs when the enzymes are inhibited. The bioassays have the advantage that they are functionally rather than chemically specific and thus will detect CS and SPTase inhibitors regardless of their chemical structure.