Skip to main content
ARS Home » Research » Publications at this Location » Publication #143471
Title: INSTABILITY OF N-ACETYLATED FUMONISIN B1 (FA1) AND THE IMPACT ON INHIBITION OF CERAMIDE SYNTHASE IN RAT LIVER SLICES

Author
item Norred, William
item Riley, Ronald
item Meredith, Filmore
item Poling, Stephen
item Plattner, Ronald

Submitted to: Mycopathologia
Publication Type: Abstract Only
Publication Acceptance Date: 1/15/2002
Publication Date: 6/1/2002
Citation: NORRED, W.P., RILEY, R.T., MEREDITH, F.I., POLING, S.M., PLATTNER, R.D. 2002. INSTABILITY OF N-ACETYLATED FUMONISIN B1 (FA1) AND THE IMPACT ON INHIBITION OF CERAMIDE SYNTHASE IN RAT LIVER SLICES. MYCOPATHOLOGIA. v.155. Abstract p.35.

Interpretive Summary: Abstract

Technical Abstract: Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides. It inhibits ceramide synthase, which is a proposed underlying mechanism responsible for the myriad of toxic endpoints observed. We previously reported that N-acetylation of FB1 prevents ceramide synthase inhibition, but cautioned that impure preparations of FA1 can contain a contaminant with the ability to inhibit ceramide synthase. We now report that FA1 spontaneously rearranges to O-acetylated analogs. These rearrangement products are putative inhibitors of ceramide synthase. Rat liver slices exposed to impure FA1 containing O-acetylated FB1 had sphinganine/sphingosine (Sa/So) ratios of 1.15-1.64. Control slices had Sa/So ratios of 0.07-0.24. Clean-up to remove the O-acetylated FB1 yielded purified FA1, which produced Sa/So ratios in liver slices of 0.08-0.18. After storage for ca. 1 year as either a dry powder in a desiccator, or as a dried film at 4° C, the purified FA1 again contained O-acetylated FB1, and was capable of ceramide synthase inhibition. FA1 was most stable in neutral solution, but in acidic solution the equilibrium shifted towards the O-acetylated forms. FA1 in solid form also rearranged, but more slowly than in acid solution. Since FA1 is considerably less cytotoxic than FB1, these results provide additional support for the conclusion that a primary amino group is necessary for both ceramide synthase inhibition and toxicity.