LIQUID-CHROMATOGRAPHIC DETERMINATION OF SPHINGANINE AND SPHINGOSINE -USE OF THE FREE SPHINGANINE-TO-SPHINGOSINE RATIO AS A BIOMARKER FOR CONSUMPTION OF FUMONISINS

Because the chemical structure of fumonisin BI (FB1) has several struc tural features in common with the sphingoid bases, sphingosine and dih ydrosphingosine (sphinganine), we tested the hypothesis that the fumon isins might alter the normal cellular activity or the metabolism of en dogenous free sphingoid bases. FB1 was found to be a potent inhibitor of de novo sphingolipid biosynthesis in vitro, its primary target bein g sphinganine N-acyltransferase. This inhibition resulted in a decreas e in the biosynthesis of sphingosine and an accumulation of free sphin ganine, an intermediate in the de novo biosynthetic pathway for comple x sphingolipids. These findings led to the hypothesis that consumption of feed containing fumonisins should cause an increase in the ratio o f free sphinganine to free sphingosine in tissues and serum. Data cons istent with this hypothesis have been obtained from horses and pigs th at consumed feed containing fumonisin-contaminated corn screenings and from rats fed feed supplemented with fumonisin-containing fungal cult ure materials or pure FB1. Thus, the ratio of free sphinganine to free sphingosine shows promise as a tissue, urine, or serum marker for ani mals consuming feed containing fumonisins. The present paper provides a detailed description of the extraction of free sphingoid bases and t he liquid chromatographic method we used for determining the relative amounts of free sphingosine and free sphinganine in serum, urine, and various tissues of animals. Study results are summarized, and the rati o of free sphinganine to free sphingosine is discussed as a presumptiv e test for identifying animals consuming fumonisin-contaminated feed.