Ongoing studies of novel 1‐deoxy‐sphinglipids in food

Abstract

Sphingolipids have been classically defined as having sphingoid base backbones that are 1, 3‐dihydroxy, 2‐amino‐alkanes and – alkenes; however, humans and other organisms also produce sphingoid bases without the 1‐hydroxyl group (Chem Rev. 111:6387–422, 2011). These are very interesting structural variants because such compounds have been found in screens of aquatic organisms for anti‐cancer agents, and one (1‐deoxysphinganine, a.k.a. “spisulosine” and “ES‐285,” from the arctic surf clam Spisula polynyma) has shown enough promise to undergo human phase I clinical trials; and a synthetic sphingoid base analog (Enigmol) that lacks the 1‐hydroxyl‐group has anti‐tumor efficacy for colon and prostate cancer in animal models (H. Symolon et al., Mol. Cancer Ther. 10:648–57, 2011). We have developed methods for analysis of 1‐deoxy‐sphingoid bases and their N‐acyl metabolites using liquid chromatography, electrospray ionization tandem mass spectrometry and have begun to survey their occurrence in cells, tissues, and food as well as factors that influence their metabolism. These ongoing studies have found that substantial amounts (>;1 nmol/g dry weight) are present in some aquatic foods (squid and octopus), and the amounts in other meats (beef, chicken and pork) and vegetables are noteworthy. The 1‐ deoxysphingoid bases are found primarily as the N‐acyl‐derivatives rather than as the free amine, as is the case for classical sphingoid bases in most biological materials. The amounts of the 1‐deoxy‐sphingolipids are lower than “classical” sphingolipids in the foods analyzed thus far, but their relative efficacy might be comparable (or possibly greater) because 1‐deoxy‐sphingoid bases are readily absorbed because they cannot be phosphorylated and degraded in intestinal cells.Grant Funding Source: NCI (CA137812) and NIGMS (GM069338 and GM76217)