Phosphatidylarsenocholine, one of the major arsenolipids in marine organisms: Synthesis and metabolism in mice

Marine organisms contain arsenic at high levels, both in water-soluble and lipid-soluble forms. In contrast to the accumulated knowledge on water-soluble arsenic compounds, toxicological properties of lipid-soluble arsenic compounds (arsenolipids) have been little understood. Therefore, this study was aimed to clarify the metabolism of phosphatidylarsenocholine, one of the major arsenolipids so far identified in marine organisms. Phosphatidylarsenocholine (dipalmitoyl) was synthesized from phosphatidylcholine (dipalmitoyl) and arsenocholine by the transphosphatidylation reaction with phospholipase D and its synthesis was confirmed by LC/ESI-MS analysis. When phosphatidylarsenocholine was orally administered to mice at 45 μg As/mouse, arsenic was excreted mainly in urine almost in parallel with the time elapsed. The excretion rate was considerably slow compared to the case of water-soluble arsenic compounds but more than 90% of the administered arsenic was excreted within 144 h after administration. Analysis by LC/ESI-MS revealed that the major urinary metabolite was arsenobetaine, although small amounts of arsenocholine were detected in urine up to 72 h. These results allowed us to conclude that phosphatidylarsenocholine is mostly absorbed from the gastrointestinal tract in mice, metabolized to arsenobetaine and slowly excreted mainly in urine.