Synthesis of N-(4′-Pyridoxyl)Sphingosine and its Uptake and Metabolism by Isolated Cells

Abstract

N-(4′-Pyridoxyl)sphingosine was synthesized and characterized as a stable compound for specialized delivery of a bioactive lipid. It was found to be facilely taken up by hepatocytes although by a mechanism more typical for lipids than the one used by natural vitamin B₆. Some of theN-(4′-pyridoxyl)sphingosine was metabolically acted upon inside the cell to release pyridoxal 5′-phosphate and sphingosine, but formation of pyridoxal 5′-phosphate from the synthetic compound was poor compared with natural vitamin forms of B₆, which may partly be due to entrapment within cell membranes and to constraints at the level of cytosolic pyridoxal kinase which is responsible for phosphorylation of the vitamin. Unlike the parent long-chain base, the B₆ conjugate was not particularly cytotoxic. Furthermore, the compound was neither an activator nor inhibitor of the respiratory burst of human neutrophils. These findings identify N-(4′-pyridoxyl)sphingosine as an interesting tool for studies of the cellular transport, metabolism, and functions of both vitamin B₆ and sphingosine.

Key Words:

• N-(4′-pyridoxyl)sphingosine
• vitamin B₆ analog uptake
• rat liver cells.