Sphinganine 1-phosphate metabolism in cultured skin fibroblasts : evidence for the existence of a sphingosine phosphatase

• Published in: Biochemical journal Vol. 299; no. 3; pp. 597 - 601
• Main Authors: VAN VELDHOVEN, P. P, MANNAERTS, G. P
• Format: Journal Article
• Language: English
• Published: Colchester Portland Press 01.05.1994
• Subjects: Adrenoleukodystrophy - enzymology; Adrenoleukodystrophy - metabolism; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Cells, Cultured; Child; Fibroblasts - enzymology; Fundamental and applied biological sciences. Psychology; Humans; Hydrolysis; Lipids; Other biological molecules; Oxidation-Reduction; Phosphoric Monoester Hydrolases - metabolism; Phosphorylation; Saccharomyces cerevisiae Proteins; Sphingolipids; Sphingosine - analogs & derivatives; Sphingosine - metabolism; Zellweger Syndrome - enzymology; Zellweger Syndrome - metabolism; Human; Cell culture; Enzyme; Sphingolipid; Phosphoric monoester hydrolases; Hydrolases; Esterases; Skin; Metabolism; Fibroblast; Sphingosin; Uptake
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj2990597

On addition of [4,5-3H]sphinganine 1-phosphate to human fibroblast monolayers, the label was efficiently removed from the culture medium. In contrast with the reported stability of phosphorylated sphingenine in 3T3 cells [Desai, Zhang, Olivera, Mattie and Spiegel (1992). J. Biol. Chem. 267, 23122-23128] and B16 melanoma cells [Sadahira, Ruan, Hakomuri and Igarashi (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 9686-9690], sphinganine 1-phosphate appeared to be subjected to a fast and extensive metabolism in fibroblasts, the major pathways being cleavage and dephosphorylation. The first of these pathways, catalysed by sphingosine-phosphate lyase, resulted in the formation of labelled palmitaldehyde, which was recovered, mainly after oxidation, in glycerophospholipids in an ester bond. A smaller part of the palmitaldehyde was reduced and incorporated in alk(en)ylphospholipids. Dephosphorylation of spinganine 1-phosphate, a hitherto overlooked pathway catalysed by an unknown phosphatase(s), gave rise to sphinganine, which was converted by N-acylation into ceramide and then incorporated in spingomyelin and glycosphingolipids.