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. 1994 May 1;299(Pt 3):597–601. doi: 10.1042/bj2990597

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

P P Van Veldhoven 1, G P Mannaerts 1
PMCID: PMC1138063  PMID: 8192648

Abstract

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.

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Selected References

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  1. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  2. Billah M. M., Anthes J. C. The regulation and cellular functions of phosphatidylcholine hydrolysis. Biochem J. 1990 Jul 15;269(2):281–291. doi: 10.1042/bj2690281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buehrer B. M., Bell R. M. Sphingosine kinase: properties and cellular functions. Adv Lipid Res. 1993;26:59–67. [PubMed] [Google Scholar]
  4. Clarke N. G., Dawson R. M. Alkaline O leads to N-transacylation. A new method for the quantitative deacylation of phospholipids. Biochem J. 1981 Apr 1;195(1):301–306. doi: 10.1042/bj1950301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Desai N. N., Zhang H., Olivera A., Mattie M. E., Spiegel S. Sphingosine-1-phosphate, a metabolite of sphingosine, increases phosphatidic acid levels by phospholipase D activation. J Biol Chem. 1992 Nov 15;267(32):23122–23128. [PubMed] [Google Scholar]
  6. Exton J. H. Signaling through phosphatidylcholine breakdown. J Biol Chem. 1990 Jan 5;265(1):1–4. [PubMed] [Google Scholar]
  7. Imamura S., Horiuti Y. Purification of Streptomyces chromofuscus phospholipase D by hydrophobic affinity chromatography on palmitoyl cellulose. J Biochem. 1979 Jan;85(1):79–95. doi: 10.1093/oxfordjournals.jbchem.a132334. [DOI] [PubMed] [Google Scholar]
  8. Merrill A. H., Jr, Wang E. Biosynthesis of long-chain (sphingoid) bases from serine by LM cells. Evidence for introduction of the 4-trans-double bond after de novo biosynthesis of N-acylsphinganine(s). J Biol Chem. 1986 Mar 15;261(8):3764–3769. [PubMed] [Google Scholar]
  9. Rother J., van Echten G., Schwarzmann G., Sandhoff K. Biosynthesis of sphingolipids: dihydroceramide and not sphinganine is desaturated by cultured cells. Biochem Biophys Res Commun. 1992 Nov 30;189(1):14–20. doi: 10.1016/0006-291x(92)91518-u. [DOI] [PubMed] [Google Scholar]
  10. Sadahira Y., Ruan F., Hakomori S., Igarashi Y. Sphingosine 1-phosphate, a specific endogenous signaling molecule controlling cell motility and tumor cell invasiveness. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9686–9690. doi: 10.1073/pnas.89.20.9686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Stoffel W., LeKim D., Heyn G. Metabolism of sphingosine bases. XIV. Sphinganine (dihydrosphingosine), an effective donor of the alk-1-enyl chain of plasmalogens. Hoppe Seylers Z Physiol Chem. 1970 Jul;351(7):875–883. doi: 10.1515/bchm2.1970.351.2.875. [DOI] [PubMed] [Google Scholar]
  12. Stoffel W., LeKim D. Studies on the biosynthesis of plasmalogens. Precursors in the biosynthesis of plasmalogens: on the stereospecificity of the biochemical dehydrogenation of the 1-O-alkyl glyceryl to the 1-O-alk-1'-enyl glyceryl ether bond. Hoppe Seylers Z Physiol Chem. 1971 Mar;352(3):501–511. doi: 10.1515/bchm2.1971.352.1.501. [DOI] [PubMed] [Google Scholar]
  13. Van Veldhoven P. P., Bell R. M. Effect of harvesting methods, growth conditions and growth phase on diacylglycerol levels in cultured human adherent cells. Biochim Biophys Acta. 1988 Mar 25;959(2):185–196. doi: 10.1016/0005-2760(88)90030-6. [DOI] [PubMed] [Google Scholar]
  14. Van Veldhoven P. P., Bishop W. R., Bell R. M. Enzymatic quantification of sphingosine in the picomole range in cultured cells. Anal Biochem. 1989 Nov 15;183(1):177–189. doi: 10.1016/0003-2697(89)90186-3. [DOI] [PubMed] [Google Scholar]
  15. Van Veldhoven P. P., Huang S., Eyssen H. J., Mannaerts G. P. The deficient degradation of synthetic 2- and 3-methyl-branched fatty acids in fibroblasts from patients with peroxisomal disorders. J Inherit Metab Dis. 1993;16(2):381–391. doi: 10.1007/BF00710285. [DOI] [PubMed] [Google Scholar]
  16. Van Veldhoven P. P., Mannaerts G. P. Subcellular localization and membrane topology of sphingosine-1-phosphate lyase in rat liver. J Biol Chem. 1991 Jul 5;266(19):12502–12507. [PubMed] [Google Scholar]
  17. Van Veldhoven P. P., Matthews T. J., Bolognesi D. P., Bell R. M. Changes in bioactive lipids, alkylacylglycerol and ceramide, occur in HIV-infected cells. Biochem Biophys Res Commun. 1992 Aug 31;187(1):209–216. doi: 10.1016/s0006-291x(05)81480-9. [DOI] [PubMed] [Google Scholar]
  18. Zhang H., Buckley N. E., Gibson K., Spiegel S. Sphingosine stimulates cellular proliferation via a protein kinase C-independent pathway. J Biol Chem. 1990 Jan 5;265(1):76–81. [PubMed] [Google Scholar]
  19. Zhang H., Desai N. N., Olivera A., Seki T., Brooker G., Spiegel S. Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J Cell Biol. 1991 Jul;114(1):155–167. doi: 10.1083/jcb.114.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. van Veldhoven P. P., Mannaerts G. P. Sphingosine-phosphate lyase. Adv Lipid Res. 1993;26:69–98. [PubMed] [Google Scholar]

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