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. 1984 Aug;26(2):211–213. doi: 10.1128/aac.26.2.211

Comparative inhibition of bacterial and microsomal 3-ketodihydrosphingosine synthetases by L-cycloserine and other inhibitors.

K S Sundaram, M Lev
PMCID: PMC284122  PMID: 6486763

Abstract

Eleven compounds were examined for their capacity to inhibit the first enzyme of the sphingolipid pathway, 3-ketodihydrosphingosine synthetase. Of these, L-cycloserine was the most potent, affecting both bacterial and brain microsomal enzymes to a significant degree at 0.04 mM. D- and L-cycloserine irreversibly inactivated the enzyme, indicating a suicide substrate mode of action. L-Cycloserine was a more potent inhibitor of the growth of Bacteroides levii than was D-cycloserine, indicating that inhibition of sphingolipid synthesis could be a factor in the growth inhibition.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Braun P. E., Morell P., Radin N. S. Synthesis of C18- and C20-dihydrosphingosines, ketodihydrosphingosines, and ceramides by microsomal preparations from mouse brain. J Biol Chem. 1970 Jan 25;245(2):335–341. [PubMed] [Google Scholar]
  2. Cattabeni F., Maggi A., DeAngelis L., Bruno F., Racagni G. A simple approach to study the effect of haloperidol on GABA functional activity in the nigro-striatal system. J Neurochem. 1977 Jun;28(6):1407–1408. doi: 10.1111/j.1471-4159.1977.tb12343.x. [DOI] [PubMed] [Google Scholar]
  3. Di Mari S. J., Brady R. N., Snell E. E. Biosynthesis of sphingolipid bases. IV. The biosynthetic origin of sphingosine in Hansenula ciferri. Arch Biochem Biophys. 1971 Apr;143(2):553–565. doi: 10.1016/0003-9861(71)90240-2. [DOI] [PubMed] [Google Scholar]
  4. Kollonitsch J., Perkins L. M., Patchett A. A., Doldouras G. A., Marburg S., Duggan D. E., Maycock A. L., Aster S. D. Selective inhibitors of biosynthesis of aminergic neurotransmitters. Nature. 1978 Aug 31;274(5674):906–908. doi: 10.1038/274906a0. [DOI] [PubMed] [Google Scholar]
  5. Lev M., Milford A. F. Energy-dependent incorporation of sphingolipid precursors and fatty acids in Bacteriodes melaninogenicus. J Bacteriol. 1977 Apr;130(1):445–454. doi: 10.1128/jb.130.1.445-454.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lev M., Milford A. F. The 3-ketodihydrosphingosine synthetase of Bacteroides melaninogenicus: induction by vitamin K. Arch Biochem Biophys. 1973 Aug;157(2):500–508. doi: 10.1016/0003-9861(73)90668-1. [DOI] [PubMed] [Google Scholar]
  7. Lev M., Milford A. F. The 3-ketodihydrosphingosine synthetase of Bacteroides melaninogenicus: partial purification and properties. Arch Biochem Biophys. 1981 Dec;212(2):424–431. doi: 10.1016/0003-9861(81)90384-2. [DOI] [PubMed] [Google Scholar]
  8. Morell P., Radin N. S. Specificity in ceramide biosynthesis from long chain bases and various fatty acyl coenzyme A's by brain microsomes. J Biol Chem. 1970 Jan 25;245(2):342–350. [PubMed] [Google Scholar]
  9. Rizza V., Tucker A. N., White D. C. Lipids of Bacteroides melaninogenicus. J Bacteriol. 1970 Jan;101(1):84–91. doi: 10.1128/jb.101.1.84-91.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. SCOTTO P., MONACO P., SCARDI V., BONAVITA V. NEUROCHEMICAL STUDIES WITH L-CYCLOSERINE, A CENTRAL DEPRESSANT AGENT. J Neurochem. 1963 Dec;10:831–839. doi: 10.1111/j.1471-4159.1963.tb11908.x. [DOI] [PubMed] [Google Scholar]
  11. Sundaram K. S., Lev M. Inhibition of sphingolipid synthesis by cycloserine in vitro and in vivo. J Neurochem. 1984 Feb;42(2):577–581. doi: 10.1111/j.1471-4159.1984.tb02716.x. [DOI] [PubMed] [Google Scholar]
  12. Sundaram K. S., Lev M. L-cycloserine inhibition of sphingolipid synthesis in the anaerobic bacterium Bacteroides levii. Biochem Biophys Res Commun. 1984 Mar 15;119(2):814–819. doi: 10.1016/s0006-291x(84)80323-x. [DOI] [PubMed] [Google Scholar]
  13. TOURTELLOTTE M. E., JENSEN R. G., GANDER G. W., MOROWITZ H. J. LIPID COMPOSITION AND SYNTHESIS IN THE PLEUROPNEUMONIA-LIKE ORGANISM MYCOPLASMA GALLISEPTICUM. J Bacteriol. 1963 Sep;86:370–379. doi: 10.1128/jb.86.3.370-379.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wells G. B., Lester R. L. The isolation and characterization of a mutant strain of Saccharomyces cerevisiae that requires a long chain base for growth and for synthesis of phosphosphingolipids. J Biol Chem. 1983 Sep 10;258(17):10200–10203. [PubMed] [Google Scholar]

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