Mannosamine can replace glucosamine in glycosylphosphatidylinositols of Plasmodium falciparum in vitro

N Azzouz, C S de Macedo, M A J Ferguson, Terry K Smith, R T Schwarz

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Mannosamine (2-deoxy-2-amino-D-mannose) is unable to block GP1 biosynthesis in neither parasite development nor GPI biosynthesis were blocked by mannosamine treatment in P. falciparum cultures. Further, it was shown by metabolic labeling with [H-3]mannosamine and subsequent monosaccharide analysis by high pH anion exchange chromatography that mannosamine is converted at a high rate into glucosamine. Both mannosamine and glucosamine are incorporated into P.falciparum glycolipids, but the characterization of mannosamine-labeled glycolipids synthesized in vivo proved difficult. Therefore. it cell-free system was developed to investigate the incorporation of [H-3]mannosamine into glycolipids in P falciparum. It was observed that mannosamine is incorporated in vitro into P falciparum glycolipids, which possess a phosphate group. Chemical (nitrous acid deamination, mild acid hydrolysis and alkaline hydrolysis) and enzymatic (PI-PLC) treatments of [H-3]mannosamine-labeled glycolipids synthesized in vitro showed the presence or GPIs. Further analyses by Bio-Gel P4 size-exclusion chromatography and HPAEC demonstrated the presence of a mannosamine-containing GPI-like structures, where mannosamine is incorporated instead of glucosamine, i.e. Man(3)-ManN-PI, This utilization of rnannosamine is novel and not been described for any other cellular or parasitic system. (c) 2005 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)12-24
Number of pages13
JournalMolecular and Biochemical Parasitology
Volume142
Issue number1
DOIs
Publication statusPublished - Jul 2005

Keywords

  • Plasmodium falciparum
  • GPI
  • mannosamine
  • GLYCOSYL-PHOSPHATIDYLINOSITOL ANCHOR
  • LIPID-LINKED OLIGOSACCHARIDES
  • ASEXUAL ERYTHROCYTIC STAGES
  • TRYPANOSOMA-BRUCEI
  • BIOSYNTHETIC-PATHWAY
  • INTRAERYTHROCYTIC STAGE
  • SUBSTRATE-SPECIFICITY
  • PROTEIN GLYCOSYLATION
  • AFRICAN TRYPANOSOMES
  • INOSITOL ACYLATION

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