TY - JOUR
T1 - The effects of phenylmethylsulfonyl fluoride on inositol-acylation and fatty acid remodeling in African trypanosomes
AU - Güther, Maria Lucia S.
AU - Masterson, Wayne J.
AU - Ferguson, Michael A. J.
N1 - Medline is the source for the MeSH terms of this document.
PY - 1994/7/15
Y1 - 1994/7/15
N2 - Phenylmethylsulfonyl fluoride (PMSF) has been shown to inhibit the addition of ethanolamine phosphate to glycosylphosphatidylinositol (GPI) intermediates in Trypanosoma brucei (Masterson W. J., and Ferguson, M. A. J. (1991) EMBO J. 10, 2041-2045). Here we show that the Man-GlcN-PI intermediate that accumulates in the presence of PMSF can undergo fatty acid remodeling, suggesting that the fatty acid remodeling enzymes are not specific for ethanolamine phosphate-containing GPI intermediates. We also show that PMSF inhibits the acylation of the inositol residue of GPI intermediates in bloodstream form T. brucei. Pulse-chase experiments demonstrate that glycolipid C (ethanolamine-PO-Man-GlcN-(acyl)PI) is not an obligatory precursor of glycolipid A (ethanolamine-PO-Man-GlcN-PI) and that glycolipid C can be converted to glycolipid A. These data suggest a model where glycolipid C is the terminal product of the GPI biosynthetic pathway, in dynamic equilibrium with glycolipid A. The inhibition of ethanolamine phosphate addition and inositol acylation by PMSF was also observed for procyclic forms of T. brucei but not for mammalian HeLa cells. These results suggest differences between the relevant parasite and mammalian enzymes.
AB - Phenylmethylsulfonyl fluoride (PMSF) has been shown to inhibit the addition of ethanolamine phosphate to glycosylphosphatidylinositol (GPI) intermediates in Trypanosoma brucei (Masterson W. J., and Ferguson, M. A. J. (1991) EMBO J. 10, 2041-2045). Here we show that the Man-GlcN-PI intermediate that accumulates in the presence of PMSF can undergo fatty acid remodeling, suggesting that the fatty acid remodeling enzymes are not specific for ethanolamine phosphate-containing GPI intermediates. We also show that PMSF inhibits the acylation of the inositol residue of GPI intermediates in bloodstream form T. brucei. Pulse-chase experiments demonstrate that glycolipid C (ethanolamine-PO-Man-GlcN-(acyl)PI) is not an obligatory precursor of glycolipid A (ethanolamine-PO-Man-GlcN-PI) and that glycolipid C can be converted to glycolipid A. These data suggest a model where glycolipid C is the terminal product of the GPI biosynthetic pathway, in dynamic equilibrium with glycolipid A. The inhibition of ethanolamine phosphate addition and inositol acylation by PMSF was also observed for procyclic forms of T. brucei but not for mammalian HeLa cells. These results suggest differences between the relevant parasite and mammalian enzymes.
UR - http://www.scopus.com/inward/record.url?scp=0028358821&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:0028358821
SN - 0021-9258
VL - 269
SP - 18694
EP - 18701
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 28
ER -