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UDP-N-acetylglucosamine pyrophosphorylase, a key enzyme in encysting Giardia, is allosterically regulated.

Abstract
Giardia synthesizes UDP-GalNAc during cyst wall formation (encystment) via a pathway of inducible enzymes similar to that used to synthesize chitin or peptidoglycan and that includes the UTP-requiring UDP-N-acetylglucosamine pyrophosphorylase. Although it has never been reported as a regulatory enzyme in any system studied to date, kinetic data including Hill plots demonstrate clearly that UDP-N-acetylglucosamine pyrophosphorylase activity, purified from encysting Giardia, is allosterically activated anabolically by physiological levels of glucosamine 6-phosphate (3 microm). Capillary electrophoresis demonstrates that within 24 h after trophozoites are induced to encyst, the level of glucosamine 6-phosphate increases 3-fold over that of non-encysting cells and that by 48 h into encystment the level of glucosamine 6-phosphate has decreased to non-encysting levels or below. UDP-N-acetylglucosamine pyrophosphorylase protein is present constitutively in encysting as well as non-encysting cells. UDP-N-acetylglucosamine pyrophosphorylase immunoaffinity purified from encysting and non-encysting cells exhibited the same molecular weight, amino acid composition, and circular dichroism spectra. Moreover, regardless of whether the enzyme came from encysting or non-encysting cells, the change in its circular dichroism spectra and up to a 6-fold increase in its specific activity anabolically were due to its activation with glucosamine 6-phosphate. Thus, the data support the idea that UDP-N-acetylglucosamine pyrophosphorylase is a major regulatory point in amino sugar synthesis in encysting Giardia and that its allosteric anabolic activation may shift the equilibrium of this pathway toward UDP-GalNAc synthesis.
AuthorsD A Bulik, P van Ophem, J M Manning, Z Shen, D S Newburg, E L Jarroll
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 275 Issue 19 Pg. 14722-8 (May 12 2000) ISSN: 0021-9258 [Print] United States
PMID10799561 (Publication Type: Journal Article)
Chemical References
  • Amino Acids
  • Nucleotidyltransferases
  • UDPacetylglucosamine pyrophosphorylase
Topics
  • Allosteric Regulation
  • Amino Acids (analysis)
  • Animals
  • Blotting, Western
  • Chromatography, Affinity
  • Circular Dichroism
  • Enzyme Activation
  • Giardia lamblia (enzymology)
  • Kinetics
  • Nucleotidyltransferases (chemistry, isolation & purification, metabolism)
  • Substrate Specificity

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