Allosteric regulation of the partitioning of glucose-1-phosphate between glycogen and trehalose biosynthesis in Mycobacterium tuberculosis.

Mycobacterium tuberculosis is a pathogenic prokaryote adapted to survive in hostile environments. In this organism and other Gram-positive actinobacteria, the metabolic pathways of glycogen and trehalose are interconnected.
In this work we show the production, purification and characterization of recombinant enzymes involved in the partitioning of glucose-1-phosphate between glycogen and trehalose in M. tuberculosis H37Rv, namely: ADP-glucose pyrophosphorylase, glycogen synthase, UDP-glucose pyrophosphorylase and trehalose-6-phosphate synthase. The substrate specificity, kinetic parameters and allosteric regulation of each enzyme were determined. ADP-glucose pyrophosphorylase was highly specific for ADP-glucose while trehalose-6-phosphate synthase used not only ADP-glucose but also UDP-glucose, albeit to a lesser extent. ADP-glucose pyrophosphorylase was allosterically activated primarily by phosphoenolpyruvate and glucose-6-phosphate, while the activity of trehalose-6-phosphate synthase was increased up to 2-fold by fructose-6-phosphate. None of the other two enzymes tested exhibited allosteric regulation.
Results give information about how the glucose-1-phosphate/ADP-glucose node is controlled after kinetic and regulatory properties of key enzymes for mycobacteria metabolism.
This work increases our understanding of oligo and polysaccharides metabolism in M. tuberculosis and reinforces the importance of the interconnection between glycogen and trehalose biosynthesis in this human pathogen.
AuthorsMatías D Asención Diez, Ana M Demonte, Karl Syson, Diego G Arias, Andrii Gorelik, Sergio A Guerrero, Stephen Bornemann, Alberto A Iglesias
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1850 Issue 1 Pg. 13-21 (Jan 2015) ISSN: 0006-3002 [Print] Netherlands
PMID25277548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014. Published by Elsevier B.V.
Chemical References
  • Bacterial Proteins
  • Glucosephosphates
  • Recombinant Proteins
  • Glucose-6-Phosphate
  • Glycogen
  • Trehalose
  • glucose-1-phosphate
  • Glucosyltransferases
  • Glycogen Synthase
  • trehalose-6-phosphate synthase
  • Glucose-1-Phosphate Adenylyltransferase
  • UTP-Glucose-1-Phosphate Uridylyltransferase
  • Allosteric Regulation
  • Bacterial Proteins (genetics, metabolism)
  • Glucose-1-Phosphate Adenylyltransferase (genetics, metabolism)
  • Glucose-6-Phosphate (metabolism)
  • Glucosephosphates (metabolism)
  • Glucosyltransferases (genetics, metabolism)
  • Glycogen (biosynthesis)
  • Glycogen Synthase (genetics, metabolism)
  • Kinetics
  • Metabolic Networks and Pathways
  • Models, Biological
  • Mycobacterium tuberculosis (enzymology, metabolism)
  • Recombinant Proteins (metabolism)
  • Substrate Specificity
  • Trehalose (biosynthesis)
  • UTP-Glucose-1-Phosphate Uridylyltransferase (genetics, metabolism)

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