title: Inhibition of UDP-N-acetylglucosamine pyrophosphorylase by uridine.
abstract: UDP-N-acetylglucosamine pyrophosphorylases (UTP: 2-acetamido-2-deoxy-alpha-D-glucose-1-phosphate uridylyltransferase, EC 2.7.7.23) from baker's yeast and Neurospora crassa IFO 6178 were inhibited by uridine which is the nucleoside moiety of UDP-GlcNAc. The inhibition was shown in both directions of pyrophosphorolysis and of synthesis of UDP-GlcNAc. Kinetic analysis revealed that uridine demonstrated a noncompetitive type of inhibition with UDP-GlcNAc and competitive inhibition with PPi. The Ki values for the baker's yeast enzyme were 1.8 mM for UDP-GlcNAc and 0.16 mM for PPi, and the values for the Neurospora enzyme were 1.1 mM for UDP-GlcNAc and 0.15 mM for PPi, respectively. Uridine did not bind irreversibly to the enzyme, as the activity was restored with dialysis. No other nucleosides caused inhibition of the enzyme activity except uridine. Some uridine derivatives, such as 5-hydroxyuridine, 5,6-dihydrouridine and pseudouridine, also inhibited the enzyme activity. But doexyuridine showed only slight inhibition, and 5'-UMP and orotidine caused no inhibition of the enzyme activity.
mesh_terms: D007700:Kinetics; D009492:Neurospora crassa / Q000201:enzymology; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011560:Pseudouridine / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D014529:Uridine / Q000031:analogs & derivatives / Q000494:pharmacology*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D011560:Pseudouridine; D014537:Uridine Diphosphate N-Acetylglucosamine; C010922:5,6-dihydrouridine; C010194:5-hydroxyuridine; D009713:Nucleotidyltransferases; C023226:UDPacetylglucosamine pyrophosphorylase; D014529:Uridine