Disease relevance of Upp1

• Uridine phosphorylase from Novikoff rat hepatoma cells: purification, kinetic properties, and its role in uracil anabolism [1].
• Co-infusion of uridine with benzylacyclouridine, an inhibitor of uridine phosphorylase, partially prevented uridine-mediated hypothermia in mice [2].
• It is suggested that the activation of uridine phosphorylase activity during the early life of the rat may be a critical element of the onset of hypertrophy [3].

High impact information on Upp1

• The breakdown of 5-fluoro-2'-deoxyuridine (FdUrd) to 5-fluorouracil (FUra) is catalyzed by the pyrimidine nucleoside phosphorylases, uridine phosphorylase and thymidine phosphorylase [4].
• When adenosine 5'-triphosphate was included in the reaction mixture for uridine phosphorylase, FUra was rapidly channeled into FUra nucleotides via its nucleoside [5].
• Isoelectric focusing and studies with 1-(2'-deoxy-beta-D-glucopyranosyl)thymine (GPT), a specific inhibitor of uridine phosphorylase activity, were used to determine the substrate specificities of mammalian pyrimidine nucleoside phosphorylases and their cleavage of 5-fluoro-2'-deoxyuridine (FdUrd) [6].
• Inhibition of uridine phosphorylase. Synthesis and structure-activity relationships of aryl-substituted 1-((2-hydroxyethoxy)methyl)-5-(3-phenoxybenzyl)uracil [7].
• Uridine phosphorylase activity was detected in sonic extracts of six different mammalian cell lines and, in conjunction with uridine kinase, provides a route for the conversion of uracil to UMP via uridine [1].

Chemical compound and disease context of Upp1

• Uridine phosphorylase was purified 5,330-fold from Novikoff rat hepatoma cells by ammonium sulfate precipitation, DEAE-Sephadex chromatography, hydroxyapatite chromatography, and Sephadex G-200 fractionation [1].

Biological context of Upp1

• The same order of Ki values obtained for the investigated inhibitors vs uridine phosphorylase, irrespective whether the enzyme was isolated from rat intestinal mucosa (Drabikowska et al., 1987, Biochem. Pharmacol. 36, 4125-4128) or H. diminuta may point to a great similarity between binding sites on the parasite and the host enzyme [8].
• Uridine phosphorylase from Hymenolepis diminuta (Cestoda): kinetics and inhibition by pyrimidine nucleoside analogs [8].
• When PC12 cell extracts were incubated with ribose 1-phosphate, ATP and uracil they can readily catalyze the synthesis of uracil nucleotides, through a salvage pathway in which the ribose moiety of ribose 1-phosphate is transferred to uracil via uridine phosphorylase (acting anabolically), with subsequent uridine phosphorylation [9].

Anatomical context of Upp1

• It was concluded that intestinal epithelial cells are capable of degrading FdUrd to FUra and that the cells possess both uridine phosphorylase and thymidine phosphorylase activity [10].
• 2,2'-Anhydro-3'-deoxy-5-ethyluridine has a Ki value of 3.4 microM for uridine phosphorylase from rat intestinal mucosa [11].
• The same holds true for the activity of uridine phosphorylase (EC 2.4.2.3),5'-nucleotidase (EC 3.1.3.5) ATPase (EC 3.6.1.3) and of liver cytosol [12].
• Uridine phosphorylase activity of isolated plasma membranes of rat liver [13].

Associations of Upp1 with chemical compounds

• 6-Benzyl-2-thiouracil, a thymidine phosphorylase-selective inhibitor, and 1-(2'-deoxy-beta-D-glucopyranosyl)thymine, a uridine phosphorylase-selective inhibitor, each decreased the rate of FdUrd disappearance (apparent Ki, 1.4-1.6 and 3.8 mM, respectively) but had no direct effect on FUra disappearance [4].
• 2,6-Dihydroxypyridine, a uridine phosphorylase-selective inhibitor, decreased the rate of FdUrd disappearance (apparent Ki, 12.4-16.2 microM) and directly inhibited FUra elimination (apparent Ki, 4.3-5.3 microM) [4].
• These observations are consistent with the kinetic characteristics of the enzyme and provide evidence that the intracellular level of ribose-1-phosphate plays a rate-limiting role in the uptake of uracil mediated by uridine phosphorylase [1].
• Effect of 5-benzylacyclouridine, a potent inhibitor of uridine phosphorylase, on the metabolism of circulating uridine by the isolated rat liver [14].
• The apparent Ki values were as follows (in mM): 5-nitrouracil (an inhibitor of both uridine phosphorylase and thymidine phosphorylase), 0.12; 4-thiothymine (a uridine phosphorylase-selective inhibitor), 1.52; and 6-benzyl-2-thiouracil (a thymidine phosphorylase-selective inhibitor), 0.73 [10].

Analytical, diagnostic and therapeutic context of Upp1

• The enrichment factor for uridine phosphorylase in the fractions prepared by differential centrifugation was about 2.8 and by the gradient method, as much as 11.0; the respective enrichment factors for 5'-nucleotidase were 1.8 and 9 [13].

References