cytosolic 5'-nucleotidase cN-II is implicated in drug resistance in patients and dephosphorylates 5-fluoro-dUMP, 3'-azido-3-dTMP, 2'-chloro-2'-deoxyAMP, and related compounds, which represent the monophosphorylated forms of nucleoside prodrugs
enzyme deficient mice exhibit decreased callus size after intramembranous bone repair and reduced alkaline phosphatase activity during intramembranous bone healing. Enzyme deficiency leads to decreased osteoclast activity during the remodeling phase of intramembranous bone healing
the knockdown of enzyme expression in cultured intestinal epithelial cells results in dramatic defects in intraepithelial localization and replication as well as defective transepithelial translocation by Salmonella spp.
5'-nucleotidases are involved in the purine and pyrimidine nucleotide metabolic pathways, overview. CD73 enzymatic activity is implicated in two major extracellular metabolic pathways with distinct physiological roles, extracellular adenosine nucleotide and NAD+ metabolism
the key and rate-limiting enzyme in the ectonucleotidase pathway is ecto-5'-nucleotidase, which catalyzes the final step of dephosphorylation of AMP to adenosine
Trichomonas foetus is devoid of the ability to synthesize purine nucleotides de novo, depending instead on salvaging purines from the host environment. Ecto-5'-nucleotidase catalyzes the final step of extracellular nucleotide degradation, the hydrolysis of nucleoside 5'-monophosphates to the corresponding nucleosides and phosphate
the key and rate-limiting enzyme in the ectonucleotidase pathway is ecto-5'-nucleotidase, which catalyzes the final step of dephosphorylation of AMP to adenosine
5'-nucleotidase activities regulate the quantity of nucleotides generated from both de novo and salvage pathways, overview. 5'-Nucleotidase designates a set of enzymes, which catalyze the hydrolysis of ribonucleoside and deoxyribonucleoside monophosphates into the corresponding nucleosides plus phosphate. 5'-Nucleotidases are classified according to subcellular localization, nucleobase specificity and their ability to hydrolyze deoxynucleoside monophosphate substrates. Membrane-bound 5'-nucleotidases are ectoenzymes principally involved in salvage of extracellular nucleosides, and often display a preference toward adenosine monophosphate, thereby modulating signal transduction cascades involving purinergic receptors. Cytosolic 5'-nucleotidases are members of the haloacid dehalogenase superfamily of enzymes, which are two-domain proteins containing a modified Rossman fold as the core and a variable cap structure. Extracellular and intracellular 5'-nucleotidase activities participate in purine and pyrimidine salvage to support balanced synthesis of nucleotides, which is critical for maintaining high fidelity DNA replication. The major physiological roles for CD73 in extracellular adenosine metabolism are severalfold, overview. cNII is subject to complex allosteric regulation
5'-nucleotidase UshA is required for growth when nucleotides are provided as the sole source of phosphate, a condition that is likely relevant to bacterial growth in the wild
cytosolic 5'-nucleotidase II catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates and participates in the regulation of purine nucleotide pools within the cell
ISN1 is responsible for virtually all IMP 5'-nucleotidase activity in budding yeast cells and is required for cells to release inosine into the culture medium
the ecto-5'-nucleotidase plays a role in the control of extracellular nucleotide concentrations in the cell and is involved in the release of free adenosine into extracellular medium
the two domains can be expressed individually in Escherichia coli and fold independently. The C-terminal domain, which contains the substrate-binding pocket, is completely inactive while the N-terminal domain with the two-metal-ion-centers and the core catalytic residues exhibits significant activity, especially towards substrates with activated phosphate bonds such as ATP, ADP, 4-nitrophenyl phosphate. The two domains do not reconstitute the full-length protein from the two folded individual domains
transgenic mice expressing a dominant active mutant of downstream regulatory element antagonist modulator, daDREAM, show a drastic reduction of the amount of transcript of Ca2+-activated nucleotidase. Ca2+-activated nucleotidase down-regulation is also found in neuroblastoma SH-SY5Y cells stably overexpressing wild type DREAM or daDREAM, thus providing a simple cell model to investigate the protein maturation pathway. The down-regulation of CANT1 is associated with reduced protein secretion and increased degradation rates
upon blockade of enzyme by concanavalin A, the strength of adhesion to different extracellular matrix proteins is not altered, but at the same time the invasion ability of the cells is decreased. Knocking down the enzyme in melanoma cells does not influence cell invasion but abolishes their migration on tenascin C, indicating that an enzyme-tenascin C complex is involved in cell migration and invasion and thus in the regulation of melanoma progression
the enzyme promotes hepatocellular carcinoma growth and metastasis and upregulates the expression of epithelial growth factor receptor in hepatocellular carcinoma
the ecto-5'-nucleotidase plays a role in the control of extracellular nucleotide concentrations in the cell and is involved in the release of free adenosine into extracellular medium
CD73 is highly induced by ischemia and hypoxia, and increased expression in cardiac ischemia is mediated by a positive feedback loop involving adenosine
unilateral cortical stab injury causes a rapid and irreversible loss of the enzyme from neurons, accounting for a decrease in the overall enzyme expression, accompanied with a gradual increase in e-5NT-positive astrocytes, accounting for upregulation of the enzyme levels in the injured area. CSI induces dynamic changes in the expression pattern of e-5NT that modify the ATP/adenosine ratio and the extent of P1 and P2 receptors activation and, therefore, outcome of the pathological processes after cortical stab injury
unilateral cortical stab injury causes a rapid and irreversible loss of the enzyme from neurons, accounting for a decrease in the overall enzyme expression, accompanied with a gradual increase in e-5NT-positive astrocytes, accounting for upregulation of the enzyme levels in the injured area. CSI induces dynamic changes in the expression pattern of e-5NT that modify the ATP/adenosine ratio and the extent of P1 and P2 receptors activation and, therefore, outcome of the pathological processes after cortical stab injury