Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the effect of 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid (TEI-6720), an inhibitor of xanthine oxidase, on purine metabolism in the lung cancer cell line A549, the activities of adenosine deaminase, purine nucleoside phosphorylase, adenine phosphoribosyltransferase, hypoxanthine guanine phosphoribosyltransferase, xanthine oxidase, and guanase together with pyrimidine nucleoside phosphorylase were measured with or without the addition of TEI-6720, and the extracellular concentrations of hypoxanthine, xanthine, inosine, uracil, and uridine were measured after the addition of inosine or uridine to the incubation medium with or without TEI-6720. Moreover, the Na-independent nucleoside transport was determined in A549 cells with or without TEI-6720. TEI-6720 inhibited the activity of xanthine oxidase in A549 cells, but did not affect other enzymes. During incubation, TEI-6720 not only prevented a decrease in the inosine concentration in inosine-containing medium, but also a decrease in the uridine concentration in uridine-containing medium. Furthermore, the Na-independent transport of uridine was inhibited by TEI-6720 with a K(i) value of 4.1 micromol/l. These results indicate that TEI-6720 is an inhibitor of the Na-independent nucleoside transport of uridine and inosine, as well as xanthine oxidase.
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PMID:Effect of TEI-6720, a xanthine oxidase inhibitor, on the nucleoside transport in the lung cancer cell line A549. 1062 41

Adenosine- and uridine-cytidine kinases, purine-nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyl transferase, and several related enzymes, are components of the salvage pathways which reduce the loss of intracellular purine and pyrimidine rings. Although this could explain the role of these enzymes, it poses a problem of the role of the cytosolic 5'-nucleotidase. Why are nucleosides produced from nucleoside-monophosphates, only to be converted back to the same compounds? To date, it is well established that a cross talk exists between the extracellular and intracellular nucleoside metabolism. In districts, such as brain, which are dependent on salvage nucleotide synthesis, nucleosides are produced through the action of the ecto-5'-nucleotidase, the last component of a series of plasma-membrane bound enzyme proteins, catalyzing the successive dephosphorylation of released nucleoside-triphosphates. Both nucleosidetriphosphates (mainly ATP and UTP) and nucleosides (mainly adenosine), act as extracellular signals. Once transported into cell cytosol, all nucleosides are salvaged back to nucleoside-triphosphates, with the exception of inosine, whose salvage is limited to IMP. Intracellular balance of nucleosides is maintained by the action of several enzymes, such as adenosine deaminase, uridine phosphorylase and cytidine deaminase, and by at least three 5'-nucleotidases, the ADP activated AMP preferring cN-IA, the ATP-ADP activated IMP-GMP preferring cN-II, and the UMP-CMP preferring cN-III. Here we are reviewing the mechanisms whereby cytosolic 5'-nucleotidases control changes in nucleoside and nucleotide concentration, with the aim to provide a common basis for the study of the relationship between biochemistry and other related disciplines, such as physiology and pharmacology.
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PMID:The functional logic of cytosolic 5'-nucleotidases. 2399 16

5-Methyluridine (5MU) was synthesized efficiently from adenosine, thymine, and phosphate by a combination of adenosine deaminase (ADA), purine nucleoside phosphorylase (PUNP), pyrimidine nucleoside phosphorylase (PYNP), and xanthine oxidase (XOD). Adenosine was converted into inosine first by ADA. 5MU and hypoxanthine were synthesized from inosine and thymine by PUNP and PYNP. The hypoxanthine formed was converted into urate via xanthine by XOD. After inosine was completely consumed, an equilibrium state, in which 5MU, thymine, ribose-1-phosphate, and phosphate were involved, was achieved. At the equilibrium state, the maximum yield of 5MU was obtained. The yield of 5MU was 74%, when the initial concentrations of adenosine, thymine, and phosphate were 5 mM each. On the other hand, in the absence of ADA or XOD the yield of 5MU was 1.8%. Several kinds of nucleosides were also synthesized with high yield by the same method.
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PMID:Enzymatic Synthesis of 5-Methyluridine from Adenosine and Thymine with High Efficiency. 2728 Jun 51