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)

A genetic deficiency of purine nucleoside phosphorylase (NP) is associated with immune dysfunctin that specifically affects T cells. An absence of adenosine deaminase (ADA), the preceding enzyme in the pathway of purine recycling, is associated with failure of both T and B lymphocyte function. Formycin B, an analogue of inosine and an inhibitor of purine nucleosidase phosphorylase, was used in cell culture systems to stimulate deficiency of this enzyme. The cells used were normal circulating lymphocytes and lymphoblastoid cell lines (LCL) with T and B cell characteristics. Formycin B inhibited the growth of these cells, but its primary effect was found to be due to a mechanism other than purine nucleoside phosphorylase inhibition. The possibility that formycin B was inhibiting adenosine deaminase, for which it is a product analogue, was studied by the analysis of reaction progress curves using the integrated rate equation. The molecular structure of formycin B, whilst preventing its phosphorylytic cleavage by purine nucleoside phosphorylase, could enable this compound to function as a substrate for adenosine kinase. The resultant formation of formycin B nucleotide probably causes the observed inhibition of growth in cultured cells.
 ...
PMID:Formycin B, purine nucleoside phosphorylase and lymphocyte function. 677 48

Adenosine, through activation of membrane-bound receptors, has been reported to have neuroprotective properties during strokes or seizures. The role of astrocytes in regulating brain interstitial adenosine levels has not been clearly defined. We have determined the nucleoside transporters present in rat C6 glioma cells. RT-PCR analysis, (3)H-nucleoside uptake experiments, and [(3)H]nitrobenzylthioinosine ([(3)H]NBMPR) binding assays indicated that the primary functional nucleoside transporter in C6 cells was rENT2, an equilibrative nucleoside transporter (ENT) that is relatively insensitive to inhibition by NBMPR. [(3)H]Formycin B, a poorly metabolized nucleoside analogue, was used to investigate nucleoside release processes, and rENT2 transporters mediated [(3)H]formycin B release from these cells. Adenosine release was investigated by first loading cells with [(3)H]adenine to label adenine nucleotide pools. Tritium release was initiated by inhibiting glycolytic and oxidative ATP generation and thus depleting ATP levels. Our results indicate that during ATP-depleting conditions, AMP catabolism progressed via the reactions AMP --> IMP --> inosine --> hypoxanthine, which accounted for >90% of the evoked tritium release. It was surprising that adenosine was not released during ATP-depleting conditions unless AMP deaminase and adenosine deaminase were inhibited. Inosine release was enhanced by inhibition of purine nucleoside phosphorylase; ENT2 transporters mediated the release of adenosine or inosine. However, inhibition of AMP deaminase/adenosine deaminase or purine nucleoside phosphorylase during ATP depletion produced release of adenosine or inosine, respectively, via the rENT2 transporter. This indicates that C6 glioma cells possess primarily rENT2 nucleoside transporters that function in adenosine uptake but that intracellular metabolism prevents the release of adenosine from these cells even during ATP-depleting conditions.
 ...
PMID:Purine uptake and release in rat C6 glioma cells: nucleoside transport and purine metabolism under ATP-depleting conditions. 1098 33