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)

Peripheral blood, bone marrow and/or lymph nodes of 77 patients with T- and B-ALLs/lymphomas were characterized for their surface membrane marker profiles using flow cytometry and fluorescence microscopy. Purine metabolism enzyme activities were compared with membrane immunophenotypes. T and B-ALLs/lymphomas subtypes were defined by the expression of surface membrane antigens detected by the monoclonal antibodies. Based on immunophenotyping we found the following characteristic marker profiles: in T-ALL-CD7, CD2, CD1, CD5, CD3, CD4, CD8, CD38, CD71; in T-NHL-CD7,CD2,CD3,CD4,CD5,CD6; in pre-B ALL-CD10, CD19, CD24, HLA-DR, CD34, in B-ALL-CD19, CD20, CD24, HLA-DR, SmIg with kappa or lamda light chains; in B-ALL-weak SmIg, kappa or lambda, CD19, CD20, CD24, CD5, HLA-DR; in B-NHL-CD19, CD20, CD22, CD24, CD5, more intensive SmIg, kappa or lambda. The cells of leukemic cases tended to have more immature phenotypes than those of lymphoma cases. Analysis of purine metabolism enzyme activities showed that there was a correlation between the values of adenosine deaminase (ADA) and purine nucleoside (PNP) and various types of T- and B-ALLs/lymphomas. ADA levels in B-NHL and B-CLL were lower than those in normal cells, while ADA level in T-ALL, T-NHL, pre-B-ALL and B-ALL was higher (the average 185,92,73,63 pkat. 10(-6)cells, respectively). ADA activity was significantly different between lymphocytes of control group and T-ALL(p<0.01), between T-ALL and T-NHL(p<0.05), between T-NHL and B-NHL(p<0.05) and between T-ALL and B-NHL(p<0.05). PNP activities were lower to those in normal cells. ADA/PNP ratio increased mostly in T-ALL, less in T-NHL, pre-B-ALL and B-ALL (10.8 and 5.3 and 2.2, and 2.0 respectively). ADA/PNP ratio was significantly different between T-ALL and pre-B-ALL(p<0.05) and between T-ALL and B-NHL(p<0.05).
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PMID:A comparison of some leucocyte differentiation markers and the adenosine deaminase and purine nucleoside phosphorylase values in B and T cell leukemias and lymphomas. 859 72

The pool of free purine derivatives and activities of the key enzymes of purine metabolism (adenosine deaminase, purine nucleoside phosphorylase, and 5'-nucleotidase) in lymphocytes, erythrocytes, and epidermis homogenates were measured in 20 normal subjects and 15 patients with psoriasis by high-performance liquid chromatography. The levels of AMP, GMP, and IMP purine monophosphates are decreased in the epidermis and red cells of psoriasis patients, whereas the final products of hypoxanthine, xanthine, and uric acid metabolism are accumulating, and the activities of ADA and PNP are increased double in the skin, all this indicating purine derivatives catabolism.
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PMID:[Metabolism of purine compounds in psoriasis]. 957 24

Purine nucleoside phosphorylase had previously been engineered to accept 6-amino substituted purine nucleosides by two active site substitutions, Asn243Asp; Lys244Gln. In the present study, recombinant adenosine phosphorylase (AP) has been conjugated to branched polyethylene glycol (PEG) polymers of approximately 42.5 kDa. Matrix-assisted laser desorption/ionization analysis and SDS acrylamide electrophoresis analysis indicated a subunit composition of greater than 205 kDa consistent with the conjugation of as many as four PEG molecules per AP subunit. The PEG-conjugated enzyme retained greater than 90% of the native catalytic activity. Administration of the enzyme to mice demonstrated the PEG-AP to have a 67-fold increased plasma half-life compared to the native enzyme, 65.1+/-2.9 h versus 57.8+/-1.1 min, respectively. PEG-AP was principally confined to the plasma with minimal activity detected in tissues and of these spleen had the greatest activity and essentially no activity was found in urine. PEG-AP has retained activity with inosine and its injection into PNP-deficient mice resulted in a 2.7-fold increase in urine urate. AP was also shown to protect human CEM cells in culture from the toxic effects of 2'-deoxyadenosine. These studies provide evidence for consideration of PEG-AP as an alternative enzyme therapy for the inherited deficiency of adenosine deaminase.
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PMID:Polyethylene glycol-conjugated adenosine phosphorylase: development of alternative enzyme therapy for adenosine deaminase deficiency. 1263 6

Human malaria infections resulting from Plasmodium falciparum have become increasingly difficult to treat due to the emergence of drug-resistant parasites. The P. falciparum purine salvage enzyme purine nucleoside phosphorylase (PfPNP) is a potential drug target. Previous studies, in which PfPNP was targeted by transition state analogue inhibitors, found that those inhibiting human PNP and PfPNPs killed P. falciparum in vitro. However, many drugs have off-target interactions, and genetic evidence is required to demonstrate single target action for this class of potential drugs. We used targeted gene disruption in P. falciparum strain 3D7 to ablate PNP expression, yielding transgenic 3D7 parasites (Deltapfpnp). Lysates of the Deltapfpnp parasites showed no PNP activity, but activity of another purine salvage enzyme, adenosine deaminase (PfADA), was normal. When compared with wild-type 3D7, the Deltapfpnp parasites showed a greater requirement for exogenous purines and a severe growth defect at physiological concentrations of hypoxanthine. Drug assays using immucillins, specific transition state inhibitors of PNP, were performed on wild-type and Deltapfpnp parasites. The Deltapfpnp parasites were more sensitive to PNP inhibitors that bound hPNP tighter and less sensitive to MT-ImmH, an inhibitor with 100-fold preference for PfPNP over hPNP. The results demonstrate the importance of purine salvage in P. falciparum and validate PfPNP as the target of immucillins.
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PMID:Plasmodium falciparum purine nucleoside phosphorylase is critical for viability of malaria parasites. 1895 39


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