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

Enzyme activities were studied in peripheral blood lymphocytes from patients infected with, or at risk for, infection with human immunodeficiency virus (HIV). No significant differences were observed in the HIV-infected and HIV-seronegative high-risk patients with regard to enzyme activities of hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) and purine nucleoside phosphorylase (EC 2.4.2.1) in peripheral blood. Adenosine deaminase (EC 3.5.4.4) was significantly (P less than 0.02) depressed in asymptomatic HIV-seropositive patients and HIV-seronegative patients at high risk of HIV infection as compared with a healthy HIV-seronegative population. Adenosine kinase (AK, EC 2.7.1.20) was significantly increased in the asymptomatic seropositive (P less than 0.02) and also in the HIV-seronegative high-risk groups (P = 0.01) compared with the normal controls. AK activity was significantly lower in subjects with AIDS than in the asymptomatic (P less than 0.002) and high-risk groups (P less than 0.01). Taken together, these results indicate that adenosine deaminase and AK activities are influenced by the health of the patient, and that measurement of AK activity may prove useful in monitoring the clinical progress of patients with HIV infection.
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PMID:Depressed activities of purine enzymes in lymphocytes of patients infected with human immunodeficiency virus. 254 31

The activities of purine-metabolizing enzymes, 5'-nucleotidase, adenosine deaminase, and purine nucleoside phosphorylase in microdissected rat nephron segments were measured. The specific activity of 5'-nucleotidase was highest in the proximal tubules and the cortical collecting duct, but low in the glomerulus. In contrast, the highest activity of adenosine deaminase was found in the glomerulus. The distribution pattern of purine nucleoside phosphorylase was similar to that of adenosine deaminase. These results suggest that various nephron segments can form adenosine and that the glomerulus exhibits highest capacities to metabolize this nucleoside.
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PMID:Intranephron distribution of purine-metabolizing enzymes in rats. 256 Feb 34

2,6-Diaminopurine (DAP) and 2,6-diaminopurine 2'-deoxyriboside (DAPdR) are analogs of adenine and deoxyadenosine, respectively. It was the purpose of this study to compare these analogs under identical conditions in order to define their inhibitory properties and the underlying mechanism in L1210 mouse leukemia cells. In a 5-day cell growth experiment, DAP exerted a significantly stronger antiproliferative effect than DAPdR. Correspondingly, colony formation of L1210 cells in soft agarose was inhibited by DAP to a greater extent than by DAPdR. A differential distribution of L1210 cells in the cell cycle resulted from an exposure to DAP and DAPdR. While DAPdR arrested cells in the G1/G0 phase of the cell cycle, DAP appeared to lead to an accumulation of G2/M cells. The diaminopurines were combined with modulatory agents to test the antiproliferative action of the combinations. Deoxycytidine partially rescued the cells from the growth inhibitory action of DAPdR without affecting the growth of DAP-treated cells. When adenine was used, the antiproliferative effect of DAPdR was slightly enhanced while the effect of DAP was completely abolished. 8-Aminoguanosine, a specific inhibitor of purine nucleoside phosphorylase, synergistically potentiated the cytostatic effect of DAPdR. However, this inhibitor did not alter DAP effects. At the biochemical level, the target of DAPdR was ribonucleotide reductase which was in line with a drastic expansion of the dGTP pool in DAPdR-treated cells. In cells exposed to DAP, high levels of DAP riboside triphosphate were measured; concomitantly, the ATP level dropped markedly. Enzymological studies revealed that DAPdR is an excellent substrate of adenosine deaminase giving rise to the formation of deoxyguanosine. DAP was found to be activated in the purine nucleoside phosphorylase reaction and in a phosphoribosyl-pyrophosphate-dependent reaction. The data from this comparative study suggest that DAPdR and DAP possess different toxicity mechanisms. DAPdR and DAP possess different toxicity mechanisms. DAPdR acts as a precursor of deoxyguanosine, and DAP is metabolically activated to DAP-containing ribonucleotide analogs. These different metabolic routes seem to account for the different effects of DAP and DAPdR at the cellular level.
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PMID:Metabolic activation of 2,6-diaminopurine and 2,6-diaminopurine-2'-deoxyriboside to antitumor agents. 262 71

Estimation of enzymes participating in degradation of purine nucleotides--adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), ecto-5'-nucleotidase as well as the ratio of ADA/PNP in leukocytes was shown to be of importance in differential diagnosis of acute lymphoblast leukosis subforms and for identification of a nature of malignized leukocytes clone in acute undifferentiated leukosis. Importance of these analyses is determined by specific differences in distribution of the enzymatic activity in mononuclear cells in T-, non-T-, non-B-cell acute lymphoblast leukosis and acute myeloblast leukosis as well as due to similar level and ratios of these enzymatic activities in most cases of acute undifferentiated leukosis and in acute lymphoblast leukosis.
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PMID:[Adenosine deaminase, purine nucleoside phosphorylase and ecto-5'-nucleotidase--markers of acute leukemia variants]. 282 93

Different phosphate concentrations were studied for their effect on the degradation of adenosine by rat liver homogenates. It is shown that phosphate considerably inhibits the phosphoribomutase reaction without a significant effect on adenosine deaminase and purine nucleoside phosphorylase activities, that leads to the ribose-1-phosphate accumulation and to the disturbance of nucleoside utilization in reactions of the pentose phosphate pathway. It is supposed that the inhibition of the phosphoribomutase reaction by phosphate is important for regulation of nucleoside and nucleotide formation in a cell.
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PMID:[Phosphate inhibition of the conversion of ribose-1-phosphate--a product of purine nucleoside phosphorylase splitting in the phosphoribomutase reaction]. 282 85

Using radiochemical methods, we determined the activities of various enzymes of purine and pyrimidine metabolism in homogenates of human skeletal muscle and of cultured human muscle cells. Results show a large discrepancy between the enzyme activities in muscle and cultured cells. With regard to purine metabolism, adenylate (AMP) deaminase activity was only 1-3% in cultured cells compared to that in muscle, whereas the activity of adenosine deaminase, purine-nucleoside phosphorylase, adenosine kinase, adenine phosphoribosyltransferase and hypoxanthine phosphoribosyltransferase was 7-15-fold higher in the cultured cells. The enzymes of pyrimidine metabolism, orotate phosphoribosyltransferase, orotidine 5'-monophosphate decarboxylase and uridine kinase showed activity of 100-200-fold higher in cultured cells than in adult muscle. The differences in enzyme activity are probably related to the low differentiation stage and the absence of contractile activity in the cultured muscle cells. Care must be taken when using these cells as a model for studying purine and pyrimidine metabolism of adult myofibers.
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PMID:Purine and pyrimidine metabolism in human muscle and cultured muscle cells. 283 95

A few enzymes of the purine degradative pathway have proved valuable in diagnosis and treatment of lymphomas and lymphocytic leukemia. Of particular interest are the enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and ecto-5'-nucleotidase (5NT). Intact activities of ADA and PNP have been shown to be vital for lymphoid cells. During development, lymphoid precursors go through remarkable changes in the concentrations of these enzymes and the neoplasms derived from them show a "frozen" biochemical profile similar to the corresponding normal cell of origin. Knowledge of the role of these enzymes has led to the pharmacological use of enzyme inhibitors for the specific treatment of lymphoid neoplasms. This review concerns the enzymatic make-up of normal and neoplastic lymphocytes and exploitation of this knowledge for the treatment of lymphomas. Special emphasis will be put on the clinical use of an ADA-inhibitor, deoxycoformycin.
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PMID:Enzymes of purine metabolism in lymphoid neoplasms, clinical relevance for treatment with enzyme inhibitors. 284 34

The in vitro effect of short-term culture as well as the effect of retinol (ROH), retinoic acid (RA), muramyl dipeptide [( Abu']MDP), lipopolysaccharide (LPS), and gamma interferon (IFN-gamma) on the induction of the purine metabolic enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'nucleotidase (5NT) in human peripheral blood monocytes (HPBM) was examined. HPBM isolated by centrifugal elutriation were cultured for up to 96 h. Following an initial time lag of 24 h, mean ADA activity from seven separate experiments as measured in nmoles/10(6) cells/h increased from a baseline of 31.3 +/- 9.3 to 57.8 +/- 16.4 (P less than 0.005) at 72 h and to 72 +/- 21.5 (P less than .025) by 96 h. 5NT activity increased from a baseline of 2.2 +/- 0.9 to a maximum of 44 +/- 10.1 by 72 h and then declined to 29 +/- 18 (P less than 0.005) by 96 h, while no significant change in PNP activity was observed. HPBM incubated for 3 d with optimal concentrations of LPS, RA, and IFN-gamma had increases in ADA and 5NT activity ranging from three- to 10-fold compared to HPBM cultured in media alone, whereas no effect was observed with ROH and [Abu']MDP. RA, but not ROH, significantly enhanced ADA activity in a monocytic leukemia cell (THP-1) line. Addition of RA or the tumor promoter, phorbol 12-myristic 13-acetate (PMA), to HPBM or THP-1 cells resulted in significant increases in 5NT activity with opposite effects on ADA activity. These findings suggest that the biological mechanisms associated with differentiation in normal and malignant monocytes seem to be related and that the sequence and degree to which the various differentiation agents induce the enzyme elevations are also related to the mechanisms of activation/differentiation.
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PMID:Induction of adenosine deaminase and 5' nucleotidase activity in cultured human blood monocytes and monocytic leukemia (THP-1) cells by differentiating agents. 284 22

The levels of purine enzyme activities were studied in 10 patients with acquired immunodeficiency syndrome (AIDS) or AIDS related complex (ARC) and in 6 healthy individuals with antibodies against human immunodeficiency virus (HIV). All AIDS/ARC patients studied had ecto-5'nucleotidase (ecto-5'NUC) activity in B lymphocytes below the normal range and 4 out of 6 clinically healthy HIV-positive likewise had reduced activity. Increased numbers of activated B lymphocytes were found both in the group of healthy HIV positive individuals and in AIDS/ARC patients. Further studies are needed to define whether the decrease in ecto-5'NUC activity on the B lymphocytes is a result of increased activation of the cells or of a B cell defect. No significant changes were found in ecto-5'NUC levels in T lymphocytes or mononuclear cells (MNC), neither in the group of AIDS/ARC patients nor in the healthy HIV-positive group. Both AIDS/ARC patients and healthy individuals with antibodies against HIV had increased levels of adenosine deaminase (ADA) activity in mononuclear cells, but only in the group of AIDS/ARC patients was the increase significant. No changes were found in purine nucleoside phosphorylase (PNP) activity in the two groups tested. From these investigations of purine enzyme levels and other markers of immune function in both sick and healthy HIV infected individuals we conclude that the observed changes in ecto-5'NUC and ADA activities in HIV infected patients are not a direct result of the HIV infection but develop early in the course of the disease.
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PMID:Decreased B lymphocyte ecto-5'nucleotidase and increased adenosine deaminase in mononuclear cells from patients infected with human immunodeficiency virus. 284 68

Activities of the enzymes, responsible for degradation of purine nucleotides in leukocytes, were distinctly dissimilar in M1, M2, M4 and M6 variants of acute non-lymphoblastic leukosis studied in 34 patients. Differentiation of leukemic cells was shown to be due to alterations in activity of adenosine deaminase and purine nucleoside phosphorylase, which were oppositely directed as compared with those observed in lymphoblasts under conditions of acute lymphoblast leukosis. Evaluation of activities of adenosine deaminase, purine nucleoside phosphorylase and 5'-nucleotidase is of importance for characteristics of individual variants of acute non-lymphoblastic leukosis and for elucidation of the state of leukemic clone differentiation, which may affect the efficiency of the therapeutic measures used.
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PMID:[Degradation of purines in leukocytes in acute nonlymphoblastic leukemias]. 285 90


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