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)

Activities of adenosine deaminase (ADA), adenosine kinase (AK), adenine phosphoribosyltransferase (APRT), hypoxanthine guanine phosphoribosyltransferase (HGPRT), and purine nucleoside phosphorylase (PNP), all enzymes of the purine interconversion system, were determined in lymphocytes of 25 patients with chronic lymphatic leukemia (CLL) and in 23 controls. A statistically significant decrease of PNP activities and a reduction of ADA activities at borderline levels were found in the patients, whereas for the other enzymes assayed no deviation from normal values was observed.
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PMID:Enzymes of the purine interconversion system in chronic lymphatic leukemia: decreased purine nucleoside phosphorylase and adenosine deaminase activity. 11 97

Model studies with gene transfer technology using retroviral vectors expressing the cloned human genes for adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and hypoxanthine guanine phosphoribosyltransferase (HPRT) indicate that these disorders may eventually be treated by the introduction of the normal gene into defective cells. The autologous transplantation of bone marrow infected in vitro with retroviral vectors is the most developed approach at this time. The potential usefulness of this and other approaches for each of these three disorders of purine metabolism are discussed.
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PMID:Approaches to gene therapy in disorders of purine metabolism. 305 Nov 60

The mechanism by which 2'-deoxyguanosine is toxic for lymphoid cells is relevant both to the severe cellular immune defect of inherited purine nucleoside phosphorylase (PNP) deficiency and to attempts to exploit PNP inhibitors therapeutically. We have studied the cell cycle and biochemical effects of 2'-deoxyguanosine in human lymphoblasts using the PNP inhibitor 8-aminoguanosine. We show that cytostatic 2'-deoxyguanosine concentrations cause G1-phase arrest in PNP-inhibited T lymphoblasts, regardless of their hypoxanthine guanine phosphoribosyltransferase status. This effect is identical to that produced by 2'-deoxyadenosine in adenosine deaminase-inhibited T cells. 2'-Deoxyguanosine elevates both the 2'-deoxyguanosine-5'-triphosphate (dGTP) and 2'-deoxyadenosine-5'-triphosphate (dATP) pools; subsequently pyrimidine deoxyribonucleotide pools are depleted. The time course of these biochemical changes indicates that the onset of G1-phase arrest is related to increase of the dATP rather than the dGTP pool. When dGTP elevation is dissociated from dATP elevation by coincubation with 2'-deoxycytidine, dGTP does not by itself interrupt transit from the G1 to the S phase. It is proposed that dATP can mediate both 2'-deoxyguanosine and 2'-deoxyadenosine toxicity in T lymphoblasts.
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PMID:Deoxyadenosine triphosphate as a mediator of deoxyguanosine toxicity in cultured T lymphoblasts. 349 Apr 93

The thermostability of erythrocyte hypoxanthine guanine phosphoribosyltransferase of 2 Werner's syndrome patients was compared with that of normal subjects of different ages. No significant difference was observed regarding the thermal stability of the enzyme among normal subjects and Werner's syndrome patients. The activities of other erythrocyte enzymes, phosphoribosylpyrophosphate synthetase, adenine phosphoribosyltransferase, adenosine deaminase and purine nucleoside phosphorylase, were similar between Werner's syndrome and normal subjects.
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PMID:Normal thermostability of hypoxanthine guanine phosphoribosyltransferase in erythrocytes from Werner's syndrome patients. 377 Apr 88

Some purine metabolizing enzymes of lymphocytes and granulocytes were determined in 13 patients with cirrhosis of the liver and in a control group consisting of 18 healthy blood donors. Furthermore cytidine deaminase (EC 3, 5, 4, 5) (CRD) activity was determined in the granulocytes of these patients and in 16 controls. An increase of adenosine deaminase (EC 3, 5, 4, 4) (ADA) activity was found in granulocytes (P less than 0.01) as well as in lymphocytes (P less than 0.01) of the cirrhotic patients as compared to controls. Purine nucleoside phosphorylase (EC 2, 4, 2, 1) (PNP) activity in granulocytes and lymphocytes was identical in the two groups. In lymphocytes of cirrhotic patients decreased hypoxanthine guanine phosphoribosyltransferase (EC 2, 4, 2, 8) (HGPRT) (P less than 0.01), adenine phosphoribosyltransferase (EC 2, 4, 2, 7) (APRT) (P less than 0.02) and adenosine kinase activities (EC 2, 7, 1, 20) (AK) (P less than 0.05) were demonstrated. 5'-nucleotidase (5'-N (EC 3, 1, 3, 5) activity in lymphocytes of cirrhotic patients was slightly increased, the increase being correlated to the level of serum gamma globulin. Granulocytes from cirrhotic patients showed a decrease of CRD (P less than 0.05). The finding that ADA activity is increased in mature lymphocytes and granulocytes from cirrhotic patients argues against the possibility that increase of lymphocytes ADA activity is a consequence of malignant transformation or immaturity.
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PMID:Changes in some nucleoside metabolizing enzymes of lymphocytes and granulocytes from patients with cirrhosis of the liver. 641 76

The metabolism of 8-14C-labelled 2'-deoxyadenosine (dAR) and 2'-deoxyguanosine (dGR) has been investigated using lymphocytes in long-term culture transformed by Epstein-Barr (EB) virus (B-cells) from eight patients with different inherited purine enzyme defects. The use of such lines enabled accurate mapping of the route of metabolism by acting as a 'trap' for the radiolabel at specific points. With either substrate (25 microM) most of the label was recovered in the medium. Using dAR, less than 30% of the radiolabel was incorporated into cellular nucleotides. For dGR, values were less than 18%. Studies with dAR alone confirmed the principal route of metabolism was to hypoxanthine, with further metabolism (by lines with intact salvage pathways) to ATP and GTP in the ratio of approximately 4:1. Lack of accumulation of deoxyinosine in the purine nucleoside phosphorylase (PNP) deficient line, or hypoxanthine in the hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficient line, using dAR together with the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) at 10 microM, confirmed the effectiveness of ADA inhibition. Nevertheless, some ATP was still formed by all lines in the presence of dCF by a route as yet unknown. Only the ADA deficient lines formed dATP with dAR alone. However, some dATP was formed by all lines in the presence of dCF. A partially HGPRT deficient line formed extremely high dATP levels, well in excess of those formed by the T-cell line CEM. Studies with dGR revealed some interesting differences, a large proportion of the substrate being metabolized predominantly to xanthine by most enzyme deficient lines. In the PNP deficient line most of the substrate remained unmetabolized, but some dGTP was formed. No other enzyme deficient line formed any dGTP--with or without the PNP inhibitor 8-aminoguanosine (8-NH2GR)--with one exception. Again this was the partially HGPRT deficient line, which with the inhibitor again formed more dGTP than the T-cell line. Within the cells most of the substrate was metabolized to GTP, except in the PNP, and totally HGPRT deficient lines. Levels of GTP formed were not altered by the inhibitor, reflecting the lack of effective PNP inhibition by 8-NH2GR. Some counts were also found in ATP and IMP, confirming the existence of this route in mammalian cells of lymphoid origin. The results also support previous studies by us using cell lines with intact purine pathways, which demonstrated that, contrary to current beliefs, some B-cell lines are capable of accumulating high levels of deoxynucleotides.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Metabolism of deoxynucleosides by lymphocytes in long-term culture deficient in different purine enzymes. 642 79

Pathways producing and converting adenosine have hardly been investigated in human heart, contrasting work in other species. We compared the kinetics of enzymes associated with purine degradation and salvage in human and rat heart cytoplasm assaying for adenosine deaminase, nucleoside phosphorylase, xanthine oxidoreductase, AMP deaminase, AMP- and IMP-specific 5'-nucleotidases, adenosine kinase and hypoxanthine guanine phosphoribosyltransferase (HGPRT). Xanthine oxidoreductase was not detectable in human heart. The Km-values of the AMP-catabolizing enzymes were 2-5 times higher in human heart; the substrate affinity of the other enzymes was in the same order of magnitude in both species. The maximal activity (Vmax) of adenosine kinase was the same in both species, but HGPRT in man was only 12% of that in the rat. For human heart the Vmax-values of adenosine deaminase, nucleoside phosphorylase, AMP- and IMP-specific 5'-nucleotidases, and AMP deaminase were 25-50% of those for rat heart. We conclude that human heart is less geared to purine catabolism than rat heart as is evident from the lower activities of the catabolic enzymes. Maintenance of the nucleotide pool may thus play a more important role in human heart.
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PMID:Kinetics of adenylate metabolism in human and rat myocardium. 759 55

A large series of samples obtained after surgical resection of intestinal mucosa of patients affected by intestinal carcinoma was examined in order to define possible relationships between levels of enzymes involved in the purine salvage pathway and clinical/biological parameters of aggressiveness and invasiveness. The results confirm our previous observation on a different pattern of purine salvage enzymes in tumor as compared to normal colon tissues (Camici et al., 1990). In fact, we observed in human colon tumor tissues a significant enhancement of the three enzymes involved in the synthesis of IMP, hypoxanthine guanine phosphoribosyltransferase (HGPRT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP). On the other hand, no variation was observed in the 5'-nucleotidase and alkaline phosphatase activities. While we could not find a significant correlation between HGPRT, ADA and PNP activities and histologic grading or biological parameters of tumor aggressiveness, the significant correlation with the extent of disease, as expressed by the Dukes' stage, would demonstrate at least for human colon tumors, a relationship between enzyme activity and tumor invasiveness.
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PMID:Relationship between the levels of purine salvage pathway enzymes and clinical/biological aggressiveness of human colon carcinoma. 779 89

To determine whether interferon-gamma affects rat purine catabolic and salvage enzyme activities, rats were injected with interferon-gamma (600000 U/kg, i.p.) and, similarly to a vehicle-injected control group, killed before or after injection at 6, 12, and 24 h. Organ homogenates were prepared and enzymatic reactions with substrates were carried out, after which the products were measured either chromatographically or spectrophotometrically. Western and Northern blotting also were performed. In contrast to the vehicle-injected rats, interferon-gamma-injected rats showed a significant rise in xanthine oxidoreductase activity in the liver, while enzyme activity was unchanged in the spleen, kidney, and lung. Western analysis of hepatic xanthine oxidoreductase showed an increased concentration of this protein 12 and 24 h after interferon-gamma injection. Northern analysis disclosed an enhanced mRNA expression coding for this enzyme, peaking 12 h after injection. Contrastingly, the activities of adenosine deaminase, purine nucleoside phosphorylase, hypoxanthine guanine phosphoribosyltransferase, and adenine phosphoribosyltransferase were not affected by interferon-gamma in any organ tested. While interferon-gamma causes an increased hepatic biosynthesis of xanthine oxidoreductase, the physiologic role of this enzyme induction remains undetermined.
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PMID:Effect of interferon-gamma on purine catabolic and salvage enzyme activities in rats. 1035 Jun 54

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


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