Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The effects of S-adenosylhomocysteine and S-adenosylmethionine on some purine- and pyrimidine-metabolizing systems have been examined. Both compounds were capable of acting as relatively good inhibitors of adenosine deaminase, nucleoside phosphorylase, and adenylate deaminase activities but as relatively poor inhibitors of myokinase and nucleoside monophosphate kinase. The inhibitory effects were freely reversible. 5'-Nucleotidase, orotidine 5'- phosphate, and phosphodiesterase were unaffected. Nucleoside phosphorylase was competitively inhibited by both compounds, whereas mixed inhibitory effects occurred with adenosine deaminase.
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PMID:The effects of S-adenosylhomocysteine and S-adenosylmethionine on some purine- and pyrimidine-metabolizing systems. 629 1

Two novel halogenated pyrrolopyrimidine analogues of adenosine, isolated from marine sources, have been examined for pharmacological and biochemical activities. 4-Amino-5-bromo-pyrrolo[2,3-d]pyrimidine, from a sponge of the genus Echinodictyum, had bronchodilator activity at least as potent as theophylline but with a different biochemical profile; unlike theophylline it had no antagonist activity at CNS adenosine receptors and it was quite a potent inhibitor of adenosine uptake and adenosine kinase in brain tissue. 5'-Deoxy-5-iodotubercidin, isolated from the red alga Hypnea valentiae, caused potent muscle relaxation and hypothermia when injected into mice. This compound was a very potent inhibitor of adenosine uptake into rat and guinea-pig brain slices and an extremely potent inhibitor of adenosine kinase from guinea-pig brain and rat brain and liver. Neither of these two pyrrolopyrimidine analogues was a substrate for, or an inhibitor of, adenosine deaminase. Neither compound appeared to have any direct agonist activity on guinea-pig brain adenosine-stimulated adenylate cyclase (A2 adenosine receptors). 5'-Deoxy-5-iodotubercidin is unique in two respects: it appears to be the first naturally-occurring example of a 5'-deoxyribosyl nucleoside and is the first example of a specifically iodinated nucleoside from natural sources. It may be the most potent adenosine kinase inhibitor yet described and, by virtue of its structure, may prove to be the most specific.
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PMID:Halogenated pyrrolopyrimidine analogues of adenosine from marine organisms: pharmacological activities and potent inhibition of adenosine kinase. 632

We have investigated the specificity of the tRNA modifying enzyme that transforms the adenosine at position 34 (wobble position) into inosine in the anticodon of several tRNAs. For this purpose, we have constructed sixteen recombinants of yeast tRNAAsp harboring an AXY anticodon (where X or Y was one of the four nucleotides A, G, C or U). This was done by enzymatic manipulations in vitro of the yeast tRNAAsp, involving specific hydrolysis with S1-nuclease and RNAase A, phosphorylation with T4-polynucleotide kinase and ligation with T4-RNA ligase: it allowed us to replace the normal anticodon GUC by trinucleotides AXY and to introduce simultaneously a 32P-labelled phosphate group between the uridine at position 33 and the newly inserted adenosine at position 34. Each of these 32P-labelled AXY "anticodon-substituted" yeast tRNAAsp were microinjected into the cytoplasm of Xenopus laevis oocytes and assayed for their capacity to act as substrates for the A34 to I34 transforming enzyme. Our results indicate that: 1/ A34 in yeast tRNAAsp harboring the arginine anticodon ACG or an AXY anticodon with a purine at position 35 but with A, G or C but not U at position 36 were efficiently modified into I34; 2/ all yeast tRNAAsp harboring an AXY anticodon with a pyrimidine at position 35 (except ACG) or uridine at position 36 were not modified at all. This demonstrates a strong dependence on the anticodon sequence for the A34 to I34 transformation in yeast tRNAAsp by the putative cytoplasmic adenosine deaminase of Xenopus laevis oocytes.
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PMID:Enzymatic conversion of adenosine to inosine in the wobble position of yeast tRNAAsp: the dependence on the anticodon sequence. 636 51

The purine metabolism of four cases with marked hypouricemia (serum uric acid concentration of less than 0.018 mmol/l) from three Japanese families was investigated. Erythrocyte adenosine deaminase (EC 3.5.4.4) and purine-nucleoside phosphorylase (EC 2.4.2.1) activities of the patients were within the normal ranges. Urinary hypoxanthine and xanthine concentrations were 0.096-0.397 mmol/l and 0.743-1.717 mmol/l, respectively. Xanthine oxidase (EC 1.2.3.2) activities in the jejunal mucosa of the two normal controls were 0.257 and 0.283 units/g protein, while those of three of the patients were extremely low and could not be determined. The findings of these biochemical features may indicate that the four patients have hereditary xanthinuria. In order to study the purine metabolism in the hypouricemic condition of this disorder, a single oral dose of allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) was administered in one case. The excretion pattern of allopurinol and oxypurinol (4,6-dihydroxypyrazolo[3,4-d]pyrimidine) in the urine of the patient was similar to that of a normal control male. These data suggest that some residual enzyme activity may be functioning in vivo, although the presence of xanthine oxidase could not be detected.
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PMID:Biochemical studies on the purine metabolism of four cases with hereditary xanthinuria. 642 23

The levels of the purine catabolic enzymes, adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP), together with the pyrimidine activities, thymidine phosphorylase (TP) and thymidine kinase isozymes (TK) have been determined for cells obtained from solid lymphoid tissue of 38 patients with non-Hodgkin's lymphoma (NHL) and 14 individuals exhibiting benign reactive lymphoid hyperplasia. Within each NHL histological group subtyped according to the Rappaport classification, and in the reactive hyperplasia group, there was considerable variation in these activities. However, higher levels of TK and TP activities occurred in cells of the histologically unfavourable prognostic NHL groups compared with those of favourable histology or reactive hyperplasia. There was an inverse relationship between survival and elevated TK isozyme 1 and TP levels, which was independent of histological classification and clinical staging. These results indicate that, in addition to morphology, estimations of TK and TP of involved lymphoma cells in NHL is of clinical relevance.
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PMID:Pyrimidine and purine activities in non-Hodgkin's lymphoma. Correlation with histological status and survival. 642 90

Neoplastic lymphocytes from a horse with lymphosarcoma and IgM deficiency were analyzed for ability to grow in culture; surface and cytoplasmic IgM; functional activity in blastogenesis, cytoxicity, and suppressor assays; and activities of six enzymes involved in purine and pyrimidine metabolism. The cells lacked surface and cytoplasmic IgM. They had elevated activity of adenosine deaminase and reduced activity of purine nucleoside phosphorylase. Neoplastic cells were nonresponsive in blastogenesis assay and did not kill allogeneic lymphocyte target cells or YAC-1 targets in a lectin-dependent cytotoxicity assay, however, the cells were active in a suppressor assay. They were grown for 16 weeks in cultures supplemented with interleukin 2, during which time the cells retained suppressive activity. These results are consistent with a T cell lymphoma of suppressor cell origin, and may explain the deficiency of IgM observed in some horses with lymphoreticular neoplasms.
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PMID:Biochemical and functional characterization of lymphocytes from a horse with lymphosarcoma and IgM deficiency. 654 49

Biosynthesis of purine and pyrimidine nucleotides was distinctly increased in leukocytes of patients with chronic myeloid leukosis, involving mainly the reutilization of preformed nitrogenous bases and nucleosides. An increase in the rate of 14C-orotate and 3H-uridine incorporation into the pyrimidine pool of myeloid leukosis cells correlated with stimulation of uridine kinase and orotidine monophosphate pyrophosphorylase, catalyzing biosynthesis of pyrimidine nucleotides in the reutilization pathway and de novo, respectively. The system of adenosine deaminase, providing the high rate of adenosine incorporation into the nucleotide pool, was apparently responsible mainly for the rate of reutilization synthesis of purine nucleotides in normal and leukemic leukocytes. Synthesis of RNA in leukocytes of patients with chronic myeloleukemia was increased mainly due to consumption of nucleotides formed via the reutilization pathway.
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PMID:[Metabolism of nucleotides and RNA in leukocytes in chronic myeloleukosis]. 657 34

Structural analogues of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), in which the adenine moiety of the molecule was modified, were prepared in order to investigate the structural requirement of EHNA as an inhibitor of adenosine deaminase (ADA). Thus, 1- and 3-deaza-EHNA and their 6-deamino analogues were synthesized and evaluated as inhibitors of ADA from calf intestine. Inhibition studies indicated that isosteric substitution of pyrimidine nitrogens by carbons could be tolerated at the enzymatic binding site. In fact, 3-deaza-EHNA was found to have an inhibitory activity comparable to EHNA itself, and 1-deaza-EHNA, though less potent, is a good inhibitor. The 6-amino group gives an important contribution to the enzymatic binding if the N1 nitrogen is also present, conferring on the compound the characteristic of a semitight inhibitor.
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PMID:Adenosine deaminase inhibitors. Synthesis of deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine. 669 73

In experiments with mongrel male rats the asparaginase and adenosine deaminase activities in the liver tissue and adenosine deaminase in blood serum were determined under different conditions of parenteral nutrition. The intraperitoneal administration of the preparations of parenteral nitrogen nutrition-aminosol and amikin (0.25 g of conditioned protein per 100 g of body weight) against a background of protein deficiency and exhaustion is shown to cause no changes as compared to the control of these enzymes activity in the liver tissue and blood serum. The asparaginase activity in the liver increases noticeably with the dose of aminosol and amikin up to 0.5 g of conditioned protein per 100 g of body weight and the adenosine deaminase activity undergo no essential changes. A statistically significant decrease in the adenosine deaminase activity is observed only under administration of aminosol against a background of protein deficiency. Under oral feeding of rats with amikin in the composition of protein-free (0.5 g of conditioned protein per 100 g of body weight), as distinct from its parenteral administration, the asparaginase activity in the liver is considerably lower. The adenosine deaminase activity in the liver and blood serum is not practically changed. A part of the nitrogen excreted from the organism with urea and ammonia under protein deficiency is supposed to be a product of deamination of endogenic purine and pyrimidine derivatives.
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PMID:[Dynamics of asparaginase and adenosine deaminase activity in the liver with intraperitoneal administration of aminosol and amikin preparations of parenteral nitrogen nutrition]. 680 84

The cellular levels of the purine catabolic enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and those for the pyrimidine activities thymidine phosphorylase and thymidine kinase isozymes have been measured concurrently in peripheral blood nucleated cells of patients with acute lymphoblastic leukaemia, chronic lymphocytic or prolymphocytic leukaemia and correlated with the spontaneous tritiated thymidine uptake of the isolated cells. Highest ADA levels occurred in T-ALL cells but considerable overlap of individual activities occurred for non-T, non-BALL, B-CLL and T-CLL cells. The levels of PNP showed no distinct discriminatory trend in cells of the lymphoid proliferative disorders examined. Thymidine phosphorylase activity was markedly reduced in T-ALL and T-CLL cells with a stepwise increase in the level of mean activities for non-T, non-B ALL, B-CLL and B-PLL cells to that of isolated normal peripheral blood lymphocytes. Spontaneous tritiated thymidine uptake of the abnormal lymphoid cells exhibited a correlation between cellular thymidine kinase isozyme 1 and elevated ADA levels. The use of ADA inhibitors together with thymidine infusion for the treatment of lymphoproliferative disorders is discussed.
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PMID:Purine and pyrimidine activities in acute and chronic lymphocytic leukaemia: relation to cellular proliferative status. 681 8


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