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 antiproliferative activity of 9-beta-D-arabinofuranosyladenine 5'-monophosphate against a cultured line of mouse leukemia cells (L1210/C2) was enhanced by addition of either 2'-deoxycoformycin or erythro-9-(2-hydroxy-3-nonyl)adenine. The activity of 9-beta-D-arabinofuranosyladenine 5'-monophosphate, alone or in combination with either of the two inhibitors of adenosine deaminase, was comparable to that of 9-beta-D-arabinofuranosyladenine (ara-A), apparently reflecting the rapid conversion of 9-beta-D-arabinofuranosyladenine 5'-monophosphate to ara-A by L1210/C2 cells. Several ara-A analogs were assayed for antiproliferative activity against L1210/C2 cells; of these, only 9-beta-D-arabinofuranosyladenine 5'-O-methylphosphate and 2'-deoxy-2'-amino-9-beta-D-arabinofuraosyladenine were active. Addition of 2'-deoxycoformycin to cell culture fluids enhanced the activity of 9-beta-D-arabinofuranosyladenine 5'-O-methylphosphate suggesting conversion to an adenosine deaminase-sensitive intermediate, presumably ara-A.
Cancer Res 1979 May
PMID:Antiproliferative effects of 9-beta-D-arabinofuranosyladenine 5'-monophosphate and related compounds in combination with adenosine deaminase inhibitors against mouse leukemia L1210/C2 cells in culture. 8 84

Purine metabolism and reutilization pathways were studied as they applied to normal and leukemic leukocytes. The enzyme activities were expressed in terms of the quantity of protein extracted and per 10(10) cells. Whereas the protein extracted and the enzyme activities from normal lymphocytes were relatively constant, considerable variation was noted in cases of chronic lymphocytic leukemia (CLL). This variability in the properties of the leukemic cells suggests that the difference may be useful in the subclassification of the leukemias. The studies of the complete enzyme system were done with 300 million cells. The extraction of 350,000 normal lymphocytes/mul gave a soluble protein concentration of 1.46+/-0.16 mg protein per ml, and the yield from the same number of CLL lymphocytes varied between 0.72 and 8.32 mg protein per ml. The 5'-nucleotidase activity gave an inverse correlation with the amount of extractable protein. In individual cases of CLL, the protein concentrations and the 5'-nucleotidase activities were found on either side of the normal values. In most cases, the adenosine deaminase of CLL lymphocytic cell extracts was lower than normal, and the adenosine kinase was higher; in the CLL cells, these two enzymes gave a positive correlation with one another. Little or no difference was observed in the activities of the purine nucleoside phosphorylases in extracts of normal or leukemic lymphocytes and granulocytes. The hypoxanthine-guanine and adenine phosphoribosyltransferase activities increased in the leukemic granulocytes but almost always showed a decrease in the CLL lymphocytes when compared with the normal cells. Most of the leukemic cells had greater than normal activities of the enzymes synthesizing phosphoribosyl pyrophosphate when tested with the purines. The total nucleotide produced from adenine and guanine with adenine- and hypoxanthine-guanine phosphoribosyltransferase was about equal in normal and leukemic lymphocytes, but the proportion of the adenosine 5'-triphosphate in the product was much greater with the leukemic cells. This suggested that the ribosyltransferase activities were the same in both types of cells, but the nucleoside kinases and the nucleoside diphosphate kinases were more active in the leukemic cells. Inosine monophosphate dehydrogenase was less active than normal in the CLL cell extracts and was not directly related to the amount of inosine monophosphate generated from hypoxanthine.
Cancer Res 1977 Feb
PMID:Purine metabolic cycle in normal and leukemic leukocytes. 18 45

The search for molecular changes that may be diagnostic of malignancy in the colonic epithelium is complicated by the diversity of cell types and complex cell kinetics of a tissue in which most of the cells are destined to leave within hours or days. Methods for cell separation and nuclear fractionation now permit biochemical studies of those cells that retain or regain the capacity for DNA synthesis and that are likely to include the transformed cell population. Among the changes associated with malignant transformation to be described are alterations in nuclear protein composition and metabolism, qualitative and quantitative differences in adenosine deaminase activities, activation of the guanylate/cyclic GMP system, and modification of both DNA and chromosomal proteins by alkylating carcinogens. DNA modification to produce O6-methylguanine correlates well with the incidence of tumor induction by methylazoxymethanol. Modifications of chromosomal proteins to produce methylated derivatives of lysine and arginine have been observed after the administration of 1,2-dimethylhydrazine. Such changes are likely to lead to aberrant interactions between DNA and regulatory elements in chromatin, and may not be subject to repair.
Cancer 1977 Nov
PMID:Overview: molecular changes associated with large bowel cancer and their potential as markers and chemotherapeutic agents. 20 Mar 43

Adenosine deaminase and adenosine kinase have been measured in rat liver, 12 transplantable hepatomas, regenerating, foetal and neonatal liver, adult and neonatal rat kidney and 2 transplantable kidney tumours. Adenosine, deaminase activity, relative to the normal liver value, was elevated 2-4 fold in hepatomas of rapid growth rate, was in the normal range in more slowly growing hepatomas and in regernerating liver, and was low in foetal and neonatal liver. Adenosine kinase activity was decreased, relative to rat liver values, in all the hepatomas; activity of this enzyme gave a negative correlation with tumour growth rate. Kinetic properties of the two enzymes were examined in partially purified preparations. Adenosine deaminases from both liver and rapidly growing hepatoma 3924A were subject to weak product inhibition by inosine. Adenosine kinase from liver and hepatoma 3924A was inhibited by the reaction products ADP and AMP, and the enzyme was also subject to excess substrate inhibition by concentrations of ATP in excess of 1 mM. In rat hepatoma cell lines growing in culture, the toxicity of adenosine correlated inversely with the ratio of adenosine deaminase activity to adenosine kinase activity. Chromatographic measurements showed that hepatoma cells incorporated less extracellular adenosine into their adenine nucleotide pools than did isolated liver cells. These results indicate that increased adenosine deaminase activity and decreased adenosine kinase activity may confer a selective advantage upon the cancer cell.
Br J Cancer 1978 May
PMID:Adenosine deaminase and adenosine kinase in rat hepatomas and kidney tumours. 20 96

Deoxyadenosine but not adenosine reversed the antiviral activity of 9-beta-D-arabinofuranosyladenine (ara-A) and 9-beta-D-arabinofuranosylhypoxanthine (ara-H) when used in the presence of coformycin, an inhibitor of adenosine deaminase. In suspension cultures of KB cells, 10 muM ara-A inhibited the replication of herpes simplex virus type 1 by 80%. Concomitant addition of 50 muM deoxyadenosine reduced the antiviral activity of 10 muM ara-A to only 40% inhibition. Adenosine failed to antagonize the antiviral activity. In monolayer cultures of KB cells, the 50% inhibitory concentration of ara-A was increased from 1.5 to 2.9 muM by 2 muM deoxyadenosine and to 8.5 muM by 10 muM deoxyadenosine. Analysis of the dose-response data by a double reciprocal plot method indicated that the antagonism was competitive. The antiviral activity of ara-H also was antagonized by deoxyadenosine. The 50% inhibitory concentration of ara-H was increased from 42 muM to 70, 91, or 121 muM by the concurrent addition of 5, 10, or 20 muM deoxyadenosine. Competitive antagonism could not be demonstrated. In the absence of the adenosine deaminase inhibitor, neither ara-A nor ara-H was antagonized by deoxyadenosine. Since such inhibitors were not available unitl recently, previous investigators were unable to observe the antagonistic capacity of deoxyadenosine.
Cancer Res 1978 Jul
PMID:Deoxyadenosine antagonism of the antiviral activity of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosylhypoxanthine. 20 16

The greater in vivo antitumor activity of 4-amino-3-carboxamido-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (APPCR) in comparison to the parent compound 4-amino-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (APPR) may involve intrinsic differences in the effects of these two compounds on cells, as well as in their metabolisms. In studies with L1210 cells in vitro, growth inhibition by APPCR for 36 hr or more was found to be cytocidal, while growth inhibition by APPR was cytostatic in that a substantial fraction of the cells survived 36 or 72 hr of exposure to growth-inhibiting concentrations of APPR. It appears that this difference in the cellular effects of APPCR and APPR is not related to differences in the requirement for activation by phosphorylation or in susceptibility to inactivation by deamination. However, deamination may limit the effectiveness of APPR in vivo since it is a substrate for adenosine deaminase, while deamination of APPCR is not detectable.
Cancer Res 1979 Aug
PMID:Study of the cytotoxicity and metabolism of 4-amino-3-carboxamido-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine using inhibitors of adenosine kinase and adenosine deaminase. 22 42

The growth of cultured L5178Y cells is inhibited by relatively low concentrations fo deoxyadenosine in the presence of deoxycoformycin, an inhibitor of adenosine deaminase. Cell viability is reduced, presumably as a consequence of the induced state of unbalanced growth which is characterized by inhibition in DNA synthesis, accumulation of cells in G1 or early S phase, a continuation in RNA synthesis, and increasing cell volume. The intracellular concentrations of purine and pyrimidine ribonucleoside phosphates remain essentially unchanged. The significant changes in the intracellular deoxynucleoside triphosphate pools are an increase in deoxyadenosine triphosphate and a decrease in deoxycytidine triphosphate.
Cancer Res 1977 Sep
PMID:Deoxyadenosine metabolism and toxicity in cultured L5178Y cells. 30 72

The effect of the adenosine deaminase inhibitor, 2'-deoxycoformycin, on the inhibitory effect of cordycepin on nuclear RNA synthesis was examined in L1210 cells in vitro. The median inhibitory dose for the effect of deoxycoformycin on adenosine deaminase was 4 X 10(-8) M, and 100% inhibition was achieved at 5 X 10(-7) M. Pretreatment of cells for 30 min with 1 X 10(-6) M deoxycoformycin resulted in a reduction of the median inhibitory dose for cordycepin from 2.5 X 10(-4) to 1.8 X 10(-5) M, as assessed by the measurement of [3H]uridine incorporation into total RNA. Measurement of the synthesis of nuclear ribosomal RNA, nonpolyadenylic acid heterogeneous RNA, and polyadenylic acid heterogeneous RNA revealed potentiation by 2'-deoxycoformycin of the inhibitory effect of cordycepin on all species of RNA, as well as on polyadenylic acid synthesis. No differences were noted in the size of nuclear polyadenylic acid obtained from cells treated with cordycepin in either the presence or the absence of the adenosine deaminase inhibitor. These results suggest that the potentiation by 2'-deoxycoformycin of the cytotoxic and antitumor effects of cordycepin on L1210 cells in vivo is related to inhibition of nuclear RNA synthesis.
Cancer Res 1978 Aug
PMID:Potentiation by 2'-deoxycoformycin of the inhibitory effect by 3'-deoxyadenosine (cordycepin) on nuclear RNA synthesis in L1210 cells in vitro. 30 28

The adenosine analogs, 9-beta-D-xylofuranosyladenine (XA) and 3'-deoxyadenosine (cordycepin) were tested for their ability to interfer with S-adenosyl-L-methionine (SAM) formation in L1210 cells in vitro. XA inhibited the incorporation of [3H]methionine into SAM in a mixed-competitive manner, while cordycepin was not inhibitory. The adenosine deaminase inhibitor, 2-deoxy-coformycin produced a marked potentiation of the inhibitory effect of XA on Sam synthesis, but did not affect the inactivity of cordycepin. These results indicate that the inhibitory action of XA, but not cordycepin, on the methylation of nuclear RNA may be attributed to interference with the synthesis of SAM.
Cancer Lett 1979 Apr
PMID:Evidence that xylosyladenine affects methylation by inhibition of S-adenosyl-L-methionine synthesis. 31 36

A competitive radioimmunoassay for a saline-soluble human thymus-leukemia-associated antigen (HThy-L) was applied for quantitation of this antigen in leukemia and normal hematopoietic cell lines. Highly increased quantities of HThy-L were detected in all T-cell leukemia lines tested, regardless of the presence or absence of receptors for sheep erythrocytes. This elevated level of HThy-L in combination with high terminal deoxynucleotidyl transferase and adenosine deaminase activities and the presence of a T-lymphocyte-specific surface antigen appear to represent stable phenotypic characteristics of T-cell lines. Most normal B-cell lines had low quantities of HTy-L. The level of HThy-L was slightly elevated in a considerable number of lymphoma B-cell lines and in all non-T, non-B leukemia cell lines tested. No relationship existed between quantities of HThy-L and an expression of different surface immunoglobulin isotypes in B-cell lines. Low quantities of HThy-L were detected in leukemia myeloid and myeloma cell lines as well as in B-cell leukemia lines originating from patients with B-cells acute lymphoblastic leukemia. Apparently, the increased quantities of HThy-L in T-cell leukemia lines may be related to certain stages of T-cell differentiation at which leukemia cell transformation occurs.
J Natl Cancer Inst 1979 Sep
PMID:Quantitation of human thymus-leukemia-associated antigen in established hematopoietic cell lines by radioimmunoassay. 31 16


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