Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-neoplastic activity of bacterial glutaminase on Ehrlich ascites tumor-bearing mice was studied by determining the reduction in the tumor cell count and extension of life span of the host after therapy. The therapeutic effect of glutaminase in relation to change in activity of glutaminolytic enzymes (glutamine amidohydrolase (GNase) and glutamine aminotransferase (GAt)) in liver and plasma were also studied. Bacterial glutaminase was shown to be effective in lowering the tumor burden with increased life span of the host. Glutamine amidohydrolase activity in the liver and plasma was raised significantly with increased tumor burden, whereas GAt activity remained unchanged. Following glutaminase therapy, this high level of GNase activity decreased in comparison to the untreated control. These changes were not seen when normal mice were treated with the same enzyme. Thus alteration in the enzyme levels, particularly GNase was observed to have some correlation with progression of the tumor growth.
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PMID:Investigation on glutamine amidohydrolase (EC 3.5.1.2) and glutamine aminotransferase (EC 2.5.1.15) activity in liver and plasma of EAC-bearing mice following glutaminase therapy. 145 Nov 3

Cytosine deaminase (CDase) catalyzes the conversion of cytosine to uracil and is also able to convert the clinically used antifungal agent 5-fluorocytosine (5FC) into the anticancer drug 5-fluorouracil (5FU). The enzyme was purified from bakers' yeast in a six-step procedure. Studies indicated that bakers' yeast CDase had a molecular weight of approximately 32 kDa and was composed of two subunits of equal molecular weights. Monoclonal antibodies were covalently attached to CDase, forming conjugates that could bind to antigens on tumor cell surfaces. The combination of L6-CDase and 5FC was equivalent in cytotoxic activity to 5FU when tested against the H2981 human lung adenocarcinoma cell line (L6 positive, 1F5 negative). 5FC alone was noncytotoxic. The activation of 5FC was immunologically specific since 1F5-CDase did not enhance 5FC activity.
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PMID:Generation of 5-fluorouracil from 5-fluorocytosine by monoclonal antibody-cytosine deaminase conjugates. 180 42

A new and simple enzymatic assay utilizing an acylpolyamine amidohydrolase and putrescine oxidase was adopted for measuring urinary polyamines (U-Pa). Serum carcinoembryonic antigen (S-CEA) was determined for comparison. The study population consisted of patients with pathologically proven nasopharyngeal carcinoma (NPC) who were referred to Kaohsiung Medical College Hospital. We found that polyamine levels were markedly elevated during radiotherapy but declined when the treatment was completed. Thus mean polyamines and the positive rate of polyamine elevation was higher in patients suffering from an active stage of the disease than in patients whose cancer had stabilized. However, the level of carcinoembryonic antigen was not elevated whilst undergoing radiotherapy. Therefore, routine measurement of polyamine levels may have a clinical utility in monitoring the disease state of the tumor. However, the low sensitivity of U-Pa test (22%) precludes its use as an effective screening method for this condition. Nevertheless, because of its simplicity, convenience and rapidity for monitoring NPC, U-Pa test should be considered a valuable tool in the clinical investigation of NPC patients.
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PMID:[Evaluation of urinary polyamines in patients with nasopharyngeal carcinoma]. 187 63

The two monoclonal antibodies (mAb), L6 (anti-carcinoma), and 1F5 [anti-(B-cell-lymphoma)], were chemically linked to the enzyme penicillin-V amidase (PVA), which hydrolyzes phenoxyacetamides, to explore the potential of using mAb-enzyme conjugates for the localization of chemotherapeutic drugs at tumor cells. The phenoxyacetamide derivatives of doxorubicin and melphalan were prepared, yielding the less toxic amides, doxorubicin-N-p-hydroxyphenoxyacetamide (DPO) and melphalan-N-p-hydroxyphenoxyacetamide (MelPO). These were hydrolyzed by PVA to doxorubicin and melphalan respectively. In vitro studies with the L6-positive lung carcinoma cell line, H2981, and the 1F5-positive B-cell lymphoma line, Daudi, showed that DPO was 80-fold less toxic to H2981 cells and 20-fold less toxic to Daudi cells than doxorubicin, and its toxicity was substantially increased when the H2981 cells were pretreated with L6-PVA or the Daudi cells were pretreated with 1F5-PVA. The cytotoxic effect was antigen-specific, since only the binding mAb-enzyme conjugate increased the cytotoxicity of the prodrug. MelPO was more than 1000-fold less toxic than melphalan to H2981 cells and more than 100-fold less toxic than melphalan to Daudi cells. Pretreatment with the mAb-PVA conjugates did not enhance the toxicity of MelPO in either cell line, because PVA hydrolyzes the phenoxyacetamide bond of MelPO too slowly to generate a toxic level of melphalan.
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PMID:Antibody-penicillin-V-amidase conjugates kill antigen-positive tumor cells when combined with doxorubicin phenoxyacetamide. 211 31

The activities of orotate phosphoribosyltransferase (OPRT), cytidine triphosphate (CTP) synthetase, deoxycytidine monophosphate (dCMP) deaminase, thymidine monophosphate (dTMP) kinase, uridine (Urd) kinase, thymidine (dThd) kinase, Urd and dThd phosphorylases, and DNA polymerase were examined in the eight human lung squamous cell carcinomas and five lung adenocarcinomas, and five tumor-adjacent normal lung tissues. All of these enzymes are involved in pyrimidine nucleotide synthesis. The metabolism of 5-fluorouracil (5-FU) was determined. The levels of these enzymes, except for OPRT, were high in tumor tissues and almost the same between lung squamous cell carcinomas and adenocarcinomas, with no statistical difference. The activities for phosphorylation and degradation of 5-FU were similar in each tissue type of tumor. As 5-FU is incorporated into tumor cells and is metabolized actively to 5-FU nucleotides in squamous cell carcinoma tissues, at almost the same level seen in adenocarcinoma tissues, this drug should have a wide clinical application.
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PMID:Comparison of pyrimidine nucleotide synthetic enzymes involved in 5-fluorouracil metabolism between human adenocarcinomas and squamous cell carcinomas. 216 41

The action of porphyrins, uroporphyrin I and III (URO I and URO III), pentacarboxylic porphyrin I (PENTA I), coproporphyrin I and III (COPRO I and COPRO III), protoporphyrin IX (PROTO IX) and mesoporphyrin (MESO), on the activity of human erythrocytes delta-aminolevulinic acid dehydratase, porphobilinogenase, deaminase and uroporphyrinogen decarboxylase in the dark and under UV light was investigated. Both photoinactivation and light-independent inactivation was found in all four enzymes using URO I as sensitizer. URO III had a similar action as URO I on porphobilinogenase and deaminase and PROTO IX exerted equal effect as URO I on delta-aminolevulinic acid dehydratase and uroporphyrinogen decarboxylase. Photodynamic efficiency of the porphyrins was dependent on their molecular structure. Selective photodecomposition of enzymes by URO I, greater specificity of tumor uptake by URO I and enhanced porphyrin synthesis by tumors from delta-aminolevulic acid, with predominant formation of URO I, underline the possibility of using URO I in detection of malignant cells and photodynamic therapy.
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PMID:Photodynamic and non-photodynamic action of several porphyrins on the activity of some heme-enzymes. 231 33

1-beta-D-Arabinofuranosyl-5-azacytosine (ara-5-aza-Cyd) had potent cytotoxicity against human T-type lymphoblastic cells in culture. When Molt-4 cells were exposed to ara-5-aza-Cyd for 24 h, clonogenic survival was reduced by 50 and 98% at initial concentrations of 10(-7) and 10(-6) M, respectively, compared to 3 X 10(-8) and 10(-6) M, respectively, for the same effect with 1-beta-D-arabinofuranosylcytosine (ara-C). The analogue is chemically unstable, with a t1/2 of 12 h at 37 degrees C in phosphate-buffered saline. ara-5-aza-Cyd is not significantly deaminated by human Cyd-deoxycytidine (dCyd) deaminase, in contrast to ara-C. It is phosphorylated by human cytoplasmic dCyd kinase, with a Km of 55 microM and a relative Vmax of 310% compared to dCyd. The primary metabolite (70%) in Molt-4 cells was identified as ara-5-aza-Cyd triphosphate. Thymidine but not uridine or amino acid incorporation was inhibited by ara-5-aza-Cyd. ara-5-aza-Cyd was incorporated in a dose-dependent manner into DNA, but not RNA, primarily in internucleotide linkage as the original compound. Incorporation into the cellular methanol-insoluble fraction was 3- to 5-fold higher at 8 h than was ara-C incorporation. ara-5-aza-Cyd may have a unique activity against tumor cells resistant to ara-C, particularly where high Cyd-dCyd deaminase activity is a factor. The mode of action, like that of ara-C, is probably mediated through its incorporation into DNA and inhibition of DNA synthesis.
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PMID:Metabolism of 1-beta-D-arabinofuranosyl-5-azacytosine and incorporation into DNA of human T-lymphoblastic cells (Molt-4). 241 96

We have studied the differential susceptibility to N-glycanase (peptide-N4-[N-acetyl-beta-glucosaminyl]asparagine amidase) of oligosaccharides at the individual glycosylation sites of mouse TSH and free alpha-subunits. Mouse thyrotropic tumor tissue or hypothyroid pituitary tissue were incubated with D-[2-3H]mannose for 6 h. [3H]Mannose-labeled TSH or free alpha-subunits were obtained from homogenates using specific antisera and were digested with N-glycanase in their native state or after heat denaturation and reduction in the absence or presence of detergents. Tryptic fragments of the digestion products were then analyzed by reverse phase HPLC so that the effects of N-glycanase at the individual glycosylation sites could be determined. N-Glycanase treatment of native molecules did not cleave oligosaccharides efficiently at Asn56 of alpha-subunits and Asn23 of TSH beta, whereas oligosaccharides at Asn82 of alpha-subunits were more susceptible regardless of whether the alpha-subunits were combined with TSH beta. Heat denaturation, reduction, and the presence of detergents did not substantially increase the cleavage by N-glycanase of the protected oligosaccharides, suggesting that the primary structures of the TSH subunits influenced efficiency at specific sites. Pretreatment of free alpha-subunits with trypsin failed to enable N-glycanase to work fully, as oligosaccharides at Asn56 were cleaved less effectively than those at Asn82. Thus, the susceptibility to N-glycanase differs at the individual glycosylation sites of mouse TSH and free alpha-subunits, and these differences may result from effects of the primary structures of the TSH subunits.
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PMID:Differential susceptibility to N-glycanase at the individual glycosylation sites of mouse thyrotropin and free alpha-subunits. 245 9

The activities of aspartate transcarbamylase (de novo pyrimidine biosynthesis pathway) and of deoxycytidine kinase as well as deoxycytidine deaminase (salvage pyrimidine biosynthesis pathway) were determined in extracts prepared from 40 brain tumors of different types in comparison with extracts from normal nervous tissues. Aspartate transcarbamylase, which is undetectable in normal brain tissue, is present in all tumor samples and in some cases rises to very high activities. Deoxycytidine kinase activity is present in all tissues but its level is generally higher in tumors. Deoxycytidine deaminase is present in all the tissues which were analyzed, although its activity is lower in some of the tumor samples. 1-beta-D-Arabinofuranosylcytosine is a substrate for both deoxycytidine kinase and deaminase in all the samples used except one. These results suggest some potential for the utilization of 1-beta-D-arabinofuranosylcytosine and N-(phosphonacetyl)-L-aspartate in the treatment of brain tumors.
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PMID:Pyrimidine pathways enzymes in human tumors of brain and associated tissues: potentialities for the therapeutic use of N-(phosphonacetyl-L-aspartate and 1-beta-D-arabinofuranosylcytosine. 282 6

N-Carbamoyl-beta-alanine (NC beta A) amidohydrolase (EC 3.5.1.6) is regulated in opposing fashion by the substrate, NC beta A and the product, beta-alanine. The native enzyme from rat liver has a molecular weight of 235,000 in the absence of ligands. NC beta A and substrate analogs (N-amidino-beta-alanine, N-carbamoyl-glycine) produced association of the enzyme. beta-Alanine and its analog gamma-aminobutyrate caused dissociation of the enzyme and produced inhibition. Negative cooperativity was observed for the binding of all ligands as measured by the change in polymerization of the enzyme, with an average Hill coefficient (napp) of 0.5. Enzyme that had been dissociated by preincubation with beta-alanine had little or no initial activity; only after a lag of 9 s was a steady state progress curve evident. The existence of a regulatory site is proposed as a model to explain physical and kinetic data. The enzyme activity was highest in rat liver and detectable in kidney; activity was not detected in brain, lung, muscle, or spleen of rat, nor in mouse Ehrlich ascites tumor cells. The rat liver enzyme has a pH optimum of 6.8, with a Km of 6.5 microM for NC beta A and a Ki of 1.08 mM for beta-alanine at this pH.
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PMID:Regulation of N-carbamoyl-beta-alanine amidohydrolase, the terminal enzyme in pyrimidine catabolism, by ligand-induced change in polymerization. 310 50


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