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

Deoxycytidine kinase, which phosphorylates deoxycytidine (CdR) and its analog, cytosine arabinoside (ara-C), has been purified 71-fold from human leukemic cells. Biochemical properties of the partially purified enzyme included a molecular weight of 68,000, Kms of 7.8 muM for CdR and 25.6 muM for ara-C, and optimal activity with ATP and GTP as phosphate donors. Ara-C phosphorylation was strongly inhibited by CdR (Ki = 0.17 muM) and dCTP (Ki = 7.3 muM) and was weakly inhibited by ara-CTP (Ki = 0.13 mM). Purification by calcium phosphate gel elution and DEAE chromatography effectively separated this enzyme from cytidine deaminase, which deaminates both CdR and ara-C, and from uridine-cytidine kinase, the enzyme which phosphorylates 5-azacytidine. CdR kinase activity was found to decrease and cytidine deaminase to increase with maturation of normal and leukemic granulocytes. Myeloblasts purified by Ficoll sedimentation revealed an average kinase activity of 15.4 U/mg protein in acute myelocytic leukemia and 12.3 U/mg protein in blastic crisis of chronic myelocytic leukemia (CML). The average ratio of CdR kinase to deaminase activity in crude cell extracts varied from 0.197 in AML and 0.089 in blastic crisis to 0.0004 in normal granulocytes, reflecting the changes which take place with cellular maturation. The absolute levels of kinase and deaminase and the ratio of these two enzymes varied considerably among patients with AML, indicating that quantitative differences may be found in the metabolism of CdR and its analogs in leukemic cells.
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PMID:Deoxycytidine kinase: properties of the enzyme from human leukemic granulocytes. 5 55

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

Deoxycytidine kinase (dCK) and deaminase (dCDA) are both key enzymes in the activation and inactivation, respectively, of several deoxycytidine antimetabolites. We determined the total dCK and dCDA activities using standard assays, in 28 human solid tumours grown as xenografts in nude mice, and four corresponding cell lines. dCK activities in colon tumours varied from 11 to 12 nmol/h/mg protein, in ovarian tumours from 3 to 10 nmol/h/mg protein, in soft tissue sarcomas from 2 to 7 nmol/h/mg protein and in squamous cell carcinomas of the head and neck about 45-fold, between 0.4 and 18 nmol/h/mg protein. The dCDA activities showed a larger variation, from 243 to 483, 14 to 1231, 3 to 7 and 1 to 222 nmol/h/mg protein, respectively. The ratios of dCK vs. dCDA activities in these tumours varied from 0.025 to 0.046, 0.004 to 0.240, 0.581 to 1.123 and from 0.012 to 4.227, respectively. In four cell lines (A2780, OVCAR-3, WiDr and UM-SCC-14C), sources for some of the above mentioned tumours, a different pattern in dCK and dCDA was observed than in the corresponding tumours. The variation in dCDA activities was in a smaller range (20-fold) than in the tumours (40-fold). In all cell lines dCK activity was higher than dCDA activity, in contrast to the corresponding tumours, in which the reverse pattern was observed. Previously, some of the tumours were tested for sensitivity to the deoxycytidine analogues 5-aza-deoxycytidine and 2',2'-difluorodeoxycytidine. In the sensitive tumours, both the highest and lowest dCK activity was observed, indicating that dCK activity in solid tumours is high enough to activate deoxycytidine analogues.
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PMID:Deoxycytidine kinase and deoxycytidine deaminase activities in human tumour xenografts. 829 52