Disease relevance of DCTD

• Primary structure of human deoxycytidylate deaminase and overexpression of its functional protein in Escherichia coli [1].
• Deoxycytidylate deaminase isolated from normal human lymphocytes and from mononuclear leucocytes from patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia and acute monocytic leukemia has been characterized in regard to the substrate, dAMP and the allosteric regulators dCTP and dTTP [2].
• T4-phage deoxycytidylate deaminase is a metalloprotein containing two zinc atoms per subunit [3].
• Assessment of the effect of phosphorylated metabolites of anti-human immunodeficiency virus and anti-hepatitis B virus pyrimidine analogs on the behavior of human deoxycytidylate deaminase [4].
• Human cytomegalovirus requires cellular deoxycytidylate deaminase for replication in quiescent cells [5].

High impact information on DCTD

• Activities of deoxycytidine kinase, deoxycytidylate deaminase, and pyrimidine nucleoside monophosphate kinase were not different between any of the leukemic cell types [6].
• A tale of two enzymes, deoxycytidylate deaminase and thymidylate synthase [7].
• Regulation of pyrimidine deoxyribonucleotide metabolism by substrate cycles in dCMP deaminase-deficient V79 hamster cells [8].
• A mutant V79 hamster fibroblast cell line lacking the enzyme dCMP deaminase was used to study the regulation of deoxynucleoside triphosphate pools by substrate cycles between pyrimidine deoxyribosides and their 5'-phosphates [8].
• In addition, dFdCTP inhibited partially purified dCMP deaminase with a 50% inhibitory concentration of 0.46 mM [9].

Chemical compound and disease context of DCTD

• A T4-phage deoxycytidylate deaminase mutant that no longer requires deoxycytidine 5'-triphosphate for activation [10].
• Elevations of plasma urate and serum dCMP deaminase are therefore both early features of pre-eclampsia [11].
• The activity of serum deoxycytidylate deaminase, not hitherto reported to increase after myocardial infarction, has been investigated and the results have been related to other cardiac enzymes, including the MB fraction of creatine phosphokinase [12].
• The diagnostic value of deoxycytidylate deaminase (dCMP) in the diagnosis of acute myocardial infarction (AMI) was examined in 31 healthy controls and 32 patients with proven AMI [13].
• Deoxycytidine appears to protect from deoxyguanosine toxicity by metabolism to thymidylate via a dCMP deaminase pathway, thus replenishing the thymidylate pools which have been depleted by deoxyguanosine [14].

Biological context of DCTD

• We set out to study the pharmacogenomics of CDA and DCTD [15].
• There were 29 SNPs in DCTD, including one nonsynonymous cSNP, 172 A>G (Asn58Asp), in Caucasian American DNA [15].
• The sequence of several cyanogen bromide-cleaved peptides derived from HeLa cell dCMP deaminase are all contained within the deduced amino acid sequence [1].
• A DNA fragment encompassing the gene for deoxycytidylate deaminase has been isolated from a human lung fibroblast genomic library and sequenced in both directions through 26,764 base pairs [16].
• We conclude that dFdC-induced inhibition of dCMP deaminase resulted in a decrease of dFdCTP catabolism, contributing to the concentration-dependent elimination kinetics [9].

Anatomical context of DCTD

• Deoxycytidylate deaminase activity in non-stimulated and phytohemagglutinin-stimulated human lymphocytes, and in leukemic cells [2].
• CHO cells, which intrinsically lack both cytidine deaminase (CD) and deoxycytidylate deaminase (dCMPD), are sensitized to X ray by 5-chlorodeoxyuridine (CldU) but display no significant sensitization with CldC + H4U [17].
• We evaluated the effects of cell cycle phase and cell differentiation on the activity of cytidine deaminase, deoxycytidylate deaminase and deoxycytidine kinase in myeloid cell lines [18].

Associations of DCTD with chemical compounds

• Recombinant Asp58 DCTD had 11 +/- 1.4% of WT activity for gemcitabine monophosphate with a significantly elevated level of immunoreactive protein [15].
• Polyacrylamide gel electrophoresis revealed a prominent protein band which comigrated with affinity purified HeLa dCMP deaminase, while Western blot analysis yielded an immunoreactive band which comigrated with the single immunoreactive affinity column purified dCMP deaminase band [1].
• Accumulation of 1-beta-D-arabinofuranosyluracil 5'-monophosphate was inversely related to the half-life of araCTP retention and directly related to dCMP deaminase activity in cell free extracts [19].
• Cytidine and deoxycytidylate deaminase inhibitors increased the extent of (FdCyd) DNA synthesis, but they had little if any effect on formation of (FUra) RNA [20].
• Deoxycytidylate deaminase, catalyzing the conversion of dCMP to dUMP, is an important enzyme in the de novo synthesis of thymidine nucleotides [4].

Other interactions of DCTD

• Here, we have demonstrated that HCMV increases expression of the cellular deoxycytidylate deaminase (dCMP deaminase), which provides the substrate for TS by converting dCMP to dUMP [5].
• We observed an increase in dCMP deaminase protein levels, whereas deoxyuridine triphosphatase (dUTPase), another cellular enzyme that may provide dUMP by hydrolysing dUTP, was undetectable [5].
• Effect of 5-fluoro-2'-deoxyuridine and hydroxyurea on the phytohemagglutinin-induced increase of thymidine kinase, replicative DNA polymerase, deoxycytidylate deaminase and CDP reductase activities in human lymphocytes [21].

Analytical, diagnostic and therapeutic context of DCTD

• The binding characteristics of T2 phage induced deoxycytidylate deaminase were examined through the use of ultrafiltration and equilibrium dialysis [22].
• 5-mdCMP deaminase co-purifies on SDS-PAGE with dCMP deaminase and has an apparent molecular weight of 25 kDa [23].
• Plasma urate and serum deoxycytidylate deaminase measurements for the early diagnosis of pre-eclampsia [11].

References