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)

Regulation of the levels of aspartate transcarbamylase (carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2) and dihydroorotase (L-5,6-dihydro-orotate amidohydrolase, EC 3.5.2.3) was studied in synchronous cultures of the eucaryotic microorganism Chlorella. Analytical polyacrylamide gel electrophoresis and sucrose density-gradient centrifugation studies revealed that these cells contain a single aspartate transcarbamylase and a dihydroorotase with apparent molecular weights of 160 000 and 80 000, respectively. In synchronous cells cultured in nitrate medium, these two enzymes accumulated in single step-patterns over different periods of the cell cycle. In contrast, these enzymes accumulated in a coordinate manner throughout the cell cycle in ammonium medium. Experiments with inhibitors of protein and RNA synthesis indicated that dihydroorotase is stable in vivo and suggested that cell cycle changes in the turnover rate of aspartate transcarbamylase might determine whether or not these enzymes accumulate in a coordinate manner. Although uracil and uridine could be absorbed and metabolized by the cells, synthesis of these two enzymes could not be repressed by culturing synchronous cells in medium, containing high concentrations (29-40 mM) of uracil or uridine, for an entire cell cycle.
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PMID:Coordinate and non-coordinate accululation of aspartate transcarbamylase and dihydroorotase in synchronous Chlorella cells growing on different nitrogen sources. 2 96

A combined genetic, biochemical, and immunological approach has clarified structural relationships involving the first three enzymes of de novo pyrimidine biosynthesis. A procedure involving antibody and protein A-Sepharose was used to isolate the enzymes carbamoyl-phosphate synthase [ATP:carbamate phosphotransferase (dephosphorylating, amido-transferring), EC 2.7.2.9], aspartate transcarbamoyltransferase (carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2), and dihydro-orotase (L-5,6-dihydroorotate amidohydrolase, EC 3.5.2.3) from Chinese hamster ovary cell CHO-K1, the uridine-requiring auxotroph Urd(-)A, and selected Urd(-)A revertants. The enzymes of Urd(-)A and the Urd(-)A revertants were significantly altered in activity, native structure, and molecular weight from those of CHO-K1. The results presented permit the conclusion that (i) these three enzymes reside in a single multifunctional 220,000-dalton polypeptide; (ii) the aspartate transcarbamoyltransferase activity is located on a portion ( approximately 20,000 daltons) at one end of the polypeptide; (iii) this portion may also be required for monomers to aggregate into the multimeric from present in mammalian cells; (iv) the mutations in Urd(-)A and the Urd(-)A revertants lie in the structural gene for this multifunctional protein; and (v) increased sensitivity to proteases could account for the alterations in the structure of these enzymes in the mutants.
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PMID:Alteration in structure of multifunctional protein from Chinese hamster ovary cells defective in pyrimidine biosynthesis. 3 10

Glutamine-dependent carbanoyl phosphate synthase [ATP6carbamate phosphotransgerase (dephosphorylating), EC 2.7.2.9], aspartate transcarbamoylase (carbamoylphosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) and dihydroorotase (L-5,6-dihydroorotate amidohydrolase, EC 3.5.2.3), are copurified as a high-molicular-weight complex from extracts of unfertilized eggs of Rana catesbeiana. UTP is required to maintain the integrity of the complex during the last two purification steps. Removal of the nucleotide results in dissociation of the complex. Based on sedimentation behavior in glycerol gradients, the dissociated carbamoyl phosphate synthase has an apparent molecular weight of 260,000 +/- 20,000 and that of dihydroorotase is estimated at 280,000 +/- 20,000. Aspartate transcarbamoylase is broadly distributed over the gradient. The addition of ATP, 5-phosphoribosyl-1-pyrophosphate, Mg++, or inorganic phosphate to the dossociated complex results in the appearance of a peak of aspartate transcarbamoylase activity with an apparent molecular weight of 110,000 +/- 10,000. Icubation of a mixture of the dissociated enzymes with UTP and Mg++ leads to their reassociation into the high-molecular-weight complex.
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PMID:Reversible dissociation of a carbamoyl phosphate synthase-aspartate transcarbamoylase-dihydroorotase complex from ovarian eggs of Rana catesbeiana: effect of uridine triphosphate and other modifiers. 16 71

Mammalian DHOase (S-dihydroorotate amidohydrolase, EC 3.5.2.3) is part of a large multifunctional protein called CAD, which also has a carbamoyl-phosphate synthetase [carbon-dioxide: L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating), EC 6.3.5.5] and aspartate transcarbamoylase (carbamoyl-phosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) activities. We sequenced selected restriction fragments of a Syrian hamster CAD cDNA. The deduced amino acid sequence agreed with the sequence of tryptic peptides and the amino acid composition of the DHOase domain isolated by controlled proteolysis of CAD. Escherichia coli transformed with a recombinant plasmid containing the cDNA segment 5' to the aspartate transcarbamoylase coding region expressed a polypeptide recognized by DHOase domain-specific antibodies. Thus, the order of domains within the polypeptide is NH2-carbamoyl-phosphate synthetase-DHO-aspartate transcarbamoylase-COOH. The 334-residue DHOase domain has a molecular weight of 36,733 and a pI of 6.1. A fragment of CAD having DHOase activity that was isolated after trypsin digestion has extensions on both the NH2 (18 residues) and COOH (47-65 residues) termini of this core domain. Three of five conserved histidines are within short, highly conserved regions that may participate in zinc binding. Phylogenetic analysis clustered the monofunctional and fused DHOases separately. Although these families may have arisen by convergent evolution, we favor a model involving DHOase gene duplication and insertion into an ancestral bifunctional locus.
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PMID:Mammalian dihydroorotase: nucleotide sequence, peptide sequences, and evolution of the dihydroorotase domain of the multifunctional protein CAD. 196 94

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

The induction of 2-amino-Delta(2)-thiazoline-4-carboxylic acid hydrolase (ATCase) and N-carbamoylcysteine amidohydrolase (NCCase), both of which are involved in the conversion step of 2-amino-Delta(2)-thiazoline carboxylic acid (ATC) to cysteine, was studied with Pseudomonas putida AJ3865. We found that L-ATC induced L-ATCase and L-NCCase, but that D-ATC induced only L-NCCase, whereas L- or D-NCC and thiazoline derivatives did not induce both enzymes. The bacterium showed neither D-ATCase nor D-NCCase activities, indicating that the role of L-ATC and D-ATC was different in the enzyme induction. We also found new inducers, d- and l-methionine, S-methyl-L-cysteine, cysteic acid, and 2-aminoethane sulfonic acid. However, the induction level of both enzymes by new inducers was much lower than those by L-ATC and D-ATC. Furthermore, the induction rate of both enzymes was synergistically increased only under a combination of D,L-ATC and new inducers. S-Compounds, however, such as new inducers except S-methyl-L-cysteine, inhibited both enzyme activities. This is the first report on the new inducers, synergistic induction, and the new inhibitors of L-ATCase and L-NCCase.
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PMID:Induction of 2-amino-D2-thiazoline-4-carboxylic acid hydrolase and N-carbamoyl-l-cysteine amidohydrolase by S-compounds in Pseudomonas putida AJ3865. 1248 19