| Stimulation by 6-azauridine of carbamoyl phosphate synthesis for pyrimidine biosynthesis in mouse spleen slices. | |
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MedLine Citation:
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PMID: 6185334 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. Slices of spleen from anaemic mice were incubated with [14C]bicarbonate in the presence and absence of 6-azauridine and the amounts of 14C that entered the de novo pyrimidine biosynthetic pathway were assessed and compared. Compounds analyzed included carbamoylaspartate, dihydroorotate, orotate plus its derivatives, acid-soluble uracil and cytosine 5'-nucleotides, nucleic acid pyrimidines, free pyrimidine bases and nucleosides. As the intracellular levels of carbamoyl phosphate and acid-soluble deoxyribonucleotides are known to be relatively low, the radioactivities of these compounds were not measured. Degradation of labelled uridine was limited in this tissues, therefore the radioactivity of degradative products of pyrimidines was not considered. 2. When the slices were incubated with 0.5 mM 6-azauridine for 10 min and then with [14C]bicarbonate for an additional 10 min and 30 min, the sum of radioactivity found in the above compounds, which represents the total amount of 14C that entered the pyrimidine pathway, was 2.1 and 2.3 times greater than when the tissue slices were incubated in the absence of the analogue. 3. When the 14C distribution among the carbon atoms of the molecules of labelled carbamoylaspartate and uracil was investigated, we found that more than 90% of the total 14C in these compounds derived directly from carbamoyl phosphate and the remaining portion was from aspartate, either in the presence or absence of 6-azauridine. 4. There was no indication that 6-azauridine altered [14C]bicarbonate permeation through the cell membrane or its intracellular metabolism. 5. These results, along with the pattern of early intermediate accumulation seen in the presence of 6-azauridine, indicate that 6-azauridine stimulates the production of carbamoyl phosphate for the pyrimidine biosynthetic pathway in the mouse spleen. 6. Of the radioactive early intermediates which accumulated, only orotate, its derivatives (orotidine and orotidine 5'-monophosphate) or both appeared in the medium, presumably the result of leakage through the cell membranes. 7. Stimulation of the pyrimidine pathway was not observed in the case of Ehrlich ascites tumour cells incubated under similar conditions with 6-azauridine. |
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Authors:
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M Tatibana; K Kita; T Asai |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: European journal of biochemistry / FEBS Volume: 128 ISSN: 0014-2956 ISO Abbreviation: Eur. J. Biochem. Publication Date: 1982 Nov |
Date Detail:
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Created Date: 1983-03-11 Completed Date: 1983-03-11 Revised Date: 2007-07-23 |
Medline Journal Info:
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Nlm Unique ID: 0107600 Medline TA: Eur J Biochem Country: GERMANY, WEST |
Other Details:
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Languages: eng Pagination: 625-9 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Azauridine / pharmacology* Bicarbonates / metabolism Carbamates / metabolism* Carbamyl Phosphate / metabolism* Carbon Radioisotopes / diagnostic use Kinetics Male Mice Mice, Inbred Strains Pyrimidines / biosynthesis* Spleen / drug effects, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Bicarbonates; 0/Carbamates; 0/Carbon Radioisotopes; 0/Pyrimidines; 54-25-1/Azauridine; 590-55-6/Carbamyl Phosphate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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