scholarly journals De novo pyrimidine nucleotide biosynthesis in isolated rat glomeruli

1986 ◽  
Vol 30 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Pedro Cortes ◽  
Francis Dumler ◽  
Nathan W. Levin
Keyword(s):  
De Novo ◽  
Nucleotide Biosynthesis ◽  
Pyrimidine Nucleotide ◽  
Isolated Rat

scholarly journals Pyrimidine nucleotide metabolism in rat hepatocytes: evidence for compartmentation of nucleotide pools

1993 ◽  
Vol 293 (1) ◽  
pp. 207-213 ◽  
Author(s):  
W R Pels Rijcken ◽  
B Overdijk ◽  
D H van den Eijnden ◽  
W Ferwerda
Keyword(s):  
Orotic Acid ◽  
De Novo ◽  
Rat Hepatocytes ◽  
Nucleotide Metabolism ◽  
Double Labelling ◽  
Pyrimidine Nucleotides ◽  
Nucleotide Biosynthesis ◽  
Pyrimidine Nucleotide ◽  
Salvage Pathways ◽  
Lower Ratio

Pyrimidine nucleotide metabolism in rat hepatocytes was studied by measurement of the labelling kinetics of the various intermediates after double labelling with [14C]orotic acid and [3H]cytidine, the precursors for the de novo and the salvage pathways respectively. For the uridine nucleotides, differences were found for the 14C/3H ratios in the UDP-sugars, in UMP (of RNA) and in their precursor UTP, suggesting the existence of separated flows of the radioactive precursors through the de novo and the salvage pathways. Higher ratios in the UDP-sugars, which are synthesized in the cytoplasm, and a lower ratio in UMP (of RNA) relative to the 14C/3H ratio in UTP indicated that UTP derived from orotic acid is preferentially used for the cytoplasmic biosynthesis of the UDP-sugars. Uridine, derived from cytidine, is preferentially used for the nuclear-localized synthesis of RNA. In contrast to these findings, the 14C/3H ratios in the cytidine derivatives CMP-NeuAc and CMP (of RNA), and in the liponucleotides CDP-choline and CDP-ethanolamine, were all lower than that in the precursor CTP. This indicates a preferential utilization of the salvage-derived CTP for the synthesis of the liponucleotides as well as for RNA and CMP-NeuAc. Similar conclusions could be drawn from experiments in which the intracellular amounts of several uridine- and cytidine-nucleotide-containing derivatives were increased by preincubating the hepatocytes with unlabelled pyrimidine nucleotides or ethanolamine. Based on these data, we propose a refined model for the intracellular compartmentation of pyrimidine nucleotide biosynthesis in which three pools of UTP are distinguished: a pool of de novo-derived molecules and a pool of salvage-derived molecules, both of which are channelled to the site of utilization; in addition an ‘overflow’ pool exists, consisting of molecules having escaped from channelling. An overflow pool could also be distinguished for CTP, but no discrimination between de novo and salvage-derived molecules could be made.

scholarly journals The Effect of Reticulocytosis in the Rabbit on the Activities of Enzymes in Pyrimidine Biosynthesis

Blood ◽  
1962 ◽  
Vol 19 (5) ◽  
pp. 593-600 ◽  
Author(s):  
MYRON LOTZ ◽  
LLOYD H. SMITH
Keyword(s):  
De Novo ◽  
Pyrimidine Biosynthesis ◽  
Purine Nucleotide ◽  
Nucleotide Biosynthesis ◽  
Mature Erythrocyte ◽  
Pyrimidine Nucleotide

Abstract Five sequential enzymes leading to the formation of uridine-5'-phosphate were studied in acetophenylhydrazine-induced reticulocytes in the rabbit. All of these enzymes—aspartate carbamyltransferase, dihydroorotase, dihydroorotic dehydrogenase, orotidylic pyrophosphorylase, and orotidylic decarboxylase—decreased markedly in activity during in vivo maturation and aging of the reticulocytes. In analogy to previous studies on purine nucleotide biosynthesis, it is concluded that the reticulocyte, but not the mature erythrocyte, is capable of de novo pyrimidine nucleotide biosynthesis.

scholarly journals The influence of ammonia on purine and pyrimidine nucleotide biosynthesis in rat liver and brain in vitro

1978 ◽  
Vol 172 (3) ◽  
pp. 457-464 ◽  
Author(s):  
Stephen D. Skaper ◽  
William E. O'Brien ◽  
Irwin A. Schafer
Keyword(s):  
De Novo ◽  
Liver Homogenate ◽  
Purine Biosynthesis ◽  
Purine Nucleotide ◽  
Carbamoyl Phosphate ◽  
Phosphoribosyl Pyrophosphate ◽  
Nucleotide Synthesis ◽  
Nucleotide Biosynthesis ◽  
Pyrimidine Nucleotide

1. The effect of ammonia on purine and pyrimidine nucleotide biosynthesis was studied in rat liver and brain in vitro. The incorporation of NaH14CO3 into acid-soluble uridine nucleotide (UMP) in liver homogenates and minces was increased 2.5–4-fold on incubation with 10mm-NH4Cl plus N-acetyl-l-glutamate, but not with either compound alone. 2. The incorporation of NaH14CO3 into orotic acid was increased 3–4-fold in liver homogenate with NH4Cl plus acetylglutamate. 3. The 5-phosphoribosyl 1-pyrophosphate content of liver homogenate was decreased by 50% after incubation for 10min with 10mm-NH4Cl plus acetylglutamate. 4. Concomitant with this decrease in free phosphoribosyl pyrophosphate was a 40–50% decrease in the rates of purine nucleotide synthesis, both de novo and from the preformed base. 5. Subcellular fractionation of liver indicated that the effects of NH4Cl plus acetylglutamate on pyrimidine and purine biosynthesis required a mitochondrial fraction. This effect of NH4Cl plus acetylglutamate could be duplicated in a mitochondria-free liver fraction with carbamoyl phosphate. 6. A similar series of experiments carried out with rat brain demonstrated a significant, though considerably smaller, effect on UMP synthesis de novo and purine base reutilization. 7. These data indicate that excessive amounts of ammonia may interfere with purine nucleotide biosynthesis by stimulating production of carbamoyl phosphate through the mitochondrial synthetase, with the excess carbamoyl phosphate in turn increasing pyrimidine nucleotide synthesis de novo and diminishing the phosphoribosyl pyrophosphate available for purine biosynthesis.

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