Uracil anabolism

In summary, a catabolic function for uridine phosphorylase is clear. However, this enzyme may also participate in the anabolism of uracil, which is the evident function of uracil phosphoribosyltransferase. The operation of these apparently alternative routes of uracil anabolism in living cells has not yet been evaluated. 

Effect of Concentration on the Relative Amount op Uracil Anabolized and Catabolized IN Rat Liver Slices ... 

The recent availability of oral formulations of 5-FU involving the ability to modulate the anabolic and catabolic metabolism of 5-FU with LV and dihydropyrimidine dehydrogenase (DPD) inhibitors has provided a substantial improvement in the ease of administration and may probably improve the efficacy of fluoropyrimidine-induced radiosensitization. Such oral fluoropyrimidines include UFT (uracil tegafur) plus oral LV (Orzel ), an oral DPD-inhibitory fluoropyrimidine (DIF), and capecitabine (Xeloda Roche). 

The extraction of some anabolic steroids directly from bovine tissue was reported by Huopalahti and Henion (108). SFE was performed with CO2 at 60 °C and 405 bar and anlytes were collected in precooled methanol. The quantitation of the analytes was carried out with HPLC-atmospheric pres-sure-ClMS. The detection limit was 100 pg/mL. Bovine muscle tissue was also used for the determination of residues of 2-thiouracil, 6-methil-2-thio-uracil, 6-propyl-2-thiouracil, and 6-phenyl-2-thiouracil by GC-MS (109). The analytes, extracted with acetonitrile from homogenized beef muscle, were spiked with a surrogate compound, 5-ethyl-2-thiouracil, transferred to a column and methylated. The products were extracted with acetonitrile or supercritical CO2. 2,4,5-Triclorophenoxyacetate was used as the internal standard. 

A great many fraudulent bases related to cytosine and its nucleosides have been synthesised, either with the chemotherapeutic object of inhibiting one or more enzymatically controlled anabolic processes involved in nucleic acid syntheses, or of attempting incorporation into the DNA or RNA, with the object of producing mutations of the normal replication. Chemical reactions have also been carried out on the intact nucleic acids, for this purpose. Among the latter, one which is highly specific to cytosine is the reaction with hydroxylamine. This apparently adds first across the 5,6-double bond, followed by conversion of the 4-amino group to —NffOH, elimination of the first hydroxylamine, and hydrolysis to uracil [280, 281]. The G-C pair is... 

The catabolism of uridine and cytidine by this route has value to the cell in that the ribose 1-phosphate produced may be degraded in energy-yielding reactions of the glycolytic pathway (see Chapter 6). Because of the ready reversibility of uridine phosphorolysis, this enzyme may contribute to the anabolism of uracil. 

The reversibility of uridine phosphorolysis suggests that uridine phosphorylase activity of the cell may be able to operate in the direction of synthesis, utilizing endogenous ribose 1-phosphate, and thereby contribute to the anabolism of uracil. Thus, uridine phosphorylase and uridine kinase acting in sequence would elevate uracil to the nucleotide level. 

However, for adenine, guanine, and uracil, the dominant route of anabolism is by way of their ribonucleotide derivatives and traffic along the deoxyribosidic route is not ordinarily significant. Because cytosine is not a substrate for nucleoside phosphorylases, incorporation by the phos-phorylase-kinase route is not possible for this base. The other pyrimidine base of DNA, thymine, is poorly anabolized by both animal and bacterial cells, in spite of the fact that most cells possess thymidine phosphorylase, the action of which is readily reversible. This suggests that ordinarily cellular supplies of deoxyribose 1-phosphate are not available for base anabolism. Experiments are cited below in which it was demonstrated that a significant contribution to the biogenesis of deoxyribose of DNA in E. colt cells did not occur by a route other than ribonucleotide reduction. 

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