Uridine 5-phospho

This was phosphorylated with phosphorus oxychloride in pyridine, and the resulting 5-phospho-isopropylidene-uridine hydrolyzed to give 5-phospho-uridine, a substance whose phosphoryl group is hydrolyzed off at a lower rate than that of any other knowm ribose nucleotide. Hence uridylic acid is not 5-phospho-uridine. 

Figure 20.9 The positions in the pathway for de novo pyrimidine nucleotide synthesis where GLUCOSE provides the ribose molecule and GLUTAMINE provides nitrogen atoms. Glucose forms ribose 5-phosphate, via the pentose phosphate pathway (see chapter 6), which enters the pathway, after phosphorylation, as 5-phospho-ribosyl 1-pyrophosphate. Glutamine provides the nitrogen atom to synthesise carbamoylphos-phate (with formation of glutamate), and also to form cytidine triphosphate (CTP) from uridine triphosphate (UTP), catalysed by the enzyme CTP synthetase. It is the amide nitrogen of glutamine that is the nitrogen atom that is provided in these reactions.

Fig. lA. Anabolic and catabolic pathways of 5-FU. DPD dihydropyrimidine dehydrogenase, DP di-hydropyrimidinase, pUP beta-ureidopropionase, UP uridine phosphorylase, OPRT orotate phospho-ribosyl transferase, UK uridine kinase, TP thymidine phosphorylase, TK thymidine kinase, RNR ribonucleotide reductase. The three active metabolites (shown in rectangles) are FdUMP (5-fluoro-2 -deoxyuridine 5 -monophosphate) inhibiting TS (thymidylate synthase), and FUTP (5-fluorouridine 5 -triphosphate) and FdUTP (5-fluoro 2 -deoxyuridine 5 -triphosphate) interfering with RNA and DNA, respectively. 

Gulland and Jackson performed some experiments with 5-nucleotidase, a highly specific enzyme which dephosphorylates 5-phospho-adenosine and -inosine but not" 5-phospho-guanosine and -uridine it is apparently not yet known whether the enzyme dephosphorylates 5-phos-pho-cytidine. They found that a mixture of phosphodiesterase with 5-nucleotidase liberates 35% of the total phosphorus as inorganic phosphate, and therefore decided that two or more of the phosphoryl groups may be attached at position (5) of the ribose units. The 35% dephosphorylation, intermediate between 25 and 50%, was explained as the result of simultaneous, competitive diesterase action at A and B, on two or more phosphoryl groups ... 

A uridine pyrophosphate derivative of Ai -acetyl-n-glucosamine which contains an extra phosphate group has been isolated from a hot-water extract of hen oviducts. Uridine 5-phosphate and uridine 5-pyrophosphate have been recovered from acid hydrolyzates of this compound. A diphosphate ester of A-acetyl-n-glucosamine can also be obtained from acid hydrolyzates of this uridine compound. Because of the catalytic activity of phospho-A -acetyl-n-glucosamine mutase toward it, it is probably AT-ace-tyl-D-glucosamine 1,6-diphosphate. 

Four examples of structurally characterised, vanadate-inhibited phosphorylation enzymes working on the hydrolysis of phospho-ester bonds in nucleotides I, the vanadate-uridine complex of bovine pancreatic ribonuclease-A II, the vanadate complex of ribonuclease-Tj from the fungus Aspergillus oryzae-. III, the vanadate-uridine complex of cyclic nucleotide phosphodiesterase from the cruciferous plant Arabidopsis thaliana-, IV, human tyrosyl-DNA phosphodiesterase (Ur = uridine). 

Nucleotides are generally defined as phosphoric esters (of the carbohydrate moiety) of nucleosides. In polymerized forms (involving phospho-diester linkages), the nucleotides constitute the nucleic acids, which are fundamental components of all cells and viruses. Nucleotides also occur as mixed anhydrides, such as adenosine 5 -triphosphate and uridine 5 -(q -d-glucopyranosyl pyrophosphate), which comprise an important class of... 

The possibility that, during the alkaline hydrolysis of ribonucleic acid, tri-esters (18) - could be intermediates was ruled out on mechanistic groxmds."f > Furthermore, it was shown that the tri-ester, uridine 2 3 -(methyl phosphate) (18, R = CH3), synthesized by methylation of uridine 2 3 -cychc phosphate with diazomethane, is resistant to ribo-nuclease. f However, it has been observed that, when the benzyl ester of cytidylic acid 6 is partially hydrolyzed in acid, a significant proportion of the o isomer of this phosphoric diester is formed." ) In addition, the dinucleoside phosphates, such as adenylyl-(3 —>5 )-cytidine (14a), are also isomerized to the corresponding (2 - 5 )-dinucleoside phosphates by treatment with acid. " These studies suggest that cyclic triesters (or derivatives thereof) may be intermediates in isomerization of these phospho-diesters in acidic mediiun. 

Abbreviations used Gal-l-P, galactose-l-phosphate UDPG, uridine diphosphate glucose G-l-P, glucose-l-phosphate G-6-P, glucose-6-phosphate F-6-P, fructose-6-phosphate F-l,6-P, fructose-1,6-diphosphate G-3-P, glyceraldehyde-3-phosphate DHAP, dihydroxyacetone phosphate F-l-P, fructose-1-phosphate PG, 6-phospho-gluconic acid R-5-P, ribulose-5-phosphate S-7-P, sedoheptulose-7-phosphate. 

S ATP + deoxyadenosine <1-10> (<1> transfers a phospho group from specific nucleoside 5 -triphosphate donors to 5 -position of deoxyadenosine [1] <1> no activity with adenosine and guanosine [1] <2> no activity with cytidine, uridine, guanosine, deoxyguanosine and thymidine [3] <4> enzyme bears two separate but interacting active sites for deoxyadenosine and deoxycytidine kinase activity [5] <4> enzyme exists in two heterodimeric complexes, complex 1 deoxycytidine/deoxyadenosine kinase and complex II deoxyguanosine/deoxyadenosine kinase [6] <3> enzyme has both adenosine kinase and deoxyadenosine kinase activity [14]) (Reversibility <1-10> [1-9,11,12,15]) [1-9, 11, 12, 14, 15]... 

This was phosphorylated with phosphorus oxychloride in pyridine, and the resulting 5-phospho-isopropylidene-uridine hydrolyzed to give... 

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