Ribonucleosides monophosphates

A method for the synthesis of pApUp that uses the triester method has appeared,324 and the concept of phosphorylating preformed oligonucleotides has been extended to the synthesis of 5 -phosphates of di(ribonucleoside) monophosphates by way of phosphoric triester intermediates 325 The terminal 3 -hydroxyl group was protected with the... 

Walseth et al. (W3) separated 5 -ribonucleoside monophosphates using ion-pair chromatography. The chromatognq>hic system has been used to analyze tissue nucleotides, to purify nucleoside monophosphates and cyclic nucleotides, and to monitor enzymatic reactions involving cyclic nucleotide phosphodiesterase, 5 -nucleotidase, and adenylate cyclase. 

RNA (RiboNucleic Acid), like DNA, is a form of nucleic acid found in cells. RNA, like DNA, is a polymer composed of nucleoside monophosphates. The nucleoside monophosphates in RNA are called ribonucleoside monophosphates, however, because they contain the sugar ribose instead of 2-deoxyribose, as is found in DNA. 

Purine salvage usually involves phosphoribosyltransferase reactions, which generate ribonucleoside monophosphates (rNMPs) from the purine bases and 5-phosphoribosyl-l-pyrophosphate (PRPP). These are phosphorylated to diphosphates (rNDPs) and then reduced to deoxyribonucleotides (dNDPs) with ribonucleotide reductase. 

The 3 -hydroxyl terminus of the growing RNA chain makes a nucleophilic attack on the a-phosphate (the innermost phosphate) of the ribonucleoside triphosphate that has been selected by base pairing to the template strand of the duplex DNA. RNA polymerase catalyzes the reaction. A ribonucleoside monophosphate residue is added to the chain as a result, and the chain has grown in the 5 —> 3 direction that is, the chain has grown at its 3 end. As "with all Watson-Crick base pairing, the strands are antiparallel that is, the RNA chain is assembled in the 3 —> 5 direction with respect to the polarity of the template strand of the DNA. 

Zeatin is found in com and other plants as the free base, 6-(4-hydroxy-3-methyl-frans-2-butenylamino)purine, as well as in the form of the ribo-nucleoside and the ribonucleoside 5 -phosphate. 6-Benzylaminopurine can also be converted to its ribonucleoside and ribonucleoside monophosphate by plant enzymes. Mevalonate is presumed to be a precursor of the natural cytokinins, and cysteine and methionine are thought to be precursors of the thio and methyl portions of the 2-methylthio cytokinin derivatives. 

Another instance of the induction of enzymes not ordinarily present in E. coli which occurs upon infection with bacteriophage T2 (see Section I, D and II, E) is found in the work of Bello and Bessman ( 4), who isolated from T2-infected E. coli, a deoxynucleoside monophosphate kinase with specificities quite distinct from those of the kinases discussed above. The phage-induced kinase is specific for deoxj/ribonucleoside monophosphates and will phosphorylate three of the four nucleotides destined for phage DNA deoxyguanylate, thymidylate, and hydroxymethyldeoxycyti-dylate. The enzyme does not phosphorylate deoxyadenylate. 

In most cases the traditional abbreviations based on the term nucleoside monophosphate are used. Thus AMP stands for adenosine monophosphates (adenylate), UMP for uridine monophosphate (midylate), and NMP for any ribonucleoside monophosphate. Similarly, dAMP stands for deoxyadenosine monophosphate (deoxyadenylate), dUMP for deoxyuridine monophosphate (deoxyuridylate), and dNMP for any deoxyribonucleoside monophosphate. To illustrate certain points, the base, sugar, and phosphate group are indicated individually AMP = ARP dUMP = UdRP etc. 

The principal feature which distinguishes the metabolism of allopurinol in leishmania is the rapid formation of allopurinol ribonucleoside monophosphate (HPPR-MP). This can be demonstrated by grow hjL donovani in the presence of (6- C)-allopurinol and analyzing the perchloric acid-soluble extracts by high performance liquid chromatography (HPLC). It is the predominant radioactive material in the elution profile. The chromatogram reveals three other radio-labeled compounds. The first radioactive metabolite, which appears ahead of HPPR-MP, is 4-aminopyrazolopyrimidine ribonucleoside monophosphate (APPR-MP). The second is between ADP and GDP and the third between ATP and GTP. These are 4-aminopyrazolopyrimidine ribonucleoside diphosphate (APPR-DP) and triphosphate (APPR-TP), respectively. When the RNA from these cells is analyzed, 4-aminopyrazolopyrimidine (APP) can be found in the RNA. ... 

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

The above complexes have been shown to mimic the second step of RNA hydrolysis as well, i.e. the-efficient cleavage of ribonucleoside 2, 3 -cyclic monophosphates [55] with bell-shaped pH-rate profile. With these substrates 37 showed much higher bimetallic cooperativity the dime/2 m0nomer ratios range between 64 and 457 for the different 2, 3 -NMPs used, while for 38 this ratio varies between 1 and 26. Since the mononuclear complexes have nearly the same activity toward the different 2, 3 -NMPs, these kinetic data indicate a notable base-selectivity of the dimer complexes. Since no correlation was observed with the size,... 

Base Ribonucleoside/ deoxyribonucleoside Ribonucleotide/ deoxyribonucleotide (5 -monophosphate)... 

Z. and Liu, S.J. (1997) Rapid and highly selective cleavage of ribonucleoside 2, 3 -cyclic monophosphates by dinuclear Cull complexes. Angew. Chem., Int. Ed., 36, 2678-2680,... 

Figure 8-4 gives the structures and names of the four major deoxyribonucleotides (deoxyribonucleo-side 5 -monophosphates), the structural units of DNAs, and the four major ribonucleotides (ribonucleoside 5 -monophosphates), the structural units of RNAs. Specific... 

Ribonucleoside 2, 3 -cyclic monophosphates are isolatable intermediates, and ribonucleoside 3 -monophosphates are end products of the hydrolysis of RNA by certain ribonucleases. Other variations are adenosine 3, 5 -cyclic monophosphate (cAMP) and guanosine 3, 5 -cyclic monophosphate (cGMP), considered at the end of this chapter. 

Shaw (115) reported a 300-fold purification of enzyme from tobacco leaves. Activity of the enzyme was optimal at pH 5.5-5.7, and divalent cations were not required for activity. The enzyme possessed high activity toward ribonucleoside 2 - and 5 -monophosphates and glucose 1-phosphate. There was no activity toward RNA or phosphodiesters. Fluoride acts as a noncompetitive inhibitor for this enzyme. This behavior of fluoride is in contrast to the behavior with prostatic acid phosphatase where the inhibition is strictly competitive. 

Absorption spectra of the common ribonucleoside-5 -monophosphates giving the maximum absorbance are as follows AMP, 15.4 x 103 ... 

In the 1960s, Schwartz described the phosphorylation of adenosine with trimetaphosphate to yield 2 - and 3 -AMP. The strong alkaline conditions used for this transformation were not likely to occur on the primitive Earth [137]. Similarly, all natural ribonucleosides were phosphory-lated to corresponding 2 - and 3 -nucleotide monophosphates with sodium trimetaphosphate at high pH and temperature [138,139]. When the reaction was performed under similar experimental conditions at lower pH, 2/,3/-cyclic phosphate nucleotides were recovered as the major products [140]. Magnesium ion catalyzes this transformation in neutral water solution [141]. 

Ribonucleoside 5 -monophosphates Adenosine 5 -phosphoric acid Guanosine S -phosphoric acid Cytidine 5 -phosphoric acid Uridine 5 -phosphoric acid... 

Nucleoside diphosphates and triphosphates are interconverted by nucleoside diphosphate kinase, an enzyme that has broad specificity, in contrast with the monophosphate kinases. X and Y can represent any of several ribonucleosides or even deoxyribonucleosides. 

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