Nucleoside diphosphates nucleotides

Other nucleoside diphosphate sugar compounds are known, eg, UDPGal. In addition, the same sugar may be linked to different nucleotides. For example, glucose may be linked to uridine (as shown above) as well as to guanosine, thymidine, adenosine, or cy-tidine nucleotides. 

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). 

UDP and UTP are selective agonists of certain of the P2Y receptors. It is not yet clear what factors control the release of uridine nucleotides into the extracellular space. UTP can be formed from UDP in the extracellular space by the action of the enzyme nucleoside diphosphokinase, which catalyzes the transfer of the -phosphate of nucleoside triphosphates to nucleoside diphosphates, e.g., ATP + UDP —> ADP + UTP. 

The Fe-protein has the protein fold and nucleotide-binding domain of the G-protein family of nucleotide-dependent switch proteins, which are able to change their conformation dependent on whether a nucleoside diphosphate (such as GDP or ADP) is bound instead of the corresponding triphosphate (GTP or ATP). However, nucleotide analogues, which induce the conformational switch of the Fe-protein, do not allow substrate reduction by the MoFe-protein, nor does reduction of the MoFe-protein by other electron-transfer reagents (whether small proteins or redox dyes) drive substrate reduction. Only the Fe-protein can reduce the MoFe-protein to a level that allows it to reduce substrates such as... 

DNA and RNA synthesis De novo formation of purine and pyrimidine nucleotide Nucleoside diphosphate reductase Thymidylate synthase Polymerase reactions Chapter 20... 

The synthesis of purine nucleotides (1) starts from IMP. The base it contains, hypoxanthine, is converted in two steps each into adenine or guanine. The nucleoside monophosphates AMP and CMP that are formed are then phos-phorylated by nucleoside phosphate kinases to yield the diphosphates ADP and GDP, and these are finally phosphorylated into the triphosphates ATP and CTP. The nucleoside triphosphates serve as components for RNA, or function as coenzymes (see p. 106). Conversion of the ribonucleotides into deoxyribo-nucleotides occurs at the level of the diphosphates and is catalyzed by nucleoside diphosphate reductase (B). 

This enzyme [EC 3.6.1.6] catalyzes the hydrolysis of a nucleoside diphosphate to produce a nucleotide (that is, a nucleoside monophosphate) and orthophosphate. NDP substrates include IDP, GDP, UDP, as well as d-ribose 5-diphosphate. 

The important role of glyeosyl esters of nucleoside pyrophosphates (often referred to loosely as sugar nucleotides or nucleoside diphosphate sugars ) in carbohydrate metabolism is well known. Two comprehensive Chapters of this Series,1,2 as well as several surveys in other publications3-5 have already appeared. These reviews deal mainly with the metabolism of these compounds, and... 

S Additional information <5, 7, 11, 25> (<5,7,11 > in the absence of nucleoside diphosphates the enzyme undergoes Mg -dependent stoichiometric autophosphorylation using ATP, GTP or y-thiotriphosphate as phosphate donor, 2 mol phosphate per mol enzyme [12] <25> autophosphorylation and phosphorylation of histone Hl [19] <31> strong preference for d-enantiomers of antiviral nucleotide analogs like ddATP, ddCTP, 3 -deoxy-3 -thymidine, 2 ,3 -didehydro-2 ,3 -dideoxythymidine [50]) [12, 19, 50]... 

Williams, R.L. Oren, D.A. Munoz-Dorado, J. Inoue, S. Inoue, M. Arnold, E. Crystal structure of Myxococcus xanthus nucleoside diphosphate kinase and its interaction with a nucleotide substrate at 2.0 A resolution. J. Mol. Biol., 234, 1230-1247 (1993)... 

Gonin, P. Xu, Y Milon, L. Dabernat, S. Morr, M. Kumar, R. Lacombe, M.L. Janin, J. Lascu, I. Catalytic mechanism of nucleoside diphosphate kinase investigated using nucleotide analogues, viscosity effects, and X-ray crystallography. Biochemistry, 38, 7265-7272 (1999)... 

Chen, Y Gallois-Montbrun, S. Schneider, B. Veron, M. Morera, S. Deville-Bonne, D. Janin, J. Nucleotide binding to nucleoside diphosphate kinases X-ray structure of human NDPK-A in complex with ADP and comparison to protein kinases. J. Mol. Biol., 332, 915-926 (2003)... 

Prinz, H. Lavie, A. Scheidig, A.J. Spangenberg, O. Konrad, M. Binding of nucleotides to guanylate kinase, p21(ras), and nucleoside-diphosphate kinase studied by nano-electrospray mass spectrometry. J. Biol. Chem., 274, 35337-35342 (1999)... 

ATP is the primary high-energy phosphate compound produced by catabolism, in the processes of glycolysis, oxidative phosphorylation, and, in photosynthetic cells, photophosphorylation. Several enzymes then cany phosphoryl groups from ATP to the other nucleotides. Nucleoside diphosphate kinase, found in all cells, catalyzes the reaction... 

Most kinases transfer chiral phospho groups with inversion and fail to catalyze partial exchange reactions that would indicate phosphoenzyme intermediates. However, nucleoside diphosphate kinase contains an active site histidine which is phosphorylated to form a phosphoenzyme.869 The enzyme catalyzes phosphorylation of nucleoside diphosphates other than ADP by a nucleotide triphosphate, usually ATP. 

Choline and ethanolamine are activated in much the same way as are sugars. For example, choline can be phosphorylated using ATP (Eq. 17-58, step a) and the phosphocholine formed can be further converted (Eq. 17-58, step b) to cytidine diphosphate choline. Phosphocholine is transferred from the latter onto a suitable acceptor to form the final product (Eq. 17-58, step c). Tire polymerization pattern differs from that for polysaccharide synthesis. When the sugar nucleotides react, the entire nucleoside diphosphate is eliminated (Eq. 17-56), but CDP-choline and CDP-ethanolamine react with elimination of CMP (Eq. 

The role of the nucleoside triphosphate in the hydrolysis of DNA has not yet been clarified. ATP and dATP are the most effective nucleotides and only slight activity (10% or less) is observed with the other triphosphates nucleoside diphosphates are inactive. The rate of DNA hydrolysis is proportional to the ATP concentration and the ATP is converted to ADP and inorganic phosphate in the course of the reaction. Three moles of ATP are consumed for each phosphodiester bond cleaved, indicating a complex mechanism of participation of ATP in the endonucleolytic reaction. Preliminary experiments by Takagi and his colleagues indicate that the purified enzyme catalyzes an exchange of ADP with ATP in the absence of DNA, suggesting that a phospho enzyme may be an intermediate. 

Derivatives bearing a 3 -monopbosphoryl group were originally classified as totally resistant to venom exonuclease. As the quality of the enzyme preparation improved, these compounds were found susceptible but required 1000-fold more enzyme than was needed to hydrolyze 5 -monophosphate-bearing compounds. This unusual resistance led to another erroneous conclusion, that the polarity of exonuclease changes (20). The basis for this belief were the experiments in which a mixture of tri-, tetra-, and pentanucleotides of the type d-N pNPpN pN p were used as substrates. The early products were nucleosides and nucleotides, whereas 3, 5 -mononucleoside diphosphates appeared considerably later. It is clear now that the mixture was contaminated with a small amount of dephosphorylated chains which were rapidly hydrolyzed to completion. 

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