Nucleoside 5’-diphosphates

NAD GLYCOHYDROLASE Hydrolysis of nucleoside diphosphate, NUCLEOSIDE DIPHOSPHATASE Hydrolysis of 3 -ribonucleotide,... 

Base Sugar Nucleosidea (base + sugar) Nucleoside Monophosphateb Nucleoside Diphosphate Nucleoside Triphosphate... 

Synthetic oligonucleotides may be used as "primers and be elongated stepwise with the aid of polynucleotide phosphorylase (PNPase) and nucleoside diphosphates. 

Nucleoside 5 -diphosphates (NDPs) and nucleoside 5 -triphosphates (NTPs)... 

FIGURE 23.6 The PEP carboxykinase reaction. GTP formed in this reaction can be converted to ATP by nucleoside diphosphate kinase, althongh liver cells in some species may not contain this enzyme. 

Azathymidine was first prepared by Prusoff " and the procedure was described in more detail by Hall and Haselkorn. The nucleoside was prepared here in the form of a glassy solid, but with dibenzyl-phosphochloridate it yielded a mixture of nucleotides from which crystalline 3 -phosphate, 5 -phosphate, and 3, 5 -diphosphate were prepared. 

The NDP-dependent potassium (KndP) channel is activated by nucleoside diphosphates (NDPs) in the presence of Mg2+ and is relatively insensitive to inhibition by ATP. Kndp channels are present in vascular smooth muscle. 

All NRTIs, as exemplified for AZT (Fig. 7), act in a similar fashion following their uptake by the cells, they are phosphorylated successively to their 5 -monophosphate, 5 -diphosphate, and 5 -triphosphate form (De Clercq 2002). Unlike the first phosphorylation step in the metabolic pathway of the acyclic guanosine analogues (see above), which is carried out by a virus-encoded enzyme (thymidine kinase), the first as well as the subsequent phosphorylations of the 2, 3 -dideoxynucleosides are carried out by cellular enzymes, that is, a 2 -deoxynucleoside (e.g., dThd) kinase, a 2 -deoxynucleotide (e.g., dTMP) kinase, and a (2 -deoxy)nucleoside 5 -diphosphate (NDP) kinase. 

Entecavir, telbivudine, clevudine, and the other nucleoside analogues (Fig. 4aa) need to be phosphorylated to their 5 -triphosphate form to be antivirally active (Fig. 8). This again implies three phosphorylation steps based successively on a nucleoside kinase, nucleoside 5 -monophosphate kinase, and nucleoside 5 -diphosphate kinase. These reactions have been characterized only in a few cases, that is, thymidylate kinase in the metabolism of clevudine (Hu et al. 2005). 

For most of the sugar components, little or nothing is known about their biosynthesis. Nucleoside hexosyl-4-ulose diphosphates are, however, almost certainly key intermediates in the biosynthesis of several of these sugars, as discussed in Ref 7. The biosynthesis of the 6-deoxyheptoses is probably analogous to that of the 6-deoxyhexoses, and proceeds by way of nucleoside heptosyl-4-ulose diphosphates. 

By means of the enzyme nucleoside diphosphate kinase, UTP, GTP, and CTP can be synthesized from their diphosphates, eg,... 

All of these triphosphates take part in phosphorylations in the cell. Similarly, specific nucleoside monophosphate kinases catalyze the formation of nucleoside diphosphates from the corresponding monophosphates. 

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. 

A primed numeral locates the position of the phosphate on the sugars of mononucleotides (eg, 3 -GMP, 5 -dCMP). Additional phosphoryi groups linked to the first by acid anhydride bonds form nucleoside diphosphates and triphosphates. 

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). 

Most nucleotide sugars are formed in the cytosol, generally from reactions involving the corresponding nucleoside triphosphate. GMP-sialic acids are formed in the nucleus. Formation of uridine diphosphate galactose (UDP-Gal) requires the following two reactions in mammahan tissues ... 

When AMP is heated under reflux in DMF, the 2, 3 -cyclic phosphate is formed, and cyclic phosphates can also be obtained from nucleosides and ortho-, pyro-, or poly-phosphoric acids under the same conditions. Promotion of phosphorylation by DMF is well known and the reaction with AMP is probably intermolecular as no 3, 5 -cyclic AMP can be detected. Minor products in the latter reaction are the 2, 3 -cyclic 5 -diphosphate and the 2 (30,5 -diphosphate. The synthesis of adenosine 2 (3 )-phosphate 5 -pyrophosphate has been achieved by the phosphoromorpholidate method used in a synthesis of Co A. ... 

C. Nucleoside Diphosphate Sugars.—A polyprenol phosphate containing eleven isoprene units is involved in the biosynthesis of various bacterial cell-wall components.As mentioned in last year s Report, another isoprenoid phosphate, dolichol monophosphate (40), is an intermediate in sugar... 

NCF Neutrophil chemotactic factor NDGA Nordihydroguaretic acid NDP Nucleoside diphosphate Neca 5 -(N-ethyl carboxamido)-adenosine NED Nedocromil sodium NEP Neutral endopeptidase (EC 3.4.24.11)... 

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