Hydrolysis of Nucleosides

The ligation reactions catalyzed by ligases ( synthetases, class 6) are energy-dependent and are therefore always coupled to the hydrolysis of nucleoside triphosphates. 

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

The enzyme splitting both adenosine-tetraphosphate and guanosine-tetraphosphate was purified to homogeneity from yellow lupin seeds (Guranowski et al., 1997). The polypeptide of 25 kDa catalysed the hydrolysis of nucleoside-5 -tetraphosphate to nucleoside triphosphate and P , and hydrolysed PolyP3, but neither pyrophosphate nor PolyPs The divalent carions Mg2+, Co2+, Ni2+ or Mn2+ were required for the reaction. 

Glycosylases Catalyze hydrolysis of nucleoside bases-glycosidic bonds, resulting in production of an apurinic/ apyrimidinic (AP) site in DNA and a free nucleoside base ... 

The RNA helicase activity of the full-length NS3/4A enzyme (8) and of the NS3 C-terminal helicase domain has been demonstrated (10,11,17-19) by the unwinding of double-stranded RNA (dsRNA) molecules. The directionality of RNA helicase unwinding is 3 to 5 with respect to the template strand (8,19). Unlike most other helicases, the HCV NS3 helicase is capable of unwinding both RNA and DNA homoduplex and heteroduplex molecules (19). In common with other helicases, NS3 helicase requires divalent cations (Mg2+ or Mn2+) in conjunction with the hydrolysis of nucleoside triphosphates (NTPs) to provide the energy source for unwinding (11,12). 

Some biosynthetic reactions are driven by the hydrolysis of nucleoside triphosphates that are analogous to ATP—namely, guanosine triphosphate (GTl ), uridine triphosphate (UTP), and cytidine triphosphate (CTP). The diphosphate forms of these nucleotides are denoted by GDP, UDP, and CDP, and the monophosphate forms are denoted by GMP, UMP, and CMP. Enzymes catalyze the transfer of the terminal phosphoryl group from one nucleotide to another. The phosphorylation of nucleoside monophosphates is catalyzed by a family of nucleoside monophosphate kinases, as discussed in Section 9.4. The phosphorylation of nucleoside diphosphates is catalyzed by 7iucleoside diphosphate kinase, an enzyme with broad... 

In any event, it is clear that further study of the hydrolysis of nucleoside 3 5 -cyclic phosphates is necessary. It also remains to be explained why the 3 5 -cyclic phosphates of adenosine and guanosine are more resistant to glycosyl cleavage in acid than are the corresponding 5 -phosphates or nucleosides. 

Synthesis of a phosphodiester bond in nucleic acids requires energy input. As a result, the nucleoside monophosphates in nucleic acids are built up from hydrolysis of nucleoside triphosphates. Cleaving a pyrophosphate from a nucleoside triphosphate yields a nucleoside monophosphate and enough free energy to make the formation of polynucleoside monophosphates (i.e., polynucleotides) thermodynamically favorable. 

This enzyme is an alkaline phosphomonoesterase that catalyzes the hydrolysis of nucleoside 5 -monophosphates (e.g., adenosine-5 -monophosphate and inosine-5 -monophosphate). It appears to be distributed widely in the body tissues and to be mainly a membrane-bound enzyme, but it is also found in the cytoplasm, lysosomes, and other subcellular organelles. In the liver, the enzyme is located on the bile canicular membrane and on other cells, including the sinusoidal cells, leading to its use for the detection of hepatobiliary injury (Goldberg 1973 Dooley and Racich 1980 Carakostas, Power, and Banerjee 1990 Sunderman 1990). The enzyme measurement has largely been discarded in clinical medicine however, more recently, the 5 -NT enzymes have been implicated in the inhibition of antiviral nucleosides, so interest may be revived (Hunsucker, Mitchell, and Spychala 2005). 

These cyclic phosphates are intermediates in the enzymic and alkaline degradation of ribonucleic acids, and may be the activated intermediates for the enzymic synthesis of ribonucleic acids from the nucleotides 175), Enzymes specific for the hydrolysis of nucleoside 2,3-cyclic phosphates to the monoesters have been prepared from snake venom, spleen, and intestinal mucosa. (See Chapter VIII.)... 

Two groups have reported the synthesis of compounds of type (139) as potential models for ring-opening reactions of cyclic AMP. These studies included cases where the dioxaphosphorinane ring was both apical-equatorial and diequatorial, and conformations were studied by n.m.r.i98,i99 xhe predominant formation of 3 -monophosphates in the base-catalysed hydrolysis of nucleoside 3, 5 -cyclic phosphates has been interpreted in terms of the lone pair orientation effect, which may decrease the energy of the transition state for P-O bond-breaking.200 Conformational studies have been carried out on the diastereomers of adenosine cyclic 3 ,5 -phosphorothioate, where chair conformations predominate, and for the / p-isomer of deoxyadenosine cyclic phosphoranilidate, where a chair-twist equilibrium... 

A review has been published on the acidic hydrolysis of nucleosides and nucleotides, particularly with regard to the influence of sugar and base substitutions on the stability of the JV-glycosidic bond.243 First-order rate... 

The unfavorable equilibrium condition of Eq. (67) can be overcome by coupling this reaction to what is equivalent to the hydrolysis of nucleoside triphosphate [Eq. (68)]. Here the reaction proceeds completely and irreversibly toward hydrolysis and is capable of pulling reactions to which it is coupled. 

Finlayson, B. Taylor, E. W. (1969). Hydrolysis of nucleoside triphosphates by myosin during the transient state. Biochemistry, 8,802-10. 

Partial hydrolysis of nucleoside phosphorodifluoridates (Scheme 3) proceeds in a very high yield (8). The preparation of nucleosid-3 -yl or 5 -yl phosphorodifluoridates is described elsewhere in this chapter. 

An excellent review concerned with the metal-ion-promoted hydrolysis of nucleoside S -triphosphates has appeared. Although most of the metal-accelerated reactions of phosphates involve cobalt(III), Sargeson has recently described some reactions of iridium(III) complexes. The hydrolysis of [(H3N)5lr0P)(=0)(0R)(0Ar)] (Ar = 4-nitrophenyl R = Et or Ar) obeys a two-term rate law (5). It is suggested that the preliminary step is an... 

---