5 -phosphate deoxyribonucleotides

Cytosine was isolated from hydrolysis of calf thymus in 1894 and by 1903 its structure was known and it had been synthesized from 2-ethylthiopyrimidin-4(3H)-one. The acid hydrolysis of ribonucleic acid gives nucleotides, among which are two cytidylic acids, 2 -and 3 -phosphates of cytidine further hydrolysis gives cytidine itself, i.e. the 1-/3-D-ribofuranoside of cytosine, and thence cytosine. The deoxyribonucleic acids likewise yield deoxyribonucleotides, including cytosine deoxyribose-5 -phosphate, from which the phosphate may be removed to give cytosine deoxyriboside and thence cytosine. 

Deoxyribonucleic acid (DNA) (Section 28.1) The biopolymer consisting of deoxyribonucleotide units linked together through phosphate-sugar bonds. Found in the nucleus of cells, DNA contains an organism s genetic information. 

RNA is as suitable (if not more so) than DNA as a cleavage target [37]. In contrast to DNA, RNA is substantially less prone to oxidative cleavage [38] as a consequence of the higher stability of the glycosidic bond in ribonucleotides compared to that in deoxyribonucleotides. On the basis of the properties described in the introductory sections RNA is by contrast, much less stable to hydrolytic cleavage. For this reason the hydrolysis of the phosphate bond in this system can be successfully catalyzed not only by metal ions but also by ammonium ions. 

The 3, 5 intemucleotide linkage is formed either by condensing die 3 -hydroxy group of an appropriately protected deoxyribonucleotide or -nucleoside with the 5 -phosphate of a deoxyribonucleotide (method a), or by condensing a 3 -phosphordiester with the 5 -hydroxy group of a nucleoside in a modified phosphortriester approach (method b). 

The deoxyribonucleotides, except for deoxythymidine nucleotide, are formed from the ribonucleotides by the action of an enzyme complex, which comprises two enzymes, ribonucleoside diphosphate reductase and thioredoxin reductase (Figure 20.11). The removal of a hydroxyl group in the ribose part of the molecule is a reduction reaction, which requires NADPH. This is generated in the pentose phosphate pathway. (Note, this pathway is important in proliferating cells not only for generation... 

Figure 20.11 Enzyme complex that converts ribonucleotides to deoxyribonucleotides and role of the pentose phosphate pathway. For details of the pentose phosphate pathway, see Chapter 6, (Appendix 6.8).

The deoxyribonucleotides in the DNA polymer are connected by phosphodi-ester bonds between the 5 -phosphate group attached to one deoxyribose sugar and the 3 -hydroxyl group of the next sugar. 

Figure 25-16 Control of the conversion of inosine 5 -phosphate to the adenine and guanine ribonucleotides and deoxyribonucleotides in bacteria by feedback inhibition and activation.

Fig. 1. Consisting of two helically intertwined strands, ihe DNA molecule is composed of dcoxyribose and phosphate. As shown here, at periodic intervals the sugar-phosphate backbones are joined together by the complementary purine and pyrimidine bases. A single base linked to a deoxyribose-pbosphate moiety constitutes a deoxyribonucleotide. Legend Solid black circles — Thymine Vertical bars = Adenine Horizontal bars = Guanine Dotted circles = Cytosine...

The biosynthetic pathway to UMP starts from carbamoyl phosphate and results in the synthesis of the pyrimidine orotate, to which ribose phosphate is subsequently attached. CTP is subsequently formed from UTP. Deoxyribonucleotides are formed by reduction of ribonucleotides (diphosphates in most cells). Thy-midylate is formed from dUMP. 

Draw the complete structure of deoxycytidine 5 -phosphate, one of the four deoxyribonucleotides. 

The nucleotides of DNA are called deoxyribonucleotides, since they contain the sugar deoxyribose, whereas, those of RNA are called nbonucleotides since they contain nbose instead. Each nucleotide contains both a specific and a nonspecific region. The phosphate and sugar groups are the nonspecific portion of the nucleotide, while the purine and pyrimidine bases make up the specific portion. 

These four bases are incorporated into deoxyribonucleosides and deoxyribonucleotides similar to the bases in ribonucleosides and ribonucleotides. The following structures show the common nucleosides that make up DNA. The corresponding nucleotides are simply the same structures with phosphate groups at the 5 positions. 

The nucleotides are phosphoric acid esters of nucleosides, with phosphate at position C-5. Nucleotides with phosphorylation at other positions are known, but they are not components of the nucleic acids. Nucleotides containing deoxyribose are called deoxyribonucleotides those containing ribose are known as ribonucleotides. 

Adenosine 5 -phosphate is also known as AMP (for adenosine monophosphate) or adenylic acid. If deoxyribose replaces ribose in adenosine 5 -phosphate, the terminology is dAMP or deoxyadenylic acid. The abbreviated names for some ribonucleotides and deoxyribonucleotides are listed below. 

The existence of metal intermediate complexes with deoxynucleotides has been elucidated by Eichhorn et al. (26). Proton NMR spectra of dAMP, dCMP, dGMP and dTMP show, especially for dAMP and dGMP, a strong reaction of Cu2+, although the interaction with the pyrimidines was markedly reduced. Further experiments employing 31P NMR spectroscopy show the broadening of the phosphate resonance of the deoxyribonucleotides of adenine and thymine (26). 

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