Nucleotides pyrimidine deoxy

In view of the difficulty of hydrolyzing the pyrimidine nucleosidic linkages, ribonucleic acids have been hydrolyzed to a mixture of purine bases and pyrimidine nucleotides which is then separated by paper chromatography.132, 163 164 This method has been employed extensively for the analysis of ribonucleic acids, and gives reproducible results,166 but it has not been used to any great extent for deoxyribonucleic acids, probably because, under these conditions of hydrolysis, they yield some pyrimidine deoxy-ribonucleoside diphosphates.166... 

Fig. 6. P-NMR spectra at 109.3 MHz of sonicated alternating purine-pyrimidine deoxy-nucleotide duplexes A, poly(dAdT)-poly(dAdT) at 24 °C B, poly(dA-br dU)-prfy(dA-br dU) at 30X C, poly(dAdU) poly(dAdU) at 3I C D, poly(dIdC)-poly(dIdC) at 39 C E, poly(dGdC) poly(dGdC)at23 C allin0.1 MNaQand0.05 mAfEDTA,pH6-7,except(B) in S toM Tris and 0.1 laM EDTA. Chemical shifts arc upiield positive from internal TMP. Reproduced with permission, fiom Cohen et al., 1981. Copyright 1981 American Chemical Society.

A nucleoside consists of a purine or pyrimidine base linked to a pentose, either D-ribose to form a ribonucleo-side or 2-deoxy-D-ribose to form a deoxyribonucleoside. Three major purine bases and their corresponding ribo-nucleosides are adenine/adenosine, guanine/guanosine and hypoxanthine/inosine. The three major pyrimidines and their corresponding ribonucleosides are cytosine/ cytodine, uracil/uradine and thymine/thymidine. A nucleotide such as ATP (Fig. 17-1) is a phosphate or polyphosphate ester of a nucleoside. 

PRPP is an "activated pentose" that participates in the synthesis of purines and pyrimidines, and in the salvage of purine bases (see p. 294). Synthesis of PRPP from ATP and ribose 5-phosphate is catalyzed by PRPP synthetase (ribose phosphate pyrophosphokinase, Figure 22.6). This enzyme is activated by inorganic phosphate (Pi) and inhibited by purine nucleotides (end-product inhibition). [Note The sugar moiety of PRPP is ribose, and therefore ribonucleotides are the end products of de novo purine synthesis. When deoxy-ribonucleotides are required for DNA synthesis, the ribose sugar moiety is reduced (see p. 295).]... 

The DNA sugar is 2-deoxy-D-ribose. The four heterocyclic bases in DNA are cytosine, thymine, adenine, and guanine. The first two bases are pyrimidines, and the latter two are purines. In nucleosides, the bases are attached to the anomeric carbon (C-1) of the sugar as p-N-glycosides. In nucleotides, the hydroxyl group (-OH) at C-3 or C-5 of the sugar is present as a phosphate ester. 

Figure 5.1 Deoxyribozyme-catalyzed RNA cleavage. (A) The cleavage reaction, which forms 2,3,-cyclic phosphate and 5-OH RNA termini. (B) Individual deoxy-ribozymes and their target sequences for efficient cleavage of all-RNA substrates. N, any nucleotide R, purine Y, pyrimidine. Outside of the expheidy indicated nucleotides, any RNA sequence is tolerated as long as Watson-Crick RNA DNA covariation is maintained.

The term nucleoside was originally proposed by Levene and Jacobs in 1909 for the carbohydrate derivatives of purines (and, later, of pyrimidines) isolated from the alkaline hydrolyzates of yeast nucleic acid. The phosphate esters of nucleosides are the nucleotides, which, in polymerized forms, constitute the nucleic acids of all cells.2 The sugar moieties of nucleosides derived from the nucleic acids have been shown, thus far, to be either D-ribose or 2-deoxy-D-eri/fAro-pentose ( 2-deoxy-D-ribose ). The ribo-nucleosides are constituents of ribonucleic acids, which occur mainly in the cell cytoplasm whereas 2-deoxyribo -nucleosides are components of deoxypentonucleic acids, which are localized in the cell nucleus.3 The nucleic acids are not limited (in occurrence) to cellular components. They have also been found to be important constituents of plant and animal viruses. 

It was concluded39 from these studies that the two nucleotides obtained by enzymic hydrolysis of the deoxyribonucleic acid of T2 bacteriophage are 2-deoxy-5 -(hydroxymethyl)cytidylic acid and a glucose derivative thereof. It was also concluded that the glucose residue is affixed to the pyrimidine portion of the nucleotide and nucleoside of 5-(hydroxymethyl)-cytosine and, on the basis of the near identity of the spectra of the two nucleotides of 5-(hydroxymethyl)cytosine, it was suggested that the hexose is attached to the hydroxymethyl group of the pyrimidine. 

The reaction of hydrated electrons formed by radiolysis with peroxydisulfate yields the sulfate radical anion SO4 which is a strong chemical oxidant (Eqx = 2.4 V/NHE) [50, 58]. The oxidation of both purine and pyrimidine nucleotides by S04 occurs with rate constants near the diffusion-controlled limit (2.1-4.1 x 10 M s ). Candeias and Steenken [58a] employed absorption spectroscopy to investigate acid-base properties of the guanosine cation radical formed by this technique. The cation radical has a pKa of 3.9, and is rapidly deprotonated at neutral pH to yield the neutral G(-H) . Both G+ and G(-H) have broad featureless absorption spectra with extinction coefffcients <2000 at wavelengths longer than 350 nm. This has hampered the use of transient absorption spectra to study their formation and decay. Candeias and Steenken [58b] have also studied the oxidation of di(deoxy)nucleoside phosphates which contain guanine and one of the other three nucleobases by SO4 , and observe only the formation of G+ under acidic conditions and G(-H) under neutral conditions. 

Purines, pyrimidines and their nucleosides and nucleoside triphosphates are synthesized in the cytoplasm. At this stage the antifolate drugs (sulphonamides and dihydrofolate reductase inhibitors) act by interfering with the synthesis and recycling of the co-factor dihydrofolic acid (DHF). Thymidylic acid (2-deoxy-thymidine monophosphate, dTMP) is an essential nucleotide precursor of DNA synthesis. It is produced by the enzyme thymidylate synthetase by transfer of a methyl group from tetrahydrofolic acid (THF) to the uracil base on uridylic acid (2-deoxyuridine monophosphate, dUMP) (Fig. 12.5). THF is converted to DHF in this process and must be reverted to THF by the enzyme dihydrofolate reductase (DHFR) before... 

All the pyrimidine nucleotides can proceed to the deoxy compounds as diphosphates, similar to the purines. However, uridine does not occur in DNA therefore, it must be converted to a thymine derivative. This occurs by the following basic pathway CDP is converted to dCDP. This is converted to dCMP, which can produce dUMP. The dUMP is then methylated in the number 5 position, via N5, N10-methylene tetrahydrofolate. This produces deoxythymidine monophosphate (dTMP) and dihydrofolate. The dTMP then can be converted to dTDP and dTTP, which can be incorporated into DNA (Fig. 20.9). 

The essential elements of Table 2.1 meet these demands. In all cases they are components of the metabolic system in cell or of important final products for example, cellulose for the upright standing of the plant. The function as constituents of such compounds is clear for C, H, and O. These three elements are together components of nearly all organic compounds in the plant [only hydrocarbons (e.g., carotins) are free of O], and therefore they build up the planfs shape. A similarly clear situation holds true for N and P, both of which are constituents of the information carriers DNA and RNA. N is a component of their purine and pyrimidine bases, while phosphoric acid esters of D-ribose or 2-deoxy-D-ribose form the backbone of their nucleotide sequences. Moreover, P plays a very important role in energy metabolism, the key compounds being nucleotide phosphates (e.g., adenosine triphosphate, ATP) (see Scheme 2.1) and the homologous molecules... 

Nucleotides are derived from three different types of molecules—phosphoric acid, pentose sugar, and heterocyclic nitrogen base (Fig. 21-1). Two different pentoses are used, o-ribose for RNA and 2-deoxy-D-ribose for DNA. Henceforth, the sugars will be referred to simply as ribose and deoxyri-bose. A total of five different heterocyclic bases are used, three pyrimidine and two purine bases. Each base is symbolized by the first letter of its name, C, T, U, A, and G for cytosine, thymine, uracil, adenine, and guanine, respectively. A, G, and C are used in synthesizing both DNA and RNA nucleotides. T is used only for DNA while U is used only for RNA. 

DNA is not normally broken down, except after cell death and during DNA repair. RNA is turned over in much the same way as protein. The enzymes involved in breaking down both types of polynucleotides are the nucleases, or more specifically deoxy-ribonucleases and ribonucleases, they hydrolyze DNA and RNA, respectively, to oligo-nucleotides which can be further hydrolyzed (Fig. 14-38) so eventually purines and pyrimidines are formed. 

In ribonucleotides, the pentose is the o-ribose while in deoxyribonucleotides, the sugar is 2 -deoxy-D-ribose. The nitrogen base of the planar, heterocyclic molecule derived from purine or pyrimidine is linked to Cl of the sugar residue. The phosphate group may be bonded to the C3 or C5 of a pentose to form its 3 -nucleotide or its 5 -nucleotide respectively. In nucleic acids, the purine and pyrimidine bases of nucleotides serve solely as information symbols for the coding of genetic information. 

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