Uracil, from nucleic acids

Any one nucleotide, the basic building block of a nucleic acid, is derived from a molecule of phosphoric acid, a molecule of a sugar (either deoxyribose or ribose), and a molecule of one of five nitrogen compounds (bases) cytosine (C), thymine (T), adenine (A), guanine (G), uracil (U). 

The bases that occur in nucleic acids are aromatic heterocyclic compounds derived from either pyrimidine or purine. Five of these bases are the main components of nucleic acids in all living creatures. The purine bases adenine (abbreviation Ade, not A ) and guanine (Gua) and the pyrimidine base cytosine (Cyt) are present in both RNA and DNA. In contrast, uracil (Ura) is only found in RNA. In DNA, uracil is replaced by thymine (Thy), the 5-methyl derivative of uracil. 5-methylcyto-sine also occurs in small amounts in the DNA of the higher animals. A large number of other modified bases occur in tRNA (see p. 82) and in other types of RNA. 

In DNA the sugar molecule in the nucleotide is 2-deoxyribose, and in RNA it is ribose. The amine bases in DNA are adenine, thymine, cytosine, and guanine, symbolized by A, T, C, and G, respectively. RNA contains adenine, cytosine, and guanine, but thymine is replaced by the based uracil (Figure 16.16). The primary structure of nucleic acids is given by the sequence of the amine side chains starting from the phosphate end of the nucleotide. For example, a DNA sequence may be -T-A-A-G-C-T. 

As with proteins, the nucleic acid polymers can denature, and they have secondary structure. In DNA, two nucleic acid polymer chains are twisted together with their bases facing inward to form a double helix. In doing so, the bases shield their hydrophobic components from the solvent, and they form hydrogen bonds in one of only two specific patterns, called base pairs. Adenine hydrogen bonds only with thymine (or uracil in RNA), and guanine pairs only with cytosine. Essentially every base is part of a base pair in DNA, but only some of the bases in RNA are paired. The double-helix structure... 

Cytosine and thymine were first isolated by hydrolysis of calf thymus tissue by Albrecht Kossel (1853-1927) and A. Neumann during 1893-1894. Thymine s structure was published in 1900 and confirmed over the next several years when it was synthesized by several investigators. In 1903, cytosine was synthesized by Henry Lord Wheeler (1867-1914) and Treat B. Johnson, confirming its structure. Uracil was first isolated in 1900 from yeast nucleic acid found in bovine thymus and herring sperm. The methylation of uracil produces thymine thymine is also called 5-methyluracil because methylation takes place at the fifth carbon in uracil to produce thymine. 

If the terminal pyrophosphate is removed from a molecule of ATP, the remainder is AMP, adenosine monophosphate, one of the four building blocks of the important biological macromolecules, the nucleic acids. There are two types of nucleic acids (26) ribonucleic acid (RNA), and deoxyribonucleic acid (DNA). RNA is a polymer of four different nucleotides, one of which is AMP, the ribose phosphate of adenine. The other three nucleotides are also ribose phosphates of heterocyclic bases, guanine, cytosine, and uracil. The structure of the four bases is shown in Figure 6. 

Figure 6.44 Replication of a nucleic acid in the presence of the base analogue bro mo uracil. After the first replication, Bu enters opposite G, giving a ""I G C->A T transition. If G enters opposite Bu already C r, incorporated, an A T—>G C transition results. Abbre-4 gu viations Bu, bromouracil G, guanine. Source 4 Bu Adapted from Ref. 12.

Two types of heterocyclic N bases are found the pyrimidine bases (31), (32) and (33), and the purine bases (34) and (35). The pKt values are given in Table 10 as are the names of the compounds derived from the bases. One other difference between DNA and RNA is that the former is found to contain thymine, while the latter contains uracil. The average cell contains 2-5% of its dry weight as nucleic acids and nucleotides neither the heterocyclic bases nor the nucleosides occur as such in cells. 

The study of nucleic acid bases by NMR has been reported in a number of monographs (/), but very little data is available on the, 3C and, 5N NMR chemical shift tensors in these compounds. The low sensitivity of NMR spectroscopy and the long relaxation times exhibited by many of these compounds have posed the main impediments for these studies. The use of sample doping with free radical relaxation reagents, to reduce the relaxation times facilitating 2D multiple pulse experiment (2, 3), enables one to measure and analyze the principal values of the chemical shift tensors in natural abundance samples. In previous papers from this laboratory we have presented, 5N NMR chemical shift principal values for adenine, guanine, cytosine, thymine and uracil (4, 5). 

Orotic acid (uracil-6-carboxylic acid), first isolated147 from milk, has been amply demonstrated to be an effective precursor of nucleic acid and nu-... 

A number of studies on photochemistry of the nucleic acid bases in aqueous solutions demonstrated that while uracil undergoes reversible hydration under exposure to UV irradiation, the other bases (thymine, adenine, and guanine) were stable [41,42], However, the sensitivity of dissolved thymine to UV irradiation can be significantly increased if the solution is rapidly frozen [43]. In 1960 the thymine photoproduct was isolated from irradiated frozen aqueous solution of thymine. Elemental analysis, molecular weight measurements, powder X-ray diffraction, NMR and IR spectroscopy confirmed that the most likely photoproduct is a thymine dimer [20]. Similar photoproduct was obtained by hydrolysis of irradiated DNA. Its formation was attributed to reaction between two adjacent thymine groups on the same DNA chain [44], Independently an identical compound was isolated from DNA of UV-irradiated bacteria [45]. 

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