Xanthines uracils

NH2-6-NO-uracil Xanthine HCONH2/Na2S204 55CB1306 57JA1518... 

Figure 12 Gradient separation of bases, nucleosides and nucleoside mono- and polyphosphates. Column 0.6 x 45 cm. Aminex A-14 (20 3 p) in the chloride form. Eluent 0.1 M 2-methyl-2-amino-l-propanol delivered in a gradient from pH 9.9-100 mM NaCl to pH 10.0-400 mM NaCl. Flow rate 100 ml/hr. Temperature 55°C. Detection UV at 254 nm. Abbreviations (Cyt) cytosine, (Cyd) cytidine, (Ado) adenosine, (Urd) uridine, (Thyd) thymidine, (Ura) uracil, (CMP) cytidine monophosphate, (Gua) guanine, (Guo) guanosine, (Xan) xanthine, (Hyp) hypoxanthine, (Ino) inosine, (Ade) adenosine, (UMP) uridine monophosphate, (CDP) cytidine diphosphate, (AMP) adenosine monophosphate, (GMP) guanosine monophosphate, (IMP) inosine monophosphate, (CTP) cytidine triphosphate, (ADP) adenosine diphosphate, (UDP) uridine monophosphate, (GDP) guanosine diphosphate, (UTP) uridine triphosphate, (ATP) adenosine triphosphate, (GTP), guanosine triphosphate. (Reproduced with permission of Elsevier Science from Floridi, A., Palmerini, C. A., and Fini, C., /. Chromatogr., 138, 203, 1977.)...

The DNA bases that contain amino groups tend to deaminate spontaneously. In particular, cytosine significantly deaminates to uracil, but adenine and guanine can also deaminate to hypoxanthine and xanthine, respectively. If not corrected, the new bases can cause serious mutations... 

In the early days of meteorite analysis, it was difficult to detect N-heterocycles later, the Murchison meteorite was shown to contain xanthine, hypoxanthine, guanine, adenine and uracil (about 1.3 ppm in total). This meteorite seems to contain various classes of basic and neutral N-heterocycles, as well as isomeric alkyl derivatives. 

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

HNO2 converts — NH2 to —OH, i.e., cytosine to uracil and guanine to xanthine via diazotization, thereby changing the genetic code and leading possible mutation. 

Abnormal bases (uracil, hypoxanthine, xanthine) alkylated bases in some other organisms, pyrimidine dimers... 

Purines and pyrimidines, 7.5 X 10"6 molar solution of adenine, guanine, xanthine, uric acid, uracil, cytosine, thymine. 

Cytosine (2-hydroxy-6-amino-pyrimidine), uracil (2,6-dihydroxypyrimidine), and thymine (5-methyluracil) are pyrimidine derivatives adenine (6-aminopurine), guanine (2-amino-6-hy-droxypurine), and xanthine (2,6-dihydroxypurine) are purine derivatives (Fig. 5). 

An alternative to the terrestrial synthesis of the nucleobases is to invoke interstellar chemistry. Martins has shown, using an analysis of the isotopic abundance of 13C, that a sample of the 4.6 billion year old Murchison meteorite which fell in Australia in 1969 contains traces of uracil and a pyrimidine derivative, xanthine. Samples of soil that surrounded the meteor when it was retrieved were also analyzed. They gave completely different results for uracil, consistent with its expected terrestrial origin, and xanthine was undetectable [48], The isotopic distributions of carbon clearly ruled out terrestrial contamination as a source of the organic compounds present in the meteorite. At 0°C and neutral pH cytosine slowly decomposes to uracil and guanine decomposes to xanthine so both compounds could be the decomposition products of DNA or RNA nucleobases. They must have either travelled with the meteorite from its extraterrestrial origin or been formed from components present in the meteorite and others encountered on its journey to Earth. Either way, delivery of nucleobases to a prebiotic Earth could plausibly have been undertaken by meteors. The conditions that formed the bases need not have been those of an early Earth at all but of a far more hostile environment elsewhere in the Solar System. That environment may have been conducive to the production of individual bases but they may never have been able to form stable DNA or RNA polymers this development may have required the less extreme conditions prevalent on Earth. 

Some chemical fragments of DNA and RNA can also be found in meteorites (Tables 5.1 and 5.2). For example, some meteorites have been reported to contain small amounts of adenine, one of the nucleobases found in RNA and DNA. The current view is that the Murchison meteorite contained adenine, guanine, their hydrolysis products hypoxanthine and xanthine, and uracil. The reported concentration of all those substances, however, is low, about 1.3 ppm. The Murchison and other meteorites may also contain ribitol and ribonic acid, the reduced and oxidized forms of ribose, respectively, but ribose itself has not been found.6... 

The major bases found in nucleic acids are adenine and guanine (purines) and uracil, cytosine, and thymine (pyrimidines). Thymine is found primarily in DNA, uracil in RNA, and the others in both DNA and RNA. Their structures, along with their chemical parent compounds, purine and pyrimidine, are shown in Figure 10.1, which also indicates other biologically important purines that are not components of nucleic acids. Hypoxanthine, orotic acid, and xanthine are biosynthetic and/or degradation intermediates of purine and pyrimidine bases, whereas xanthine derivatives—caffeine, theophylline, and theobromine—are alkaloids from plant sources. Caffeine is a component of coffee beans and tea, and its effects on metabolism are mentioned in Chapter 16. Theophylline is found in tea and is used therapeutically in asthma, because it is a smooth muscle relaxant. Theobromine is found in chocolate. It is a diuretic, heart stimulant, and vasodilator. 

Xanthine does not react with PRPP. ATP reacts in the formation of carbamoyl phosphate, orotic acid in the pyrimidine pathway, and uracil and hypoxanthine in the salvage reactions. 

Aldehyde Oxidase. This enzyme is usually found in similar locations to xanthine oxidase or dehydrogenase and has been isolated from insects, birds, and mammals (20, 21). Aldehyde oxidase seems to be a poor choice of name for this enzyme because, while it oxidizes aldehydes to carboxylic acids, it also accepts a variety of purines and pyrimidines as oxidizable substrates. For example, aldehyde oxidase catalyzes the conversion of 2-hydroxypyrimidine to uracil and of adenine to 8-hydroxy-adenine (25). It appears that xanthine oxidase and aldehyde oxidase are... 

FIGURE 7-5. A 0 to 10% gradient separation of polar compounds. Components (1.0 p.g each) (1) uracil, (2) hypoxanthine, (3) 3-methyl xanthine, (4) theobromine, (5) theophylline, and (6) /3-hydroxyethyl theophylline. Solvent A 0.01 M sodium ace-tate/water. Solvent B acetonitrile. Flow rate 2.0 mL/min. Gradient 0-10% solvent B using a linear shape (top line). Run time 50 min. Injection volume 15 p.L. Column Radial-Pak Resolve Cig (10 /xm) 8 mm ID x 10 cm. Detector UV at 254 nm, 0.1 AUFS. (Reproduced from reference 1 with permission.)... 

Fig. 15.2 a -d. Formulas of some modified bases occurring naturally in transfer RNA s. a Hypo-xanthine, a guanine derivative lacking the 2-amino group b dihydrouracil and c 4-thiouracil, two derivatives of uracil d 1-methyladenine, a positively charged derivative of adenine... 

Adenine, guanine, guanylurea, and several s-triazines and ureas have been detected in HCl-extracts of Orgueil and Murchison (Hayatsu, 1964 Hayatsu et al, 1968, 1975). The first 3 were confirmed by Stoks and Schwartz (1981), but the s-triazines were not they may have formed from guanylurea in the isolation and identification procedure. Other compounds detected are xanthine, hypoxanthine, and uracil (van der Velden and Schwartz, 1977 Stoks and Schwartz, 1979). A report of 4-hydroxy-pyrimidine and several related compounds (Folsorae et al, 1973) was not confirmed (Hayatsu et al, 1975 van der Velden and Schwartz, 1977) these compounds, which... 

Thus, uracil 223 is converted by N-phenylphosphoric acid triamide in 46% yield into 2,4-bis-phenylaminopyrimidine (224), whereas HMPA aminates uracil 223 to the 2,4-bis-dimethylaminopyrimidine (225) in 78% yield (70IZV904). The amination of xanthine 226 by HMPA furnishes 79% of 2,6-bis-(dimethylamino)purine (227) (701ZV953). 

Purines and Pyrimidines (fig. 7.1), are best known as building blocks of RNA (ribonucleic acid) and DNA (deoxyribonucleic acid). Adenine and guanine are purine bases (so are xanthine and hypoxanthine, but these are reaction intermediates and are not part of the DNA or RNA molecule). Cytosine, uracil, and thymine are pyrimidine bases. 

In the early attempts to identify the nitrogenous bases of desoxy-ribosenucleic acid, some confusion arose for two reasons. At first, the products obtained by hydrolysis of nucleoprotein were studied, and there was no assurance that any particular base came from the nucleic acid rather than from the protein. Then, when the nucleic acid itself became available, the hydrolytic agents at first employed were sufficiently drastic to cause some deamination of the amino-purines (with the production of some xanthine and hypoxanthine) and some demethylation of thymine to uracil. In 1874, Piccard isolated guanine (and h3T>oxanthine) from sperm nuclein. Kossel and Neumann discovered in the hydrolysate of thymus nucleic acid two new pyrimidine bases which they named thy-mine and cytosine but they assigned incorrect empirical formulas to them. In 1894, they correctly described thymine as CsHgOjNs, but cytosine was not purified and characterized till much later. " " Levene now analyzed a series of nucleic acids from a variety of sources and found " that they all contained guanine and adenine. By mild hydrolysis of thymus nucleic acid, Steudel obtained guanine and adenine as the sole purine bases and demonstrated that they occur in equi-molecular proportions. Levene and Mandel confirmed this result and showed that the two purine bases and the two pyrimidine bases (thymine and cytosine) all occur in thymus nucleic acid in equimolecular proportions. 

Fig. 7. (A) Pyrimidine metabolism m vitro in human epidermis. C, eytidine U, uracil T, thymine O, orotic acid R, ribose dR, deoxyribose MP, monophosphate. (B) Purine metabolism in vitro in human epidermis. A, adenine G, guanine H, hypoxanthine X, xanthine UA, uric acid I, inosine R, ribose dR, deoxyribose MP, monophosphate. In (A) and (B), dotted line indicates reaction not found. Adapted from de Bersaques (B15).

N2O3 formed by a third order reaction, can deaminate DNA bases yielding uracil from cytosine, xanthine from guanine, methyl cytosine from thymine and hypoxanthine from adenine [ 56 ]. Furthermore, it can react with secondary amines to yield carcinogenic N-nitrosoamines, which can damage DNA by alkylation, [57]. 

---