Nucleic acid purines

After the nucleic acid purines adenine and guanine, the next most prominent purine in our everyday lives is probably caffeine. Caffeine, in the form of beverages such as tea, coffee, and cola, is one of the most widely consumed and socially accepted natural stimulants. Closely related structurally are theobromine and theophylline. Theobromine is a major constituent of cocoa, and related chocolate products. Caffeine is also used medicinally,... 

Purine bases IC. Computer programs for calculating the relative compositions of nucleotides, nucleic acids, purines. 

The stimulants in tea and coffee are methylated nucleic acid purines... 

Figure 6 is a metabolic map of nucleoprotein catabolism, and Table 6 shows some of the components that can be recovered from scrapings of normal skin, from callus, and from psoriatic scales. In conjunction with the preceding it shows that about 5% of the RNA and less than 1% of the DNA is left in the normal horny layer while up to one-third of the RNA and DNA is still present in the cells of the parakeratotic horny layer of psoriasis. Xanthine and hypoxanthine can be found in psoriatic scales and presumably result from catabolism of nucleic acid purines. Uric acid, although present in the scales, probably comes from the blood, since xanthine oxidase has not been found in human epidermis (B15, B17). Pyrimidine breakdown products have not been found. This might... 

Adenosine was shown to be incorporated into nucleic acid purines, but to only about half the extent of adenine itself (L2). The incorporation of guanosine was also studied and here again the guanine derivative was a poorer precursor than the adenine derivative, but the utilization of guanosine was considerably greater than that of the aglycone (L22). The administration of the adenine nucleotides revealed that these compounds, whether as the 3 isomer or the 5 isomer, were poorer precursors than the free base adenine (Wl). With all nucleotides studied, the incorporation of the 5 isomer was less extensive than of the 3 isomer (R9). Roll et al. have shown that guanine nucleotides are considerably... 

One of the first studies that indicated the possible interference of ametbopterin and aminopterin with purine synthesis was the demonstration by Skipper et al. (S21) that administration of these compounds to mice inhibited the incorporation of labeled formate into nucleic acid purines. Ametbopterin (4-amino-A -methyl-pteroylglutamic acid) has produced some inhibition of uric acid synthesis during the use of this compound for treatment of leukemia (K15, E24). Another inhibitor of... 

A2. Abrams, R., Some factors influencing nucleic acid purine renewal in the rat. Arch. Biochem. Biophys. 33, 436-447 (1951). 

The most important naturally occuring diazines are the pyrimidine bases uracil, thymine and cytosine, which are constituents of the nucleic acids (see 32.4). The nucleic acid pyrimidines are often drawn horizontally transposed from the representations used in this chapter, i.e. with N-3 to the north-west , mainly to draw attention to their structural similarity to the pyrimidine ring of the nucleic acid purines, which are traditionally drawn with the pyrimidine ring on the left. There are relatively few naturally occurring pyr-azines or pyridazines. 

Nucleic acids were discovered in 1868-1869, and the biosynthesis of nucleic acid purines de novo was explicitly proposed by Miescher in 1874. He had observed that Rhine salmon converted much of their tissue mass (i.e., protein) into the nucleic acids of spermatozoa during migration upstream, although they do not eat during this period. In 1885 a tenfold increase in the total purine content of silkworm eggs was observed to occur during development, and similar observations were later made with eggs of other insects and of birds. 

The origins of the ring nitrogens of uric acid were first studied in 1943 by Barnes and Schoenheimer. Little N from urea was incorporated into visceral nucleic acid purines of the rat, and urea could be eliminated as a potential precursor, thereby disproving Weiner s hjrpothesis. N-Ammon-ium citrate was a good precursor of purines, however, and because the specific activity of purines was considerably greater than that of histidine... 

It was also clear that microorganisms living in purine-free environments synthesized their nucleic acid purines de novo via inosinate. 

Hartman, S.C., Buchanan, J.M. Nucleic acids, purines, pyrimidines (nucleotide synthesis). Annu. Rev. Biochem. 28, 365-410 (1959)... 

Abrams and co-workers first showed that the precursors of nucleic acid purines were the same as those of uric acid by demonstrating the incorporation of N -glycine into adenine and guanine of the nucleic acids of growing yeast. Heinrich and Wilson, using the rat, also explored the precursors of purines in nucleic acids, and their results confirmed the earlier observations of Buchanan and collaborators for uric acid. It has now been well substantiated that formate, glycine, and CO2 aU con-... 

AIC has been synthesized with C in position 4 of the imidazole ring and its metabolism studied in animal tissues. It was converted into uric acid by the pigeon, while very little of the label appeared in the respiratory COs. A significant conversion of isotopic AIC into nucleic acid purines and nucleotide purines has been shown when this compound was injected into rats, and similarly into nucleic acid purines in mice. In addition, Williams has shown that it was appreciably converted into the purine compounds of resting and growing yeast. Thus, there is ample evidence that AIC may be converted into a complete purine ring in vivo. 

The corresponding hydroxyl compound, 4-hydroxy-5-imidazole-carboxamide, was also synthesized with and injected into rats. No radioactivity appeared in the respiratory CO2, nucleic acid purines, nucleotide purines, or allantoin. Apparently this substance is not active metabolically in purine synthetic reactions. 

Because of the conflicting results, it seems necessary tentatively to accept the possibility that nucleic acid purines may be synthesized under normal metabolic conditions from preformed purines as well as from elementary precursors. The problem of ascertaining the role in normal metabolism of preformed purine compounds is difficult, since it is known that the mammalian organism is able to synthesize its own purines from simple metabolites and does not require dietary purines. Recent studies indicate that incompleted purine structures joined to ribose and phosphate are intermediates in purine synthetic reactions in vitro, and that... 

Abrams and Goldinger have described an in vitro system consisting of erythroid rabbit bone marrow slices which forms nucleic acid purines from glycine-l-C or from labeled adenine or guanine.They observed a small but definite conversion of adenine to guanine and likewise of... 

Adenine is inert in the nucleoside phosphorylase systems of both mammalian tissues and microorganisms, but isotopically labeled adenine is effectively incorporated into nucleic acid purines, both in rats " and in yeast.This poses a question as to the possible role of nucleoside phosphorylase in polynucleotide synthesis. It has been suggested that hypoxanthine or guanine nucleosides (or nucleotides) are synthesized first. Then an exchange reaction with free adenine (or a derivative) might occur, For example, adenine might react with inosine to form adenosine and hypoxanthine. Some known exchange reactions are discussed below. 

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