Adenine incorporation into tissue nucleic acids

It is also possible that the high xanthine oxidase activity of rat tissues was responsible for the nonutilization of hypoxanthine, since the base was extensively converted to allantoin (800). However, it is well known that hypoxanthine, as well as other purines, were also substrates for an anabolic enzyme system in the rat, namely, nucleoside phosphorylase (816). Hypoxanthine was readily utilized for the synthesis of both adenine and guanine of RNA and DNA in slices of rabbit bone marrow (808a), even though it was not incorporated into the nucleic acids of the rat (800). Bone marrow may lack xanthine oxidase, thus leaving hypoxanthine available to participate in synthetic reactions. Thus, the competition of several enzyme systems for the administered compound may have determined its final disposition. 

Many animal tissues synthesized nucleic acids de novo from elementary precursors as well as from preformed purines in the diet. Other tissues, such as bone marrow, had a limited capacity for purine synthesis by the de novo route and appeared to utilize preformed purine compounds that were manufactured in the liver (450). In this experiment, the amount of formate-C incorporated into the bases of DNA of marrow cells was measured in control and hepatectomized rabbits. In control animals, the ratio of the specific activity of thymine to adenine was approximately 1, indicating a similar degree of incorporation of formate-C into the purine ureide carbons and into the thymine methyl group of DNA in bone marrow cells in vivo. In hepatectomized rabbits, the total incorporation of formate-C was substantially depressed but the thymine adenine ratio was increased to 27. The conclusion that the liver supplied preformed purines to the marrow cells was supported by the earlier observation that marrow cells in vitro utilized preformed adenine quite efficiently for nucleic acid synthesis (451). 

Lu KH, Winnick T. Studies of nucleic acid metabolism in embryonic tissue culture with the aid of C -labeled purines. Exp Cell Res 6 345-352, 1954. See also Lajtha CP, Oliver R, Ellis, F. Incorporation of P and adenine- C into DNA by human bone marrow cells in... 

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. 

Fortunately, my graduate research in biochemistry at Baylor College of Medicine, in Houston, involved studies on the mechanism of formic acid oxidation in animal tissues and on the incorporation of this one-carbon compound into nucleic acid components and their precursors. This provided me with experience in the use of isotopic tracers and the background in biochemical research which proved crucial, in later years, for unraveUng the intermediates and mechanisms of synthesis of purines and other compounds, when I discovered the prebiotic synthesis of adenine and other building blocks of nucleic acids, and a general pathway or method for the prebiotic formation of oligodeoxynucleotides and peptides. 

In a short while, it was established that the precursors of nucleic acid purines were the same as those of uric acid. N -glycine was incorporated into adenine and guanine of the nucleic acids of growing yeast 28), and the earlier observations for uric acid precursors in the pigeon were confirmed for the nucleic acids of the rat 24). It has been substantiated in a variety of tissues that formate, glycine, and CO2 all contributed in major proportions to the synthesis of allantoin 25) and nucleic acid adenine and guanine... 

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