Purines from nucleic acids

Table 2. End products of the degradation of purines (from nucleic acids) in animals...

A further unusual feature of the matrix-dependent polycondensation lies in the character of the nucleobases themselves. Purine mononucleotides undergo polycondensation, in good yields, at complementary matrices consisting of pyrimidine polymers. However, the synthesis of pyrimidine oligonucleotides from their mononucleotides at purine matrices is not effective. This important fact means that a pyrimidine-rich matrix leads to a purine-rich nucleic acid, which is itself not suitable to act as a matrix. This phenomenon also occurs when matrices are used which contain both basic species, i.e., purines and pyrimidines. An increase in the amount of purine in a matrix leads to a clear decrease in its effectiveness (Inoue and Orgel, 1983). However, the authors note self-critically that the condensation agent used cannot be considered to be prebiotic in nature. 

Ammonia is generated mainly from the metabolism of amino acids and from the catabolism of purine and pyrimidine bases, which are produced from nucleic acids. Since it is toxic, it must be converted to a non-toxic compound for excretion from the body. This is achieved via the ornithine cycle, more usually known as the urea cycle. 

A. Salvage pathways allow synthesis of nucleotides from free purines or pyrimidines that arise from nucleic acid degradation or dietary sources, which is more economical for the cell than de novo synthesis. 

Dietary purines are not an important source of uric acid. Quantitatively important amounts of purine are formed from amino acids, formate, and carbon dioxide in the body. Those purine ribonucleotides not incorporated into nucleic acids and derived from nucleic acid degradation are converted to xanthine or hypoxanthine and oxidized to uric acid (Figure 36-7). Allopurinol inhibits this last step, resulting in a fall in the plasma urate level and a decrease in the size of the urate pool. The more soluble xanthine and hypoxanthine are increased. 

The term "nucleoside refers to the A -glycosylpurines and jV-glycosylpyrimidines derived from nucleic acids. The common chemical feature of purine nucleosides is a -D-ribofuranosyl or a 2 -deoxy- 8-D-ribofuranosyl moiety linked to N9 of the purine base. Adenosine (1) and guanosine (2) are the most common purine nucleosides of RNA, whereas DNA contains 2 -de-oxyadenosine (3) and 2 -deoxyguanosine (4). 

The existence of inhibitors in various tissues probably explains the discrepancies in the literature regarding the level of DNase in serum. Red blood cells contain a large amount of inhibitor of DNase that is easily released, and it has been postulated that the presence of this inhibitor in serum samples has led to the variations between published analytical results (G18). It is quite natural to speculate on the possible significance of the levels of these nucleic acid-destroying enzymes to the production of purine breakdown products from nucleic acids. 

Uric acid is the end product of purine metabolism in man. Consequently, abnormal levels of uric acid serve to indicate disorders of metabolism of purines or nucleic acids. Serum levels of uric acid range from 200 to 420 pmol/L In males 15 to 20% and 3 to 4% of females suffer from hyperuricaemia. 

II. The Structure of Purine Nucleosides Derived from Nucleic Acids. 302... 

II. The Stbuctubb of Purine Nucleosides Derived FROM Nucleic Acids... 

Since a comprehensive summary of the vast efforts that have been expended in establishing the exact structure of the purine and pyrimidine nucleosides derived from nucleic acids has recently appeared in this Series, the details of this work will be mentioned briefly but will not be discussed here. 

In this chapter we examine the synthesis and degradation of purines, pyrimidines, and hemes. These have complex structures, but are formed from simple precursors. All three can be synthesized in the body and have roles ranging from nucleic acids to hemoglobin. In addition to synthesis control of all three classes of compounds, a number of metabolic diseases associated particularly with purine and heme metabolism are discussed. The use of antimetabolites, as in chemotherapy, and the rationale for their use is presented. 

Some of the substances that have been separated by this method are given in papers referred to by Morris and Morris (1964) amino acids, peptides (particularly those having molecular weights ranging from 500 to 5000), polypeptide antibiotics, proteins (including enzymes), carbohydrates (although for most compounds in this chemical class other fractionation methods are much more frequently applied), purines, pyrimidines, nucleic acid derivatives, tRNA s that are specific for various amino acids, organic acids, steroids, lipids, antibiotics that are not peptides, porphyrins, pterins, vitamin B,2 and other vitamins, lipoic acid, and alkaloids. The countercurrent-distribution procedure of Holley et al. (1965) is widely used, sometimes with modifications. Korte et al. (1965) have separated three isomers of tetrahydrocannabinol. 

As is well known, the two purines, adenine and guanine, originating from nucleic acids or from high-energy phosphate compounds like ATP or GTP, are catabolized in man to uric acid. The intermediately formed hypoxanthine and xanthine are both oxidized to uric acid by the enzyme xanthine oxidase. This enzyme introduces an oxygen atom between the carbon and hydrogen atom in position Cg. Of the two tautomeric forms of uric acid, the amido (lactam) and the imido (lactim) forms, the latter has a more acid character. 

From these results on may conclude that purines in mononucleotides are absorbed to a larger extent than purines in nucleic acids in the case of 5 -AMP this absorption would appear to be nearly quantitative. 

Harber and Maddocks (79) discuss the separation of purine analog from nucleic acid derivatives on ECTEOLA-cellulose TLC and described the isolation of azathioprine, an imidazole derivative of 6-mercaptopurine to which it is con verted in vivo, and 6-MP from a mixture of purines and pyrimidines. 

Purines have a double ring structure with carbon and nitrogen atoms forming a six-molecule ring attached to a five-molecule ring. Nucleosides are formed by the attachment of a five-carbon sugar to a purine. Purines do not come from the diet - they are either synthesized in the liver or recovered from nucleic acids. Purine synthesis only occurs in the cytosol of Hver cells. The breakdown of purines forms uric acid. 

The presence of nucleic acids ia yeast is oae of the maia problems with their use ia human foods. Other animals metabolize uric acid to aHantoia, which is excreted ia the uriae. Purines iagested by humans and some other primates are metabolized to uric acid, which may precipitate out ia tissue to cause gout (37). The daily human diet should contain no more than about 2 g of nucleic acid, which limits yeast iatake to a maximum of 20 g. Thus, the use of higher concentrations of yeast proteia ia human food requires removal of the nucleic acids. Unfortunately, yields of proteia from extracts treated as described are low, and the cost of the proteia may more than double. 

The 8-aza analogs of purine bases were the first to be studied among all the aza analogs of nucleic acid bases (as early as 1945). Before that time the chemistry of these substances had not been treated in detail from any aspect. Thus the entire chemistry of the u-triazolo [4,5-d]pyrimidines was developed only in connection with the study of antimetabolites of nucleic acid components. Therefore all the papers involved are largely of preparative character and only rarely discuss. theoretical points. 

The nucleic acids DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are biological polymers that act as chemical carriers of an organism s genetic information. Enzyme-catalyzed hydrolysis of nucleic acids yields nucleotides, the monomer units from which RNA and DNA are constructed. Further enzyme-catalyzed hydrolysis of the nucleotides yields nucleosides plus phosphate. Nucleosides, in turn, consist of a purine or pyrimidine base linked to Cl of an aldopentose sugar—ribose in RNA and 2-deoxyribose in DNA. The nucleotides are joined by phosphate links between the 5 phosphate of one nucleotide and the 3 hydroxyl on the sugar of another nucleotide. 

This series in heterocychc chemistry is being introduced to collectively make available critically and comprehensively reviewed hterature scattered in various journals as papers and review articles. All sorts of heterocyclic compounds originating from synthesis, natural products, marine products, insects, etc. will be covered. Several heterocyclic compounds play a significant role in maintaining life. Blood constituents hemoglobin and purines, as well as pyrimidines, are constituents of nucleic acid (DNA and RNA). Several amino acids, carbohydrates, vitamins, alkaloids, antibiotics, etc. are also heterocyclic compounds that are essential for life. Heterocyclic compounds are widely used in clinical practice as drugs, but all applications of heterocyclic medicines can not be discussed in detail. In addition to such applications, heterocyclic compounds also find several applications in the plastics industry, in photography as sensitizers and developers, and the in dye industry as dyes, etc. 

Human tissues can synthesize purines and pyrimidines from amphibolic intermediates. Ingested nucleic acids and nucleotides, which therefore are dietarily nonessential, are degraded in the intestinal tract to mononucleotides, which may be absorbed or converted to purine and pyrimidine bases. The purine bases are then oxidized to uric acid, which may be absorbed and excreted in the urine. While little or no dietary purine or pyrimidine is incorporated into tissue nucleic acids, injected compounds are incorporated. The incorporation of injected [ H] thymidine into newly synthesized DNA thus is used to measure the rate of DNA synthesis. 

Ingested nucleic acids are degraded to purines and pyrimidines. New purines and pyrimidines are formed from amphibohc intermediates and thus are dietarily nonessential. 

The anticodon region consists of seven nucleotides, and it recognizes the three-letter codon in mRNA (Figure 38-2). The sequence read from the 3 to 5 direction in that anticodon loop consists of a variable base-modified purine-XYZ-pyrimidine-pyrimidine-5h Note that this direction of reading the anticodon is 3 " to 5 whereas the genetic code in Table 38—1 is read 5 to 3 since the codon and the anticodon loop of the mRNA and tRNA molecules, respectively, are antipar-allel in their complementarity just like all other inter-molecular interactions between nucleic acid strands. 

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