NUCLEIC ACIDS

NUCLEIC ACIDS, compounds consisting of residues of phosphoric acid, purine and pyrimidine bases, and a carbohydrate. They enter as prosthetic (non-protein) groups into the composition of so-called nucleoproteins (see), participating in the construction of the cell nucleus, but apparently can also occur in a free form in the cell protoplasm. Complexes containing one molecule of phosphoric acid, a carbohydrate, and a purine or pyrimidine base are called mononucleotides or simply nucleotides. Nucleic acids, however, which are complexes of several linked residues of mononucleotides, are called polynucleotides. In nature, two groups of nucleic acids are encountered, differing in their origin and in the nature of the components that make up their composition. The prototype of plant nucleic acid can be the nucleic acid obtained from yeast. Animal nucleic acids can be isolated from the most diverse organs and tissues; the most typical is thymonucleic acid from the thyroid gland. Animal nucleic acids of different origins differ from each other in their structure; in animal tissues, nucleic acid is also found that is completely analogous to that found in yeast. The molecule of plant and animal polynucleotides contains adenine and guanine among the purine bases, and in plant nucleic acids, cytosine and uracil among the pyrimidine bases, while in animal nucleic acids, cytosine and thymine. The main difference between animal and plant nucleic acids lies in the nature of the carbohydrate that makes up their composition. Plant nucleic acid contains a pentose, specifically α-ribose. The distribution of this carbohydrate in nature is strictly limited: it has not been found anywhere except in nucleic acids. The nature of the carbohydrate in animal nucleic acid remained controversial for a long time, and only recently Levene established that the carbohydrate with 5 carbon atoms, a derivative of ribose, specifically d-2-deoxyribose (or ribodesose): named by him thymonose. The method of linking individual components in the nucleotide molecule has been clarified. An example can serve as the structural formula of adenine-nucleotide (adenylic acid):

-O-N=C-NH₂ I IHC C-N C-N adenine \ ^CH C-C-C-C-C-O-P ^0 \ ribose-phosphoric acid

According to this structure, with careful hydrolysis in an alkaline medium, complexes of carbohydrate and purine are obtained, the so-called nucleosides, and with hydrolysis in an acidic medium, on the contrary, the purine is cleaved off and a compound of carbohydrate with phosphoric acid remains. The method of linking individual mononucleotides in the nucleic acid molecule is less clear and remains controversial. Possible linkages are: 1) by the type of simple ethers between two carbohydrate residues, 2) by the type of complex esters between the carbohydrate and phosphoric acid, and 3) by the type of anhydrides of phosphoric acid between two residues of the latter. It is very probable that in the nucleic acid molecule linkages of different types are encountered (cf. diagram): Phosphoric acid-pentose-base * Phosphoric acid-pentose-base *_l '------------------------^! Phosphoric acid-pentose-base Phosphoric

acid-pentose-base Phosphoric

acid-pentose-base

acid-pentose-base

I Phosphoric

acid-pentose-base

acid-pentose-base

J (Levene) (Jones) Phosphoric acid-pentose-base Phosphoric acid-pentose-base Phosphoric acid-pentose-base (Feulgen) Phosphoric acid-pentose-base Mononucleotides: guanine-nucleotide (guanylic, or guanosine-phosphoric acid) has been found in the pancreas, where it may enter into the composition of a polynucleotide. Inosinic acid (hypoxanthine-nucleotide, hypoxanthosine or inosine-phosphoric acid), discovered by Liebig in meat, is not preformed in tissues, but is formed from adenylic acid by deamination. Adenylic acid (adenine-nucleotide, adenosine-phosphoric acid) was discovered in the blood by Buel and Perkins, in the muscle by Embden. It is the source of ammonia formation in the blood and in muscles (Ragnas). In the muscle (and possibly in other cells) it apparently plays an important, but not yet clarified role in the general chemical dynamics. Here the nucleic acid is a derivative not of orthophosphoric, but of pyrophosphoric acid (Lohmann). It is possible that here there is a derivative of triphosphoric acid (Embden). According to Lohmann, nucleic acid in the muscle plays the role of a complement necessary for the action of the glycolytic enzyme.-NUCLEOSIDES-complexes of carbohydrate and purine base-are obtained by cleaving off phosphoric acid from nucleotides. They have significance as intermediate products of nucleic exchange in that in this form deamination of aminopurins occurs most easily (see below). Adenosine (adenine-pentose) gives in this case hypoxanthosine (inosine), guanosine gives xanthosine. The biological significance of nucleic acids is determined primarily by their role as the main structural part participating in the construction of the cell nucleus, in particular its chromatin, and consequently also the chromosomes. Nucleic acids are assigned the role of fine regulators of hydrogen ion concentration; this regulation is carried out either by breaking ether bonds with the release of acid groups or by the cleavage of ammonia with a corresponding shift [H*] in the alkaline direction. This may have special importance for maintaining the constancy of the active reaction in the nucleus with its most important biological functions.-The final product of transformations of the characteristic component of nucleic acids-purine bases-in the human organism is uric acid, and the pathology of uric acid metabolism (gout) is to a considerable extent the pathology of nucleic exchange. Enzymes of nucleic exchange. The former term "nucleases," if it can be preserved, should be used not to denote one enzyme, but their aggregate participating in the cleavage of nucleic acids: 1) polynucleotidases (nucleinases)-cleave nucleic acids into individual mononucleotides; 2) nucleotidases-cleave off phosphoric acid from nucleotides with the formation of nucleosides; 3) nucleosidases-complete the cleavage by breaking the glycosidic bond between the purine (pyrimidine) base and the carbohydrate. In the stomach, hydrolysis of the protein part of nucleoproteins occurs with the formation of intermediate, less protein-rich compounds, the so-called nucleins. Complete cleavage and hydrolysis of the protein part is carried out by intestinal proteases; the liberated nucleic acids are cleaved by corresponding enzymes to the stage of nucleosides. Nucleosidases are apparently not present in the intestine; they are typical enzymes of cellular and tissue exchange. In the organism, even before complete cleavage, the products of nucleic acid degradation undergo deamination, leading to the formation of oxypurines; subsequent oxidation leads to uric acid as the final product. Free aminopurines deaminate much more difficult than when they are part of nucleosides and nucleotides. On the other hand, the more oxidized the purine base that is part of the complex, the less stable the latter.

V. Engelhardt. Nucleic acid is a white, non-hygroscopic, amorphous powder, insoluble in alcohol and ether, slightly soluble in cold water, more easily soluble in hot water, and easily soluble in alkaline solutions. 3-5% aqueous solutions of N. k. gel upon cooling into a glue-like jelly. Solutions of N. k. rotate to the right. Most heavy metals and alkaloid reagents give precipitates with N. k. Upon cleavage with hydrochloric or sulfuric acid, phosphoric acid, pentoses, and derivatives of pyrimidine (uracil, cytosine, thymine) or purine bases (adenine, guanine, hypoxanthine, xanthine) are found. Similar cleavage can be effected by enzymes (nucleases). N. k. does not contain sulfur. In medicine, the powder of N. k., obtained from yeast, is used; it is white, grayish-white, or yellowish-white in color, with a very faint yeast odor. It is used almost exclusively in the form of the sodium salt (Natrium nuclecinicum) for subcutaneous administration in non-specific protein therapy. Under the name Schütte, ready-made preparations are sold in France: pills, tablets, and saccharate; they contain, in addition to nucleic acids, the constituent parts of grain. The therapeutic value is due to the supply of phosphorus to the body, contained both in the N. k. itself and in the constituent parts of grain. -Doses: up to 10 pills a day during meals or 8.0 of saccharate also during each meal. The sodium salt of nucleic acid is a fine, slightly yellowish powder, easily soluble in water, especially when heated; it is more frequently used subcutaneously in 2-10% aqueous solution to increase leukocytosis in infectious diseases, in surgery, in psychoses, etc. -Phagocytin (Phagocytin) is a preparation of the sodium salt of N. k., dispensed in ampoules of 1 cm³ of 5% solution of the sodium salt of N. k. In medicine, the following compounds of N. k. are also used. Compound with iron, containing 1 molecule of N. k. to 2 molecules of iron. A brown powder, gradually soluble in water, but easily with a brownish discoloration. Used in anemia and chlorosis internally in 0.5 doses daily as a preparation containing phosphorus and iron. Trade names: Ferrum nucleinicum, Ferrinol, Ferratogen, Nucleogen, etc. The silver salt of N. k. (Argentum nucleinicum) contains 18% silver; a greenish-black powder, easily soluble in water (up to 50%). Used in gonorrhea in 1-2% solutions. Another silver nucleic preparation, nargol (Nargol), contains 10% silver, is a light brownish-yellow powder, easily soluble in water. Mercury compounds of N. k. - Levurargyr, Mercedan, Mercurol (see Mercury). In these preparations, as well as in the aforementioned silver salt, nucleic acid does not play an active therapeutic role, serving only to obtain water-soluble compounds with Ag or Hg. The same is the significance of N. k. in the preparations Chininum nucleinicum, Cuprum nucleinicum, Nucleohexyl (compound of N. k. with hexamethylenetetramine), etc. N. Kornilov.