Free reaction with nucleic acid

Types of Free Radicals and their Reactions with Nucleic Acids... 

The perchlorates of various secondary amines, such as diphenylamine and indole derivatives, are colorless.64 The similarity of colors produced in the presence of hydrochloric acid also attests to the non-auxochromic character of the perchlorate ion in the production of the colored derivative. Consequently, the only role attributable to the perchloric acid in this test is that with nucleic acids it leads to more effective hydrolysis and releases more 2-desoxyribose for reaction with tryptophan. This reaction leads to the production of a substance of the type represented by XV and XVI (R " = H), and the increase in the number of conjugated double bonds results in the product being colored. With ribose, which has a free hydroxyl group at carbon atom 2, a ketone of the type shown in XVII can be formed, and in this case the net result is no increase in the number of double bonds conjugated with the indole nucleus and no comparable increase in color. Hence the test will distinguish between ribose and 2-desoxyribose. 

When oxides of nitrogen come in contact with water, both nitrous and nitric acids are formed (18) (Table IV). Toxic reactions may result from pH decrease. Other toxic reactions may be a consequence of deamination reactions with amino acids and nucleic acid bases. Another consideration is the reactions of oxides of nitrogen with double bonds (Table IV). The cis-trans isomerization of oleic acid exposed to nitrous acid has been reported (19). Furthermore, the reaction of nitrogen dioxide with unsaturated compounds has resulted in the formation of both transient and stable free radical products (20, 21) (Table V). A further possibility has been raised in that nitrite can react with secondary amines to form nitrosamines which have carcinogenic properties (22). Thus, the possible modes of toxicity for oxides of nitrogen are numerous and are not exhausted by this short list. 

Copper is an essential trace element. It is required in the diet because it is the metal cofactor for a variety of enzymes (see Table 50—5). Copper accepts and donates electrons and is involved in reactions involving dismu-tation, hydroxylation, and oxygenation. However, excess copper can cause problems because it can oxidize proteins and hpids, bind to nucleic acids, and enhance the production of free radicals. It is thus important to have mechanisms that will maintain the amount of copper in the body within normal hmits. The body of the normal adult contains about 100 mg of copper, located mostly in bone, liver, kidney, and muscle. The daily intake of copper is about 2—A mg, with about 50% being absorbed in the stomach and upper small intestine and the remainder excreted in the feces. Copper is carried to the liver bound to albumin, taken up by liver cells, and part of it is excreted in the bile. Copper also leaves the liver attached to ceruloplasmin, which is synthesized in that organ. 

The permeability coefficient of 2.6x 10 locm/s at 296 K measured by Deamer is sufficient to supply the enzyme in the liposomes with ADP. How could it be shown that RNA formation actually does take place in the vesicles The increase in the RNA synthesis was detected by observing the fluorescence inside the vesicles. In the interior of the liposomes, the reaction rate is only about 20% of that found for the free enzyme, which shows that the liposome envelope does limit the efficiency of the process. The fluorescence measurements were carried out with the help of ethidium bromide, a fluorescence dye often used in nucleic acid chemistry. 

Guanine is the most easily oxidizable natural nucleic acid base [8] and many oxidants can selectively oxidize guanine in DNA [95]. Here, we focus on the site-selective oxidation of guanine by the carbonate radical anion, COs , one of the important emerging free radicals in biological systems [96]. The mechanism of COs generation in vivo can involve one-electron oxidation of HCOs at the active site of copper-zinc superoxide dismutase [97, 98], and homolysis of the nitrosoperoxycarbonate anion (0N00C02 ) formed by the reaction of peroxynitrite with carbon dioxide [99-102]. 

Just as orotic acid is converted to a ribonucleotide in step e of Fig. 25-14, other free pyrimidine and purine bases can react with PRPP to give monoribonucleotides plus PP . The reversible reactions, which are catalyzed by phosphoribosyltransferases (ribonucleotide pyrophosphorylases), are important components of the salvage pathways by which purine and pyrimidine bases freed by the degradation of nucleic acids are recycled.273 However, thymine is usually not reused. Thymine will react with deoxribose 1-P to form thymidine plus inorganic phosphate (thymidine phosphorylase), and thymidine is rapidly... 

The rate constant for reaction of the electron with biological polymers such as nucleic acids (11) and proteins (7) have been examined. When calculated on a per mole basis the rate constants can be quite high— e.g., ribonuclease (pH 6.8) k = 1.3 X 1010 M l sec.-1, lysozyme (pH 6.2) k = 7.5 X 1010 M l sec.""1), but they are much less than if the constituent units were in free solution. For ribonuclease an attempt has been made to estimate the rate constant from the rate constants for the constituent units (6). Allowance was made for the decrease in collision radius in going from the constituent units to the protein, and for the number of positive charges on the protein molecule. The estimated value agreed with the measured value to within a factor of two or three. If this approach is accepted, one can conclude that the strongest contribution to the reactivity arises from —SS groups, and this conclusion is in line with other evidence from radiation chemistry. 

---