Hydroxyl radical reaction with nucleic acids

Reactions of Hydroxyl and Hydroxyl-Like Radicals Produced by the Fenton Reaction with Nucleic Acids... 

Salomon J, Elad D (1973) Photochemical reactions of nucleic acid constituents. Peroxide-initiated reactions of purines with alcohols. J Org Chem 38 3420-3421 Salomon J, Elad D (1974) Ultraviolet and y-ray-induced reactions of nucleic acid constituents. Reactions of purines with amines. Photochem Photobiol 19 21-27 Samuni A, Neta P (1973) Hydroxyl radical reaction with phosphate esters and the mechanism of phosphate cleavage. J Phys Chem 77 2425-2429... 

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. 

Several powerful oxidants are produced during the course of metabolism, in both blood cells and most other cells of the body. These include superoxide (02 ), hydrogen peroxide (H2O2), peroxyl radicals (ROO ), and hydroxyl radicals (OH ). The last is a particularly reactive molecule and can react with proteins, nucleic acids, lipids, and other molecules to alter their structure and produce tissue damage. The reactions listed in Table 52-4 play an important role in forming these oxidants and in disposing of them each of these reactions will now be considered in turn. 

King, P. A., Anderson, V. E., Edwards, J. O., Gustafson, G., Plumb, R. C., and Suggs, J. W. (1992). A stable solid that generates hydroxyl radical on dissolution in aqueous solutions Reaction with proteins and nucleic acid. J. Am, Chem. Soc. 114, 5430-5432. 

Peroxynitrite is a nonspecific oxidant that reacts with all classes of biomolecules depleting low-molecular-weight antioxidants, initiating lipid peroxidation, damaging nucleic acids and proteins. Its reactions are much slower than those of the hydroxyl radical but are faster than those of hydrogen peroxide. Comparison of peroxynitrite reactivity with various amino acid residues of human serum albumin have shown that cysteine, methionine, and tryptophan are the most reactive... 

Vittimin E functions as a lipid antioxidemt both in vitro emd in vivo a number of synthetic tmtioxidants will prevent or cure most of the signs of vitamin E deficiency in experimenttil animeds. Polyunsaturated fatty acids undergo oxidative attack by hydroxyl radicals and superoxide to yield tdkylperoxyl (cdkyl-dioxyl) radicals, which perpetuate a chtun reaction in the Upid - with potentiedly disastrous consequences for cells. Similar oxidative radictd damage cem occur to proteins (especially in a lipid environment) and nucleic acids. 

The C-centered radicals of nucleic acid bases generated via hydrogen atom abstraction and addition of hydroxyl or other oxyl radicals to the double bonds also decay rapidly via bimolecular reactions with molecular oxygen. For instance, the rate constant for the reaction of 02 with the C-centered 5-(2 -deoxyuridinyl) methyl radical (U- CH2) derived by hydrogen atom abstraction from the methyl group of thymidine was estimated as 2.2 x 109 M 1 s 1 [61]. The radicals produced by the addition of OH radicals to the C8 position of dG (8-1 IO-dC) also rapidly... 

King PA. A stable solid that generates hydroxyl radical dissolutions in aqueous solutions Reaction with proteins and nucleic acid. J Am Chem Soc 1992 114 5430-4. 

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