Amino acids radical damage

Organic free radicals are key intermediates in a number of reactions of biological significance. For istance, there is strong evidence that the biosynthesis of several natural substances and many enzymatic reactions involve amino acid radicals[126-129], and radiation damage to DNA is known to proceed through a number of base-centered radicals[130-132]. Furthermore organic free radicals can be exploited as spin probes in the study of macromolecular systems by means of EPR spectroscopy [133]. 

Studies in radiation biochemistry have shown that there is some localization of free radical damage to enzymes and proteins at their sulfur amino acids. In proteins irradiated in solution cysteine, cystine and methionine arc some of the most labile amino acids. Radiation in the dry state allows electron spin resonance measurements and Gordy (1958) has shown the localization of unpaired electrons at sulfur in amino acids and proteins. As described previously in this article, in the damage to cytochrome c by linolenate peroxidation, cystine and methionine are among the most labile amino acids. If damage is localized at a sulfhydryl site on a protein, immediate molecular repair is possible by a sulfur interchange of the unpaired electron,... 

Griffiths, H.R, Lunec, J. and Blake, D.R. (1992). Oxygen radical-induced fluorescence in proteins identification of the fluorescent tryptophan metabolite N formyl kynurenine as a biological index of radical damage. Amino Acids 3, 183-194. 

The modification of amino acids in proteins and peptides by oxidative processes plays a major role in the development of disease and in aging (Halliwell and Gutteridge, 1989, 1990 Kim et al., 1985 Tabor and Richardson, 1987 Stadtman, 1992). Tissue damage through free radical oxidation is known to cause various cancers, neurological degenerative conditions, pulmonary problems, inflammation, cardiovascular disease, and a host of other problems. Oxidation of protein structures can alter activity, inhibit normal protein interactions, modify amino acid side chains, cleave peptide bonds, and even cause crosslinks to form between proteins. 

There are at least two answers to question (i). First, abnormal proteins can arise in cells due to spontaneous denaturation, errors in protein synthesis, errors in post-translational processing, failure of the correct folding of the protein or damage by free radicals. They are then degraded and replaced by newly synthesised proteins. Secondly, turnover helps to maintain concentrations of free amino acids both within cells and in the blood. This is important to satisfy the requirements for synthesis of essential proteins and peptides (e.g. hormones) and some small nitrogen-containing compounds that play key roles in metabolism (see Table 8.4). 

In a study of intermediate duration, dermal application of 0.5% p-cresol for 6 weeks produced permanent depigmentation of the skin and hair of mice (Shelley 1974). A caustic effect on the skin was noted in one strain of mouse, but not another. Neither o- nor m-cresol produced any color change in the mice. The author suggests that only p-cresol is active because it mimics the structure of tyrosine, the amino acid present in melanin, so that tyrosinase acts on it, liberating free radicals that damage melanocytes. NOAEL and LOAEL values were not derived from this study because the applied dose was not reported. 

TEARS is not restricted to lipids, as other substrates are capable of producing MDA and react with TBA. For example, amino acids, carbohydrates and DNA are damaged by free radicals in the presence of Fe(III) ions, leading to products that ultimately release MDA" . ... 

As noted, vitamin C is needed for the production of collagen in the body, but it is also essential in the production of certain hormones such as dopamine and adrenaline. Ascorbic acid is also essential in the metabolism of some amino acids. It helps protect cells from free radical damage, helps iron absorption, and is essential for many metabolic processes. The dietary need of vitamin C is not clearly established, but the U.S. National Academy of Science has established a recommended dietary allowance (RDA) of 60 mg per day. Some groups and individuals, notably Linus Pauling in the 1980s, recommend dosages as high as... 

This mechanism is of importance in radical induced amino acid damage catalyzed by copper ions. The study of the decomposition of transients with a metal-carbon -bond containing two potential leaving groups (both an amine and a carboxylate group) at the p position of the carbon centered radical is of special interest. It was reported that the intermediate formed with the amino acid 2-methylalanine with cupric ions decomposes via p-carboxyl elimination whereas the intermediate formed with cuprous ions decomposes via p-amine elimination (102). 

Bielski BFIJ, Shiue GG (1979) Reaction rates of superoxide radicals with the essential amino acids. In Oxygen free radicals and tissue damage. Ciba Foundation Symposium 65, Amsterdam, pp 43-56... 

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