Lens proteins oxidation

The findings discussed above suggest that the presence of Met(O) residues in a-l-PI and lens proteins might account for some of the observed clinical manifestations. It is of interest to speculate that Met(0)-peptide reductase may function as a repair enzyme to prevent the accumulation of Met(O) residues in most proteins. Whether in those examples as discussed above, the accumulation of Met(O) in proteins is a result of an overwhelming increase in the synthesis of biological oxidants and/or a decrease in the ability to either destroy the biological oxidants or reduce the Met(O) residues in the proteins is not known. If it is the latter, this could be due to a decrease in the reductase itself or to some impairment in the reducing system that the enzyme requires. 

In addition to a-l-PI, there are other examples of the presence of Met(O) residues in proteins isolated from biological material. Proteins found in lens tissue are particularly susceptible to photooxidation and because of the long half-lives of these proteins, any oxidation could be especially detrimental. In this tissue, protein synthesis is localized to the outer region of the tissue and most proteins are stable for the life of the tissue - ". It is thus somewhat surprising that not only is there no Met(O) residues in the young normal human lens but even in the old normal human lens only a small amount of Met(O) residues is found . However, in the cataractous lens as much as 65% of the Met residues of the lens proteins are found in the form of Met(0) . Whether this increase in Met(O) content in these proteins is a cause or a result of the cataracts is not known. In order to determine whether the high content of Met(O) in the cataractous lens is related to a decreased activity of Met(0)-peptide reductase, the level of this enzyme was determined in normal and cataractous lenses. It can be seen from Table 9 that there are no significant differences between the levels of Met(0)-peptide reductase in normal and cataractous lenses. In spite of these results, however, it is still possible that the Met(0)-peptide... 

Incubation of D-xylose with an aqueous solution of bovine lens protein gave both xylitol and xylonic acid. Studies of the reaction under a variety of conditions suggest that both the reduction and oxidation reactions are protein (possibly enzyme) catalyzed and appear to be unique to lens... 

M. C. Wells-Knecht, T. G. Huggins, D. G. Dyer, S. R. Thorpe, and J. W. Baynes, Oxidized amino acids in lens protein with age. Measurement of o-tyrosine and dityrosine in the aging human lens, J. Biol. Chem., 1993, 268, 12348-12352. 

D25. Dunn, J. A., Patrick, J. S., Thorpe, S. R., and Baynes, J. W., Oxidation of glycated proteins Age-dependent accumulation of N epsilon-(carboxymethyl)lysine in lens proteins. Biochemistry 28, 9464-9468 (1989). 

Roberts, J.E. and Dillon, J. (1987) In vitro studies on the photosensitized oxidation of lens proteins by porphyrins, Photochem. Photobiol., 46, 683-688. 

Roberts J.E., Finley, E.L., Patat, S.A., and Schey, K.L. (2001) Photo-oxidation of lens proteins with xanthurenic acid a putative chromophore for cataractogenesis, Photochem. Photobiol., 74, 740-744. 

Further experiments showed that GSH is capable of preventing oxidative coupling between (auto)oxidised HK and lens proteins [116]. This observation, taken together with the known decrease of GSH concentration within lens with age [136-137 ], leads to the reasonable conclusion that GSH may prevent lens damage by HK and/or (auto)oxidised derivatives. The mode of GSH action is mainly an adverse effect on HK (auto)oxidation, also confirmed by the increased rate of GSH oxidation in the presence of autoxidising HK. 

Dische, Z. and Zil, H. (1951) Studies on the oxidation of cysteine to cystine in lens proteins during cataract formation. Am. J. Ophthalmol, 34, 104-13. 

Slight, S. H., Feather, M. S., and Ortwerth, B. J., 1990, Glycation of lens proteins by the oxidation products of ascorbic acid, Biochim. Biophys. Acta 1038 367-374. 

Hunt, J. V., Jiang, Z. Y., and Wolff, S. P., 1992b, Formation of hydrogen peroxide by lens proteins Protein-derived hydrogen peroxide as a potential mechanism of oxidative insult to the lens. Free Rad. Biol. Med. 13 319-323. 

Glutathione and Protein Oxidation and Precipitation in the Process of Aging and Cataract Formation in the Lens... 

---