| pubmed-article:12137762 | pubmed:abstractText | Human lenses appear to become coloured with age primarily due to the covalent binding of UV filter compounds to lens proteins. These crystallin modifications result from the inherent instability of the kynurenine UV filters. Here we investigate this decomposition, the role this may have in the formation of other primate UV filters, and the interaction of the intermediates (alpha,beta-ketoalkenes) with lens components. The UV filters kynurenine, 3-hydroxykynurenine and 3-hydroxykynurenine glucoside were incubated at neutral pH in the presence or absence of NADH or NADPH. The three UV filters underwent spontaneous deamination, such that at pH 7 less than half of the starting materials (kynurenine (42%), 3-hydroxykynurenine glucoside (30%) and 3-hydroxykynurenine (21%)) remained after 7 days. In the presence of NAD(P)H, the double bond of the UV filter-derived deamination compounds, were reduced. Deamination of 3-hydroxykynurenine glucoside, followed by reduction with NAD(P)H, could thus account for the formation of the major lens UV filter 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid glucoside. beta-Benzoylacrylic acid, which possesses the same alpha,beta-ketoalkene sidechain as the deaminated kynurenine UV filters, underwent Michael addition with glutathione, was reduced (hydrogenated) by NAD(P)H, however was unreactive with ascorbate. Surprisingly, at pH 7 the UV filter-derived alpha,beta-ketoalkene intermediates, do not readily undergo intramolecular cyclization. This feature makes the double bond more available for reaction with protein nucleophilic residues and other lens components such as glutathione. On the basis of these data it is likely that glutathione and NAD(P)H, but not ascorbate, protect proteins in the lens from modification by UV filters. | lld:pubmed |
