The modification of proteins by 3-hydroxykynurenine.
The autoxidation and reactivity towards proteins of 3-hydroxykynurenine, a tryptophan metabolite found in the human lens, has been studied. At neutral pH, 3-hydroxykynurenine was readily oxidized using molecular oxygen with the formation of several coloured products. The autoxidation of both 3-hydroxykynurenine and the related aminophenol, 3-hydroxyanthranilic acid, was inhibited by the inclusion of sulphydryl compounds such as glutathione or cysteine. Covalent adducts involving the thiols were not observed with either aminophenol. 3-Hydroxykynurenine was found to react with proteins, including lens proteins, to produce brown-coloured polypeptides characterized by an indistinct long wavelength absorption. This protein tanning was inhibited by glutathione. Despite the presence of an amino group in the side chain of 3-hydroxykynurenine, this tanning of proteins was found to involve amino groups including those of lysine residues, as has been found for 3-hydroxyanthranilic acid. Although both aminophenols tanned polylysine, only 3-hydroxykynurenine induced precipitation of the polyamino acid. 3-Hydroxykynurenine tanned all of the purified crystallins but induced precipitation only in the case of alpha A-crystallin. The implications of these findings for senile cataract are discussed.
Stutchbury
G M
GM
Australian Cataract Research Foundation, University of Wollongong, NSW.
Truscott
R J
RJ
D015095:3-Hydroxyanthranilic Acid / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D003459:Crystallins / Q000187:drug effects*; D003545:Cysteine / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010084:Oxidation-Reduction; D011107:Polylysine / Q000187:drug effects; D013053:Spectrophotometry; D013997:Time Factors
D003459:Crystallins; D015095:3-Hydroxyanthranilic Acid; D011107:Polylysine; C005045:3-hydroxykynurenine; D007737:Kynurenine; D005978:Glutathione; D003545:Cysteine