3346 Xanthurenic acid involved in formation of fluorescent crystallins aggregates in human lenses

m It has been previously reported that lens fluorescence increases with age and is due to s fluorogeo tightly bound to lens proteins. In this study, we iind that xsathureaic acid axcumulates with age in human eye. Its derivatives, repotted by us ss OX4 and DOXA, formes fluorescent conjugates with the crysttdlins leading IO their aggregation. &&&I& Absorption spectrometry and flue-ce spectrometry were used to characterizize the xsathureuic acid derivatives. Sephsdex G-25 wss used for isolation of conjugates of DOXA with crystsilins. Thin layer chromatogmphy sad HPLC sttslysir were used for DOXA detection in cataractous leases. &g& Xauthureoic acid, the product of eaaymstic 3-hydroxykyaureuine deaminstiou, accumulates in human lenses with sgehtg. At physiological pH, xauthurettic acid forums the tluoresceut aggregstes with u-sad g-crystsllins. The reaction with proteins wss possible due to the trsnsfotmation of xsuthureaic acid into a teutomeric form reported ss OXA. OXA is.oxidized to a quittone, DOXA. OXA sad DOXA rue highly fluorescent. DOXA is about 4M)O-times more fluorescent than 3-hydroxykynurettine with so excitation/emission at 342/453 ttm. (Lsad gctystsiiins after incubation with DOXA become fluorescent with so excitation/emission 341444 ttm. DOXA wss detected in cstsractous human lerws by thin layer chromatography and HPLC analysis. In presence of DOXA, a-crystalho lost its chaperone activity for p-crystsilin. ~nc~siorrs Desmination of 3-hydroxykyttureuine in human leases leads to production of xsttthureuic acid. This substaace is not liuther met&l&d but is transformed to fluoresceut formes, OXA sod DOXA which react with crystsllbts. Xauthurettic acid sccumulstion in the human lenses appears to be so initiating event in senile cataract fonustion. METABOLISM OF POLYCYCLIC AROMATIC HYDROCARBONS IN BOVINE LENS