Cysteine is the initial site of modification of alpha-crystallin by kynurenine

Tryptophan metabolites, such as kynurenine, are spontaneously unstable at n eutral pH. They undergo side-chain deamination yielding reactive alpha, bet a unsaturated ketones, In the lens, where these compounds act as UV filters , reaction of the breakdown products with lens proteins (crystallins) may b e largely responsible for age-dependent colouration of this tissue. In prev ious research, where high pH (pH 9) was used to promote deamination and con jugation with lens protein, histidine, lysine, and cysteine residues were f ound to be modified. In this study we show that, at pH 7, site of reaction with the major lens chaperone alpha-crystallin, is the single cysteine resi due of the alpha A subunit, This apparent selectivity has important ramific ations because the cysteine-kynurenine adduct is itself unstable under phys iological conditions. (C) 2000 Academic Press.