UV filter compounds in human lenses: the origin of 4-(2-amino-3-hydroxyphenyl)-4-oxobutanol acid O-beta-D-glucoside

PURPOSE. TO investigate UV filter synthesis in the human lens, in particula r the biosynthetic origin of the second most abundant UV filter compound, 4 -(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-beta-D-glucoside. METHODS. Human lenses were analyzed by high-performance liquid chromatograp hy (HPLC) after separate incubation with H-3-tryptophan (H-3-Trp), beta-ben zoylacrylic acid, D,L-alpha-amino-beta-benzoylpropionic acid, or D,L-3-hydr oxykynurenine O-beta-D-glucoside. The effect of pH on the model compound D, L-alpha-amino-beta-benzoylpropionic acid and D,L-3-hydroxykynurenine O-beta -D-glucoside was also investigated. RESULTS. UV filters were not detected in fetal lenses, despite a 5-month po stnatal lens displaying measurable levels of UV filters, In adults no radio label was incorporated into 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-beta-D-glucoside after 3H-Trp incubations. beta-Benzoylacrylic acid was r eadily reduced in lenses, D,L-alpha-Amino-beta-benzoylpropionic acid and D, L-3-hydroxykynurenine O-beta-D-glucoside slowly deaminated at physiological pH and were converted to beta-benzoylpropionic acid and 4-(2-amino-3-hydro xyphenyl)-4-oxobutanoic acid O-beta-D-glucoside, respectively, after lens i ncubations. CONCLUSIONS. UV filter biosynthesis appears to be activated at or near birt h. Compounds containing the kynurenine side chain slowly deaminate, and in the lens, the newly formed double bond is rapidly reduced. These findings s uggest that 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-beta-D-glucosi de is derived from L-3-hydroxykynurenine O-beta-D-glucoside through this de amination-reduction process. The slowness of the deamination presumably acc ounts for the absence of incorporation of radiolabel from H-3-Trp into 4-(2 -amino-3-hydroxylphenyl)-4-oxobutanoic acid O-beta-D-glucoside.