UV filter compounds in human lenses: the origin of 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-beta-D-glucoside.
OBJECTIVE
To investigate UV filter synthesis in the human lens, in particular 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 chromatography (HPLC) after separate incubation with 3H-tryptophan (3H-Trp), beta-benzoylacrylic acid, D,L-alpha-amino-beta-benzoylpropionic acid, or D,L-3-hydroxykynurenine 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 postnatal lens displaying measurable levels of UV filters. In adults no radiolabel was incorporated into 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-beta-D-glucoside after 3H-Trp incubations. Beta-benzoylacrylic acid was readily 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-hydroxyphenyl)-4-oxobutanoic acid O-beta-D-glucoside, respectively, after lens incubations.


CONCLUSIONS
UV filter biosynthesis appears to be activated at or near birth. Compounds containing the kynurenine side chain slowly deaminate, and in the lens, the newly formed double bond is rapidly reduced. These findings suggest that 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-beta-D-glucoside is derived from L-3-hydroxykynurenine O-beta-D-glucoside through this deamination-reduction process. The slowness of the deamination presumably accounts for the absence of incorporation of radiolabel from 3H-Trp into 4(2-amino-3-hydroxyphenyl)4-oxobutanoic acid O-beta-D-glucoside.
Bova
L M
LM
Australian Cataract Research Foundation, Department of Chemistry, University of Wollongong, New South Wales.
Wood
A M
AM
Jamie
J F
JF
Truscott
R J
RJ
D000179:Acrylates / Q000378:metabolism; D000328:Adult; D000375:Aging / Q000502:physiology; D001565:Benzoates / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003641:Deamination; D005333:Fetus; D005960:Glucosides / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism*; D008875:Middle Aged; D010654:Phenylbutyrates / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism; D014466:Ultraviolet Rays
D000179:Acrylates; D001565:Benzoates; D005960:Glucosides; D010654:Phenylbutyrates; D011422:Propionates; C400970:amino-beta-benzoylpropionic acid; C400967:benzoylacrylic acid; C400972:benzoylpropionic acid; C088377:4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-glucoside; C005045:3-hydroxykynurenine; D007737:Kynurenine; D014364:Tryptophan