Accumulation of xylitol in the mammalian lens is related to glucuronate metabolism.

Cataract remains the major cause of blindness worldwide and a common complication of diabetes. Polyol accumulation in the lens is associated with cataract formation. Here we present evidence for a novel pathway for xylitol production in the lens involving glucuronate metabolism. Xylitol can be produced in rat and bovine lens from glucose, via the enzymes myo-inositol-oxygen oxidoreductase, D-glucuronate reductase, L-gulonate NAD(+)-3-oxidoreductase and L-iditol-NAD(+)-5-oxidoreductase, which have been found in the mammalian lens for the first time. Glucuronate reductase has been purified and was inhibited by thiol quenching reagents. UDP-glucuronyl transferase is also present in mammalian lenses; this enzyme may be an anti-toxic defense mechanism in the lens.