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.
Goode
D
D
Wolfson Laboratory, School of Animal and Microbial Sciences, The University of Reading, Whiteknights, UK.
Lewis
M E
ME
Crabbe
M J
MJ
D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism; D002417:Cattle; D005947:Glucose / Q000378:metabolism*; D005965:Glucuronates / Q000378:metabolism*; D020723:Glucuronic Acid; D014453:Glucuronosyltransferase / Q000378:metabolism; D007700:Kinetics; D007908:Lens, Crystalline / Q000378:metabolism*; D008322:Mammals; D008954:Models, Biological; D051381:Rats; D013401:Sugar Alcohol Dehydrogenases / Q000378:metabolism; D014993:Xylitol / Q000378:metabolism*
D005965:Glucuronates; D020723:Glucuronic Acid; D002237:Carbohydrate Dehydrogenases; D013401:Sugar Alcohol Dehydrogenases; C023300:L-xylulose reductase; C020590:L-glucuronate reductase; C020843:gulonate dehydrogenase; D014453:Glucuronosyltransferase; D005947:Glucose; D014993:Xylitol