GLUCURONIC ACID PATHWAY IN ALLOXAN DIABETIC RABBITS : (I) URINARY EXCRETION OF METABOLITES RELATED TO THE GLUCURONIC ACID PATHWAY

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Studies on the activity of the glucuronic acid pathway in alloxan diabetic rabbits were carried out. Amount of D-glucaric acid, L-ascorbic acid, and D-glucuronic acid in urine increased in the case of the alloxan diabetic rabbits. The transformation from D-glucuronolactone to D-glucaric acid was higher than normal in the diabetic animals. The expired 14CO2 decreased and urinary excretion of labeled L-gulonic acid increased after administration of 6-14C-glucuronolactone in the diabetic rabbits. L-Gulonic acid dehydrogenase, lactonase II, and β-glucuronidase activities were reduced, and UDPGA-pyrophosphatase, D-glucuronic acid-1-phosphatase, and UDPGA-transferase activities increased in the diabetic rabbit liver. From these results, it may be concluded that an increase of endogenous D-glucuronic acid in the diabetic states could be attributed to a metabolic defect in the step of L-gulonic acid dehydrogenation and to the enhancement of UDPGA-pyrophosphatase and D-glucuronic acid-l-phosphate phosphatase activities.
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