FOLATE METABOLISM IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Metabolic changes in folic acid and their polyglutamyl derivatives wer e studied in streptozotocin-induced diabetic rats. Polyglutamylfolates , which constituted about 70% of the folates (determined by the Lactob acillus casei microbiological assay) in normal rat liver, were observe d to be hydrolyzed to a greater extent to simple monoglutamyl forms as the diabetes progressed. Only 4-5% conjugated folates were observed 2 5 days after the injection of streptozotocin. Total methylfolates, whi ch represented 70-75% of total folates, were lowered by 60% and methyl polyglutamylfolates by 95% in the diabetic rat. An imbalance in the tw o folate-metabolizing enzymes, folyl conjugase and folylpolyglutamate synthetase, were observed in diabetes, the former being 2-3-fold highe r and the latter being 7-8-fold lower. [C-14]Folate uptake studies ind icated that folates accumulated for up to the first 24 h in diabetic r at liver, and then were depleted over the next 48 h period, indicating an impaired polyglutamylation and storage of folates.