The Hepatic Glucuronate Pathway in the Rat after Treatment with 3,3′,5‐Triiodothyronine and Phenobarbital

The hepatic D-glucuronic acid pathway was studied in male rats after administration of 3, 3′, 5-triidothyronine (20 μg intraperitoneally daily, for three weeks). Some of the key enzymes of the pathway showed decreased activities during hyperthyroidism. D-glucuronolactone dehydrogenase, UDPglucuronosyltransferase and UDPglucuronic acid pyrophosphatase were not affected, whilst the activity of β-glucuronidase was significantly increased. D-Glucaric acid excretion in urine was enhanced and that of L-ascorbic acid was decreased. Phenobarbital administered to hyperthyroid and euthyroid animals (80 mg/kg intraperitoneally, daily, for 3 days) did not markedly affect the differences in the enzyme activities between the two groups. UDP-Glucuronosyltransferase and D-glucuronolactone dehydrogenase activities were induced, and in the case of UDPglucuronosyltransferase the induction was more pronounced during hyperthyroidism. D-Glucaric acid excretion in the urine was increased by phenobarbital treatment both in hyperthyroid and normal animals. L-Ascorbic acid excretion was also increased, but the increase was greater in euthyroid than in hyperthyroid animals. The results suggest that hyperthyroidism favours the metabolism of free D-glucuronic acid towards the formation of D-glucaric acid. Treatment with phenobarbital, however, also enhances to some extent the biosynthesis of L-ascorbic acid.