The metabolism of (2-14C) + (3',5',7,9-3H) folic acid was studied in normal rats, tumour-bearing rats and rats treated with methotrexate (MTX). The experiments were designed to investigate changes in the catabolism and folate. The breakdown of folate to scission products was again demonstrated to be a normal phenomenon. Catabolites excreted included p-acetamidobenzoate, p-acetamidobenzoyl-L-glutamate, 3H2O, urea and a number of pterins. The catabolic process was decreased in the presence of a tumour and increased by the administration of MTX. MTX also led to the excretion of 4 additional radioactive pterins not found in normal urine. The possible mechanisms of folate breakdown are discussed with reference to the point of action of MTX.
The metabolism of [2-14C]+[3', 5', 7, 9-3H] folic acid and [214C]+[3', 5', 7, 9-3H] 10-formylfolate was studied in hospital inpatients. Metabolites detected in the urine after folic acid feeding included the unchanged compound, other folates and a number of breakdown products, such as p-acetamidobenzoyl-L-glutamate and p-acetamidobenzoate. This confirms the existence of a folate catabolic pathway in man. Patients with malignant disease excreted less of the dose in urine, incorporated more into the reduced folate pool, and showed decreased catabolism of folate, when compared to controls. 10-Formylfolate was excreted largely unchanged, and appears not to be reduced by man. Also 10-formylfolate interfered with the reduction of folic acid given simultaneously.
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