The influence of folate antagonists on the metabolism of folic acid and its reduced derivatives in rat liver and kidney.
Uptake and conversion of [3H]folic acid to polyglutamate derivatives by rat liver and kidney were inhibited by methotrexate or aminopterin (15 mg/kg body weight) and DL-tetrahydromethotrexate (30 mg/kg body weight). In contrast, these antagonists did not influence the conversion of L-5-formyl-[3H]tetrahydrofolic acid or L-5-methyl[3H]tetrahydrofolic acid to polyglutamine derivatives and had little effect on the uptake of reduced folate derivatives. When [3H]methotrexate, [3H]aminopterin, and DL-[3H]tetrahydromethotrexate were administered in small amounts (15 mug/kg body wieght), no metabolites of these compounds were observed. However, at higher doses of [3H]methotrexate (300 mug/kg body weight), more than 30% of the radioactivity remaining in the tissue 24 hr after administration could be attributed to a metabolite of methotrexate. This metabolite was tentatively identified as methotrexate diglutamate.[1]References
- The influence of folate antagonists on the metabolism of folic acid and its reduced derivatives in rat liver and kidney. Bühring, U., Shin, Y.S., Fölsch, E. Cancer Res. (1977) [Pubmed]
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