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.
D000630:Aminopterin / Q000494:pharmacology; D000818:Animals; D005492:Folic Acid / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005575:Formyltetrahydrofolates / Q000378:metabolism; D005971:Glutamates / Q000096:biosynthesis; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008727:Methotrexate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D013763:Tetrahydrofolates / Q000378:metabolism*
D005493:Folic Acid Antagonists; D005575:Formyltetrahydrofolates; D005971:Glutamates; D013763:Tetrahydrofolates; D005492:Folic Acid; D000630:Aminopterin; D008727:Methotrexate