The influence of folate antagonists on the metabolism of folic acid and its reduced derivatives in rat liver and kidney.

Abstract

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.

• Authors: U Bühring, Y S Shin, E Fölsch
• Journal: Cancer research (Cancer Res) Vol. 37 Issue 1 Pg. 299-304 (Jan 1977) ISSN: 0008-5472 [Print] United States
• PMID: 830415 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Folic Acid Antagonists
• Formyltetrahydrofolates
• Glutamates
• Tetrahydrofolates
• Folic Acid
• Aminopterin
• Methotrexate

Topics

• Aminopterin (pharmacology)
• Animals
• Folic Acid (metabolism)
• Folic Acid Antagonists (pharmacology)
• Formyltetrahydrofolates (metabolism)
• Glutamates (biosynthesis)
• Kidney (metabolism)
• Liver (metabolism)
• Methotrexate (analogs & derivatives, pharmacology)
• Rats
• Tetrahydrofolates (metabolism)