Metabolism of dihydroaminopterin and the influence of aminopterin and related derivatives on the metabolism of (−)-5-formyl-tetrahydrofolic acid in Pediococcus cerevisiae

• Published in: Biochimica et biophysica acta Vol. 421; no. 1; pp. 22 - 32
• Main Authors: BUHRING, K, FOLSCH, E
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 14.01.1976
• Subjects: Aminopterin - analogs & derivatives; Aminopterin - metabolism; Aminopterin - pharmacology; Folic Acid Antagonists - metabolism; Formyltetrahydrofolates - metabolism; Methotrexate - analogs & derivatives; Pediococcus - drug effects; Pediococcus - metabolism; Structure-Activity Relationship; Tetrahydrofolates - metabolism; H 2PteGlu; PteGlu n; PteGlu; H 4PteGlu
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(76)90166-5

[ 3H]Dihydroaminopterin, but not [ 3H]methotrexate or [ 3H]aminopterin, was rapidly taken up by resting cells of Pediococcus cerevisiae and inhibited the uptake of (−)-5-formyl-tetrahydrofolic acid to more than 90% at a concentration of 25 μM. On the other hand 5-formyl-tetrahydrofolic acid inhibited the uptake of dihydroaminopterin to a similar extent. Dihydroaminopterin was metabolized by Pediococcus cerevisiae, but not by Lactobacillus casei, to a compound tentatively identified as dihydroaminopterin diglutamate. Methotrexate or aminopterin at a concentration of 25 μM did not inhibit the uptake of 5-formyl-tetrahydrofolic acid in Pediococcus cerevisiae, but inhibited the conversion of this compound to polyglutamate forms almost completely at a level of 2.5 μM.