The role of tetrahydrofolate dehydrogenase in the hepatic supply of tetrahydrobiopterin in rats.
The reduction of 7,8-dihydrobiopterin to 5,6,7,8-tetrahydrobiopterin by rat liver tetrahydrofolate dehydrogenase (5,6,7,8-tetrahydrofolate-NADP+ oxidoreductase, EC 1.5.1.3) is competitively inhibited by trimethoprim lactate (apparent Ki 0.285 muM). An apparent Michaelis constant of 43 muM for dihydrobiopterin was obtained, which is 430 times higher than the reported Km for dihydrofolate with this enzyme. The reduction of dihydrobiopterin is thus more susceptible to inhibition by trimethoprim lactate than is the reduction of dihydrofolate. However, intraperitoneal administration of trimethoprim had no significant effect on the hepatic supply of tetrahydrobiopterin in rats.
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism*; D005260:Female; D005493:Folic Acid Antagonists; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D011621:Pteridines / Q000378:metabolism*; D051381:Rats; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*; D014295:Trimethoprim / Q000494:pharmacology
D005493:Folic Acid Antagonists; D011621:Pteridines; D001708:Biopterins; D014295:Trimethoprim; D013762:Tetrahydrofolate Dehydrogenase; C003402:sapropterin