The role of tetrahydrofolate dehydrogenase in the hepatic supply of tetrahydrobiopterin in rats

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Abstract
The reduction of 7,8-dihydrobiopterin to 5,6,7,8-tetrahydrobiopterin by rat liver tetrahydrofolate dehydrogenase (5,6,7,8-tetrahydrofolate-NAD oxidoreductase, EC 1.5.1.3) is competitively inhibited by trimethoprim lactate (apparent Ki 0.285 .mu.M). An apparent Km of 43 .mu.M 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. I.p. administration of trimethoprim had no significant effect on the hepatic supply of tetrahydrobiopterin in rats.