A qualitative study on vanadate effects in the tetrahydrofolate-dependent formate transfer in vitro and in vivo in mice.
Parenteral administration of sodium vanadate (NaVO3, 22 mg/kg b.w., i.p.) to mice depresses the oxidation rate of [14C]formate to [14C]CO2, as determined by radioactive breath analysis. The heavy metal-induced inhibition is relatively fast in onset, fairly intense (up to 80% inhibition), of short duration (about 2 h) and strongly correlated to the presence of vanadate (in the pentavalent state) in plasma. The [14C]CO2 exhalation rate from [14C]bicarbonate is less affected by vanadate in vivo, thereby suggesting a specific interference of vanadium in the intermediate step of formate oxidation to HCO3-. In vitro in mouse liver cytosolic fractions vanadate inhibits the enzymatic transfer of formate to tetrahydrofolic acid. The inhibition is accomplished by a vanadate-dependent oxidative degradation of tetrahydrofolate. In contrast, the concentrations of N5-methyltetrahydrofolate, dihydrofolate and folate remain unchanged upon in vitro-exposure to vanadate. The in vitro studies thus might explain the observed inhibition of formate oxidation to carbon dioxide in vivo by a vanadate-evoked depletion of its biological carrier tetrahydrofolic acid. Whether the interference in tetrahydrofolate metabolism also occurs under in vivo conditions, remains to be elucidated.
D000818:Animals; D001693:Biological Transport, Active; D002245:Carbon Dioxide / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D005574:Formate-Tetrahydrofolate Ligase / Q000378:metabolism; D005561:Formates / Q000378:metabolism*; D006207:Half-Life; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D013763:Tetrahydrofolates / Q000378:metabolism*; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology*
D005561:Formates; D013763:Tetrahydrofolates; D014639:Vanadium; D002245:Carbon Dioxide; D014638:Vanadates; D005574:Formate-Tetrahydrofolate Ligase