ISSN:
1432-1912
Keywords:
Vanadate
;
Formate
;
In vivo drug metabolism
;
Tetrahydrofolate
;
[14C]CO2 Exhalation analysis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00177760
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