Tetrahydrobiopterin-dependent nitrite oxidation to nitrate in isolated rat hepatocytes.

We have found that isolated rat hepatocytes and cell extracts catalyze the stoichiometric conversion of nitrite (either as a product of the oxidation of endogenously synthesized nitric oxide or added as sodium nitrite) to nitrate, which in extracts requires the presence of tetrahydrobiopterin and is inhibited by cyanide but apparently not by carbon monoxide. The reaction is sensitive to heat denaturation and does not involve oxidation of NO2- by a peroxidative or radical oxygen mechanism. These results indicate the presence of a hitherto undescribed mammalian mechanism of inorganic nitrogen oxide oxidation that may be a protective mechanism against one potentially damaging effect of endogenous .NO production (NO2- formation), and also that assays of .NO formation based on NO2- determination alone may be an inaccurate measurement of this activity.