Effect of chronic phenobarbital treatment on folates and one-carbon enzymes in the rat.

Chronic oral phenobarbital treatment (50 mg/kg every 12 hr for 8 weeks), which was nontoxic and continuously protective against seizures in rats, significantly decreased folate concentration in liver (29%) but not in brain or plasma. The apparent activity of 5,10-methylenetetrahydrofolate reductase (MTR) in liver decreased with initiation of treatment but then increased with a significant correlation to the length of treatment. Phenobarbital also stimulated the activity of this enzyme slightly in vitro. Methionine adenosyltransferase (MAT) activity was inhibited by high concentrations of phenobarbital in vitro but was not affected in vivo. No significant effects of phenobarbital on the activities of serine hydroxymethyltransferase (SHMT) or 5-methyltetrahydrofolate:homocysteine methyltransferase (MHMT) were observed either in vivo or in vitro.