Effect of chronic primidone treatment on folate-dependent one-carbon metabolism in the rat.
Rats were treated chronically with primidone (100 mg/kg/12 hr, p.o.) for up to 8 weeks. The effects of this treatment on one-carbon metabolism were determined in brain and liver. Serine hydroxymethyltransferase activity increased in both brain (44%) and liver (50%). Methylenetetrahydrofolate reductase activity increased in liver (26%) with a significant correlation to the length of treatment, but in brain it was unchanged. Methyltetrahydrofolate:homocysteine methyltransferase activity increased in brain (43%) with a significant correlation to length of treatment, but in liver no effect was observed. Methionine adenosyltransferase activity in brain was significantly lower than control at only one point after 8 weeks of chronic treatment. S-Adenosylmethionine concentration in liver increased gradually (23%) during treatment. S-Adenosylhomocysteine concentrations decreased in brain (33%) and increased in liver (23%) with chronic primidone treatment. These data support the hypothesis that chronic primidone treatment leads to folate depletion through interference with folate metabolism.
D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D005492:Folic Acid / Q000378:metabolism*; D012696:Glycine Hydroxymethyltransferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D011324:Primidone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism
D011324:Primidone; D012436:S-Adenosylmethionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D010088:Oxidoreductases; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D012696:Glycine Hydroxymethyltransferase; D008716:Methionine Adenosyltransferase