The Fate of Folic Acid and Related Compounds in the Rat

Abstract

The physiological disposition and metabolism of : folates was studied by purification, characterisation and specific radioactivity determinations of compounds derived from oral doses of labelled folates. At doses of 22 and 320ug of pteroyl-L-glutamic acid/ kg, 50 and 25% respectively was absorbed, With doses of 320ug of [214-C]pteroyl-L-glutamic acid/kg, radioactivity was detected in the peripheral circulation 10 minutes after administration. Pteroyl-L-glutemic acid was absorbed without metabolism and was present in systemic blood for up to 4 hours after administration. With doses of pteroyl-L-glutamic acid from 3.1 to 56ug/kg approximately 6% of the dose was excreted in 24 hours; whilst at 320ug/kg 30% was excreted mainly in the 2 to 4 hour period. Three urinary folates were isolated. One sf the major metabolites was 5-methyltetrahydro-pteroylglutamic acid. The others were unidentified but were not pteroylglutamic acid, 7,8-dihydro-, 5,6,7,8-tetrahydro-, 5- or 10-formyltetrahydro-, 5,10~methylidyne-tetrahydro-, 5,formimidoyltetrahydro-, 5,10-methylene-tetrahydro-, 5-methyltetrahydro-pteroylglutamic acid, nor any decomposition products of these compounds formed during isolation. Labelled unconjugated pteridines were absent. Six hours after administration of pteroyl-L-glutamic acid, more than seven labelled compounds were isolated from liver homogenates. Extractions performed up to 10 days after administration or after prior starvation only conjugates, 5-methyltetrahydro~pteroylglutamate was the major monoglutamate and represented 10% of the total hepatic folates. The physiological disposition of the natural diastereoisomer of 5-methyltetrahydro-pteroylglutamate was similar to that of pteroylglutamate. At a dose of 84u¢/keg, 80% of the urinary folates was 5-methyltetrahydropteroylglutamate, but at lower doses a greater proportion was present as metabolites. The major unidentified metabolite excreted after pteroylglutamic acid administration showed a similar absorption and excretion pattern to 5-methyltetrahydropteroylglutamic acid and was metabolised to 5-methyltetrahydro-pteroylgiutamate. The results are discussed with reference to the nutritional, metabolic and clinical importance of folates in previous work.