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.

Date of Award	1972
Original language	English