Folate Metabolism in the Guinea Pig

Abstract

Following the oral administration of a mixture of
[2-14c]and [3',5',7,9-2H folic acid to normal guinea pigs,
p-acetamidobenzoate (major product) and p-acetamidobenzoyl-
L-glutamate (minor product) were found in the urine. No radioactive
folate was excreted except at very high doses when trace
amounts of folic acid appeared, or after pre-treatment of the
guinea pigs with antibiotics or methotrexate. Up to 20% of an
oral dose of (2~14c] folic acid was found in the expired air.
Only small amounts of radioactive polyglutamates were synthesized
in the liver. Scorbutic guinea pigs similarly dosed gave
qualitatively similar results to normal guinea pigs but catabolized
rather more of the liver polyglutamates.

p-Acetamidobenzoate (major product) and p-acetamidobenzoyi~~—
L-glutamate (minor product) still remained the dominant metabolites
following an_oral dose of a mixture of either (2~14c] ana
(3',5',7,9-2H] 10-formyl-folic acid or of the biologically active
mixture of (2-l4c]ana[3',5',7,9-3H]5-methyltetrahydrofolate.
Ory administration of the 50:50 diastereoisomeric mixture of
a4 4c] 5-methyltetrahydrofolate gave small amounts of 5-methyltetrahydrofolate in the urine but largely breakdown products.

These results contrast sharply with those described for
the rat and man. They show that in the guinea pig all folates
are poorly absorbed from the gut as would be expected from the
nearly neutral acid microclimate. Folic acid and 10-formylfolic
acid are reduced to tetrahydrofolates in the gut. These
tetrahydrofolates and 5-methyltetrahydrofolate acid are
catabolized to p-acetamidobenzoate in the gut. Liver folate
polyglutamates are broken more slowly to p-acetamidobenzoyl-
L-glutamate than in the rat and man as would be expected from
the greater cytosolic reducing capacity of the guinea pig. The
more rapid liver folate breakdown in the scorbutic guinea pig
suggests a steady depletion of folate would occur in man in
scurvy and this will precipitate anaemia.

Date of Award	1982
Original language	English