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.