Folic acid conjugase

Unaltered folic acid is readily and completely absorbed in the proximal jejunum. Dietary folates, however, consist primarily of polyglutamate forms of N 5-methyltetrahydrofolate. Before absorption, all but one of the glutamyl residues of the polyglutamates must be hydrolyzed by the enzyme -1-glutamyl transferase ("conjugase") within the brush border of the intestinal mucosa. 

Free folate, released by conjugase action, is absorbed by a carrier-mediated mechanism in the jejunum. However, the folate in mUk is mainly bound to a specific binding protein (which has been used in radioligand binding assays for folate) the protein-folate complex is absorbed intact, mainly in the ileum, by a mechanism that is distinct from the j ejunal transport system for free folate. The biological availability of folate from miLk, or of folate from diets to which mUk has been added, is considerably greater than that of unbound folate, whereas that of folate from cereal foods, or of free folic acid taken with cereal foods, is lower. 

The quantitation of folate absorption under both normal and abnormal conditions remains difficult, especially in view of the variety of forms of folate that may be consumed. Absorption of each of these forms has not been studied in detail. Since OCAs have been postulated by some to interfere with folate conjugase (see below), it is especially important for this discussion to compare the efficiency of absorption of conjugated and unconjugated forms of folic acid. 

B. E. Wright, J. Biol. Chem. 219, 873 (1956). It is probable that the natural cofactors in animal systems also are conjugates of tetrahydrofolic acid. Assays of fresh extracts for folio acid vitamin activity reveal the presence of very little active material in most tissues, but the amounts increase upon autolysis. Both oxidized and reduced pteridines occur as folic acid derivatives containing one or more additional glutamic acid residues. Enzymes that hydrolyze peptide bonds to liberate folic acid activity have been found in many organisms and have been named conjugases [E. L. R. Stokstad, Vitamins 3, 163 (1954)]. 

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