Much of the folic acid in natural feedstuffs is conjugated with varying numbers of extra glutamic acid molecules. Polyglutamate forms, usually containing three to seven glutamyl residues linked by peptide bonds of folic acid, are the natural coenzymes, being most abundant in every tissue examined (Wagner, 1984). These folic acid glutamates appear to be a biologically inactive storage form. Synthesized folic acid, however, is the monoglutamate form. It has been concluded that there are more biologically active forms of folic acid than any other known vitamin.
Folic acid is a yellowish-orange crystalline powder, tasteless and odorless, and insoluble in alcohol, ether and other organic solvents. It is slightly soluble in hot water in the acid form but quite soluble in the salt form. It is fairly stable to air and heat in neutral and alkaline solution, but unstable in acid solution. From 70% to 100% folic acid activity is destroyed on autoclaving at pH 1 (O'Dell and Hogan, 1943). It is readily degraded by light and ultraviolet radiation. Cooking can considerably reduce the folic acid activity of food.
Polyglutamate forms of folic acid are digested via hydrolysis to pteroylmonoglutamate prior to transport across the intestinal mucosa. The enzyme responsible for the hydrolysis of pteroylpolyglutamate is a carboxypeptidase known as folate conjugase (Baugh and Krumdieck, 1971). Most likely, several conjugase enzymes are responsible for hydrolysis of the long-chain folate polyglutamates to the monoglutamates, which are then taken up by the mucosal cell (Rosenberg and Newmann, 1974). Pteroylmonoglutamate is absorbed predominantly in the duodenum and jejunum, apparently by an active process involving sodium. Kesavan and Noronha (1983) suggest from rat results that luminal conjugase is a secretion of pancreatic origin and that the hydrolysis of polyglutamate forms of folic acid occurs in the lumen rather than at the mucosal surface or within the mucosal cell.
Dietary folates, after hydrolysis and absorption from the intestine, are transported in plasma as monoglutamate derivatives, predominantly as 5-methyl-tetrahydrofolate. The monoglutamate derivatives are then taken up by cells in tissues by specific transport systems. There the pteroylpolyglutamates, the major folic acid form in cells, are built up again in stepwise fashion by an enzyme, folate polyglutamate synthetase.
Specific folate-binding proteins (FBPs) that bind folic acid mono- and polyglutamates are known to exist in many tissues and body fluids including liver, kidney, small intestinal brush border membranes, leukemic granulocytes, blood serum and milk (Tani and Iwai, 1984). The amount of folate-binding protein secreted by the endometrium during pregnancy was not affected by giving sows daily intravenous infusions of iron and tetrahydrofolate (Vallet et al., 1999). Physiologic roles of these FBPs are unknown, although they have been suggested to play a role in folic acid transport analogous to the intrinsic factor in the absorption of vitamin B12. Studies showed that about 79% to 88% of labeled folic acid is absorbed, and that absorption is rapid since serum concentrations usually peak about two hours after ingestion. Serum folate levels for gilts fed a single meal containing varying amounts of supplemental folic acid confirm that maximal levels are obtained within two hours post-feeding (Harper et al., 1991). Kokue et al. (1998) reported that supplemental synthetic folic acid competes with the reduced folates in the intestinal mucosa for the absorption pathway. The mean availability of folic acid in seven separate food items was found to be close to 50%, ranging from 37% to 72% (Babu and Skrikantia, 1976). Folic acid is widely distributed in tissues, largely in the conjugated polyglutamate forms. Urinary excretion of folic acid represents a small fraction of total excretion. Fecal folic acid concentrations are quite high, often higher than intake, representing not only undigested folic acid but, more importantly, the considerable bacterial synthesis of the vitamin in the intestine. Bile contains high levels of folic acid due to enterohepatic circulation, with most biliary folic acid reabsorbed in the intestine.
