Folic polyglutamates

Because of the multiplicity of folic acid factors reported in whole blood (Ul), the microbiologic assay for folic acid in whole blood and serum was regarded as valueless (C2, L8, W9) results based on S. faecalis methods (C2, C3) did not contradict this view. Streptococcus faecalis is inferior to L. casei in its utilization of the PGA polyglutamates... 

The chemical structure of folate (or folic acid) is shown in Figure 5.8. In humans, folate usually occurs as polyglutamate derivatives. The active form of folate is THF, sometimes shown as FH4) is derived from folate via two reductase reactions. THF functions as a carrier of one-carbon groups in varying oxidation states (Table 5.1). 

Methotrexate is a folic acid analogue. Its mechanism of action is based on the inhibition of dihydrofolate reductase. Inhibition of dihydrofolate reductase leads to depletion of the tetrahydrofolate cofactors that are required for the synthesis of purines and thymidylate (see Fig. 2). Enzymes that are required for purine and thymidylate synthesis are also directly inhibited by the polyglutamates of methotrexate which accumulate with dihydrofolate reductase inhibition. The mechanisms that can cause resistance include decreased transport of methotrexate into the tumor cells, a decreased affinity of the antifolate for dihydrofolate reductase, increased concentrations of intracellular dihydrofolate reductase and decreased thymidylate synthetase activity. 

Raltitrexed is a folic acid analogue which inhibits thymidylate synthetase. Intracellularly formed raltitrexed polyglutamates are even stronger inhibitors of thymidylate synthetase than the parent compound. Similar to methotrexate polyglutamates... 

Much of the folacin in food is present as conjugated pteroyl polyglutamates. Soybean contains 40% monoglutamate analogues, but in cabbage 90% of folic acid is present in forms... 

The higher RDA is specified to allow for absorption of only 25% of folic acid activity in a manner comparable to the crystalline folic acid and to allow for a wide range of availability of the polyglutamate form (13). 

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. 

Folacin (folic acid) is involved in metabolism and in the biosynthesis of purines and pyrimidines. It is a very stable vitamin but does not occur naturally in feedstuffs. Instead it occurs in reduced forms as polyglutamates, which are readily oxidized. These forms are converted to folic acid in the body. Diets commonly contain sufficient folacin but this is not assured. Folacin is therefore usually included in the vitamin supplement added to poultry diets to ensure adequacy. A deficiency in young chicks or poults results in retarded growth, poor feathering and perosis. Coloured plumage may lack normal pigmentation, and a characteristic anaemia is also present. Cervical paralysis is an additional symptom in deficient turkeys. 

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