Folates polyglutamates

HPLC does not give a good response to long-chain derivatives of folate, therefore, conversion of the natural form of folate, polyglutamates, to mono- or di-glutamate is required. The enzyme used is y-glutamylcarboxypeptidase, extracted from chicken pancreas, hog kidney, or to a lesser extent from... 

Conjugase responds rapidly to zinc depletion and repletion, and it has been suggested that the absorption of a test dose of folate polyglutamates may provide a sensitive index of zinc nutritional status (Canton and Cremin, 1990). The absorption of folate monoglutamates (from pharmaceutical preparations or foods) is not affected. 

Folate polyglutamate synthetase binds ATP, tetrahydrofolate-(oligo)-glutamate, then glutamate sequentially forming an intermediate folate... 

Chronic therapy of experimental animals with primidone depletes liver folate pentaglutamates, suggesting inhibition of folate polyglutamate synthetase (Carl et al 1987). This would be expected to lead to increased excretion of folate metabolites. 

Cassady lA, Budge MM, Healy MJ, and Nixon PF (1980) An inverse relationship of rat liver folate polyglutamate chain length to nutritional folate sufficiency Biochimica et Biophysica Acta 633, 258-68. 

Verlinde, P., Oey, L, Hendrickx, M., and Loey, A. van. 2008. High-pressure treatments induce folate polyglutamate profile changes in intact broccoli (Brassica oleraceae L. cv. Italica) tissue. Food Chemistry 111 220-229. 

The findings of Stephens et al. (SI9) were similar, but they also reported that if tissues are saturated with folate before testing, folate polyglutamate absorption, as measured by rises in serum folate monoglutamate, was of the same degree in women using oral contraceptives and in those who were nonusers. 

In a later study Shojania and Homady (SIO) also failed to find a difference between normal women and users of contraceptive medications when folate and folate polyglutamate absorption was estimated. Subjects were saturated with folate before absorption was studied. A rough correlation was found in both groups of women between original serum folate concentrations and the rise in serum folate after polygluta-... 

These authors previously found (S12) that in all of 16 women who initially had subnormal serum folate concentrations, serum folate concentrations rose within 3 months after OCAs were stopped. Subsequently they reported (SIO) 3 women with low serum folate levels while taking OCAs and low folate polyglutamate absorption that persisted after medication was discontinued. It was of interest that one of these subjects developed gluten-sensitive enteropathy a year later and a second had a family history of that disease. Other case reports of folate deficiency and mild intestinal malabsorption in users of OCAs have appeared (J3, T2, W12). It should be emphasized, therefore, that evidence of impaired folate absorption in women taking these agents may suggest the presence of inapparent small bowel disease. 

At present, therefore, there seems to be little solid documentation for an absorptive defect of folate polyglutamate in normal women taking OCAs, and furthermore, a mechanism for such an impairment is not apparent. 

Little is known about other aspects of folate metabolism, such as the factors that determine plasma clearance, in either normal subjects or users of oral contraceptive steroids. As described earlier, maximum serum folate concentrations after oral folate polyglutamate are lower in contraceptive users than in nonusers, when subjects are not presaturated (S19). This may be due to increased clearance from plasma, because poor absorption was not found. Stephens et al. (S19) felt that this was probably not due to tissue folate depletion because there was no correlation with initial fasting serum folate concentrations. However, erythrocyte folate concentrations were not measured and might have been a better index of tissue saturation with the vitamin. 

N2. Necheles, T. F., and Snyder, L. M., Malabsorption of folate polyglutamates associated with oral contraceptive therapy. N. Engl. J. Med. 282, 858-859 (1970). 

P5. Perry, J., and Chanarin, I., Observations on folate absorption with particular reference to folate polyglutamate and possible inhibitors to its absorption. Gut 13, 544-550 (1972). 

Folate polyglutamates are the preferred substrates for folate-dependent enzymes they are more active metabolically in cells and also better retained in cells than folate monoglutamates. Natural folates found in foods are all conjugated to a polyglutamyl chain containing different numbers of glutamic adds depending on the type of food. 

Because of the problems of determining the biological availability of the various folate polyglutamate conjugates found in foods, reference intakes allow a wide margin of safety, and are based on an allowance of 3 Jg (6.8 nmol) per kg body weight. 

B Reed, D Weir, J Scott. The fate of folate polyglutamates in meat during storage and processing. Am J Clin Nutr 29 1393-1396, 1976. 

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