Dietary folates

The risk of colon cancer appears to be inversely related to calcium and folate intake. Calciums protective effect may be related to a reduction in mucosal cell proliferation rates or through its binding to bile salts in the intestine, whereas dietary folate helps in maintaining normal bowel mucosa. Additional micronutrient deficiencies have been demonstrated through several studies to increase colorectal cancer risk and include selenium, vitamin C, vitamin D, vitamin E, and 3-carotene however, the benefit of dietary supplementation does not appear to be substantial.11... 

Enzymatic reactions that use folates. Section 1 shows the vitamin B12 -dependent reaction that allows most dietary folates to enter the tetrahydrofolate cofactor pool and becomes the "folate trap" in vitamin B12 deficiency. Section2 shows the dTMP cycle. 

Unaltered folic acid is readily and completely absorbed in the proximal jejunum. Dietary folates, however, consist primarily... 

JB Ubbink, PJ Becker, and WJH Vermaak. Will an increased dietary folate intake reduce the incidence of cardiovascular disease Nutr Rev 54 213-216, 1996. 

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. 

L8. Lumb, M., Perry, J., Deacon. R., and Chanarin, I., Recovery of tissue folates after inactivation of cobalamin by nitrous oxide. The significance of dietary folate. Am. /. Clin. Nutr. 34, 2418-2422 (1981). 

The mechanism by which dietary folate supplementation prevents NTDs is not understood (Prevention of Neural Tube Defects Results of... 

Suarez, L., Hendricks, K. A., Cooper, S. P., Sweeney, A. M., Hardy, R. J., and Larsen, R. D. (2000). Neural tube defects among Mexican Americans living on the US-Mexico border Effects of folic acid and dietary folate. Am. J. Epidemiol. 152(11), 1017-10123. 

Most of the dietary folate undergoes reduction and methylation within the intestinalmucosa and what enters theportal bloodstream is alargely 5-methyl-tetrahydrofolate. Single doses of more than about 200 /xg of folic acid saturate the intestinal dUiydrofolate reductase, so that free folic acid is absorbed and circulates in the bloodstream. It can be taken up by tissues, reduced to tetrahy-drofolate, and utilized. 

Most dietary folate is reduced and methylated to methyl-tetrahydro-folate in the intestinal mucosa (Section 10.2.1). Intestinal mucosal ceUs have a rapid turnover, typicaUy 48 hours from proliferation in the crypt to shedding at the tip of the vUlus. This means that an unstable variant of the enzyme, which loses activity over a shorter time than the normal enzyme, is probably irrelevant in ceUs that have such a rapid turnover. A high intake of folate would therefore result in a relatively high rate of supply of methyl-tetrahydrofolate to cells, arising from newly absorbed folate, so that impaired turnover of folate within cells would be less important. 

Hirono H, Wada Y (1978) Effects of dietary folate deficiency on developmental increase of myehn lipids in rat brain. J Nutr 108(5) 766-772... 

The enzyme dihydrofolic acid (DHF) S5mthase (see below) converts p-aminobenzoic acid (PABA) to DHF which is subsequently converted to tetrahydric folic acid (THF), purines and DNA. The sulphonamides are structurally similar to PABA, successfully compete with it for DHF s)mthase and thus ultimately impair DNA formation. Most bacteria do not use preformed folate, but humans derive DHF from dietary folate which protects their cells from the metabolic effect of sulphonamides. Trimethoprim acts at the subsequent step by inhibiting DHF reductase, which converts DHF to THF. The drug is relatively safe because bacterial DHF reductase is much more sensitive to trimethoprim than is the human form of the enzyme. Both sulphonamides and trimethoprim are bacteriostatic. 

Other effects include Dupu5dren s contracture and pseudolymphoma. Some degree of macrocyto-sis is common but anaemia probably occurs only when dietary folate is inadequate. This responds to folate supplement (the requirement for folate is increased, as it is a cofactor in some hydroxylation reactions that are accelerated by enzyme induction by phenytoin). Osteomalacia due to increased metabolism of vitamin D occurs after years of therapy. 

Folate is a water-soluble vitamin. The recommended daily allowances (RDAs) of folate for the adult man and woman are 20fJ and 101) pg, respectively. The RDA is defined in the Preface. Folate is critically important for growth, and for this reason it is required in increased amounts during pregnancy (400 pg. The need for dietary folate remains elevated after pregnancy and during lactation because of the Irans-... 

Tho data in Table 9.1 are from an cxporlment involving foly] poly glutamate synthase. The enzyme was obtained in purified form from liver and was mixed with glutamic acid, ATP, and the indicated form of foiate. The mixture was incubated to permit the enzyme to catalyze the attachment of glutamafc residues to the folate. What do you think would be the effect of a vitamin Bij deficiency on the rate of polyglutamation of dietary folates, flint Dietary folates occur in the bloodstream initially as 5-melhyl-l UPteGtu, and enter the cell in this form. 

Folale deficiency occurs in pregnancy on a wide scale. The increased utilization of the vitamin by die fetus and related tissues, as well as the secretion in milk during lactation, can place an increased demand on the dietary folates consumed by the mother. Sea ere folate deficiency leads to megaloblastic anemia. This disease, in which the synthesis of red blood cells is impaired, tends to occur with pregnancy in underdeveloped countries, but usually not in North America or Europe, Goat s milk is a poor source of folate and vitamin Bjj. Ovcrrchancc on goal s milk as a source of food for infants can result in a deficiency in these vitamins and in anemia. 

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