The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

/pdf/biomarkers-of-nutrition-for-development-bond-iron-review-4ibc6okj7y.pdf

Biomarkers of Nutrition for Development (BOND)-Iron Review.

Fat-soluble vitamins Vitamin A and Carotenoids Review Properties Methods Method Protocols Vitamin D Review Properties Methods Method Protocols Vitamin E: Tocopherols and Tocotrienols Review Properties Methods Method protocols Vitamin K Review Properties Methods Method protocols 10:40:09 AM Water-soluble vitamins Ascorbic Acid: Vitamin C Review Properties Methods Status of Vitamin C Analysis Method Protocols Thiamin Review Properties Methods Method Protocols Riboflavin Review Properties Methods Method Protocols Niacin Review Properties Methods Method Protocols Vitamin B6 Review Properties Methods Method Protocols Folate and Folic Acid Review Properties: The Microgram Dietary Folate Equivalents Method Protocols Vitamin B12 Review Properties Methods Method Protocols Biotin Review Properties Methods Pantothenic Acid Review Properties Methods Multianalyte Methods for Analysis of the Fat- and Water-Soluble Vitamins Fat-Soluble Vitamins Water-Soluble Vitamins

Vitamin Analysis for the Health and Food Sciences

La polyglutamation est assuree par la folyl polyglutamyl synthetase. Leur etude decrit l'importance pharmacologique de la polyglutamation du methotrexate

/pdf/polyglutamation-of-methotrexate-is-methotrexate-a-prodrug-1knaksaak0.pdf

Polyglutamation of methotrexate. Is methotrexate a prodrug

The physiological importance of folylpolyglutamates is now well established. These derivatives are the intracellular substrates and regulators of one-carbon metabolism, and their synthesis is required for normal folate retention by tissues. Over the last few years, a considerable amount of information has been obtained on the mechanism by which these compounds are synthesized, on how this synthesis is regulated, and on the effects of the polyglutamate chain on the interaction of folate substrates and inhibitors with folate-dependent enzymes. Many regulatory implications have been suggested by these studies, but the physiological relevance of some of these observations remains to be explored. Folates in mammalian tissues are metabolized to polyglutamates of chain lengths considerably longer than that required for folate retention, but the metabolic advantages of this are not entirely clear. Several in vivo model systems have been developed to explore the functioning of specific folylpolyglutamate chain lengths in metabolic cycles of one-carbon metabolism, and these are likely to shed further light on this point. The role of folate-binding proteins in folate transport, the metabolic role of glutamylhydrolases, and the role of folylpolyglutamates in putative multifunctional protein complexes are also areas that are being actively pursued at present and are likely to produce new insights in the future. Recent studies on the retention of antifolates by cells and on their substrate efficacy for folylpolyglutamate synthetases have also suggested mechanisms for the differential cytotoxicity of these agents for different tissues.

Folylpolyglutamate Synthesis and Role in the Regulation of One-Carbon Metabolism

The studies discussed in this review support the view that biochemical and clinical symptoms common to both folate and vitamin B12 deficiency are due to the induction of a functional folate deficiency, which in turn is induced by cobalamin deprivation. The interrelationship between these two vitamins is best explained by the methyl trap hypothesis stating that vitamin B12 deficiency can lead to lowered levels of methionine synthetase, which results in a functional folate deficiency by trapping an increased proportion of folate as the 5-methyl derivative. In addition, as 5-methyl-H4PteGlu is a poor substrate for folylpolyglutamate synthetase, there is a decreased synthesis of folylpolyglutamates and consequently a decreased retention of folates by tissues. The real folate deficiency that ensues because of decreased tissue folate levels is probably as important physiologically as the functional deficiency caused by the methyl trap. The sparing effect of methionine can be explained by adenosylmethionine inhibition of methylenetetrahydrofolate reductase, which would prevent the buildup of 5-methyl-H4PteGlun. A deficiency in vitamin B12 would not, in itself, be sufficient to cause a disturbance in folate metabolism. The deficiency would have to result in lowered methyltransferase levels before any such disturbance would be manifest.

Vitamin B12-Folate Interrelationships

The purification and properties of folylpolyglutamate synthetase from Corynebacterium sp, and some properties of partially purified enzyme from Lactobacillus casei, Streptococcus faecalis, Neurospora crassa, pig liver, and Chinese hamster ovary cells, are described.

https://link.springer.com/content/pdf/10.1007/BF00232575.pdf

Folylpoly-gamma-glutamate synthesis by bacteria and mammalian cells.

Separation and identification of pteroylpolyglutamates by polyacrylamide gel chromatography.

Cleavage of naturally occurring folates to unsubstituted p-aminobenzoylpoly-γ-glutamates

The interrelationship between vitamin B12 and folate metabolism in man is best illustrated by the hematologically indistinguishable, macrocytic megaloblastic anemia resulting from a deficiency of either vitamin. Large pharmacological doses of either vitamin will elicit a hematological response in patients suffering from a deficiency of either or even both vitamins (Marshall and Jandl, 1960; Zalusky et al., 1962). For instance, large doses of folate cause a temporary or partial hematological remission in pernicious anemia patients but fail to correct the neurological lesions that arise from prolonged vitamin B12 deprivation.

The Interrelationships among Folate, Vitamin B12, and Methionine Metabolism

A radiometric microbiologic assay for vitamin B-6 was applied to food analysis. The method was shown to be specific, reproducible and simpler than the standard turbidimetric microbiologic technique. The analysis of seven commercially available breakfast cereals was compared to a high performance liquid chromatography method. Three out of the seven cereals agreed when assayed with both methods (P greater than 0.1). Four cereals, however, differed in value considerably (P less than 0.05). Further studies are required to determine whether these differences were due to different extraction procedures used. The study showed that the new radiometric-microbiologic method can be used to measure total vitamin B-6 or, combined with a column separation procedure, to analyze for specific forms of the vitamin.

Radiometric--microbiologic assay of vitamin B-6: application to food analysis.

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