Abstract
Folate is an essential nutrient that is involved in many metabolic pathways, including amino acid interconversions and nucleotide (DNA) synthesis. In genetically susceptible individuals and populations, dysfunction of folate metabolism is associated with severe illness. Despite the importance of folate, major gaps exist in our quantitative understanding of folate metabolism in humans. The gaps exist because folate metabolism is complex, a suitable animal model that mimics human folate metabolism has not been identified, and suitable experimental protocols for in vivo studies in humans are not developed.
In general, previous studies of folate metabolism have used large doses of high specific activity tritium and 14C-labeled folates in clinical patients. While stable isotopes such as deuterium and 13C-labeled folate are viewed as ethical alternatives to radiolabeled folates for studying metabolism, the lack of sensitive mass spectrometry methods to quantify them has impeded advancement of the field using this approach.
In this chapter, we describe a new approach that uses a major analytical breakthrough, Accelerator Mass Spectrometry (AMS). Because AMS can detect attomole concentrations of 14C, small radioactive dosages (nCi) can be safely administered to humans and traced over long periods of time. The needed dosages are sufficiently small that the total radiation exposure is only a fraction of the natural annual background radiation of Americans, and the generated laboratory waste may legally be classified non-radioactive in many cases.
The availability of AMS has permitted the longest (202 d) and most detailed study to date of folate metabolism in a healthy adult human volunteer. Here we demonstrate the feasibility of our approach and illustrate its potential by determining empirical kinetic values of folate metabolism. Our data indicate that the mean sojourn time for folate is in the range of 93 to 120 d. It took ≥ 350 d for the absorbed portion of small bolus dose of 14C-folic acid to be eliminated completely from the body.
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References
Bills ND; Koury MJ; Clifford AJ; Dessypris EN. Ineffective hematopoiesis in folate deficient mice. Blood, 1972, 79:2273–2280.
Butterworth CE; Baugh CM; Krumdieck CL. A study of folate absorption and metabolism in man utilizing carbon-14-labeled polyglutamates synthesized by the solid phase method. J Clin Invest, 1969, 48:1131–1142.
Carl GF; Hudson FZ; McGuire BS. Phenytoin induced depletion of folate in rats originates in liver and involves a mechanism that does not discriminate folate form. J Nutr, 1997, 127:2231–2238.
Chanarin I; Bennett M. The disposal of small doses of intravenously injected folic acid. Brit J Haematol, 1962, 8:28–35.
Creek MR; Frantz CE; Fultz E; Haack K; Redwine K; Shen N; Turteltaub KW; Vogel JS. C-14 AMS quantification of biomolecular interactions using microbore and plate separations. Nuc Inst & Meth, 1994, B92:454–458.
Herbert V. Experimental nutritional folate deficiency in man. Trans Assoc Am Phys, 1962, 75:307–320.
Herbert V. Nutritional requirements for vitamin B12 and folic acid. Am J Clin Nutr, 1968, 21:743–752.
Hoppner K; Lampi B. Folate levels in human liver from autopsies in Canada. Am J Clin Nutr, 1980, 33:862–864.
Krumdieck CL; Fukushima K; Fukushima T; Shiota T; Butterworth CE. Long-term study of the excretion of folate and pterins in a human subject after ingestion of 14C-folic acid, with observations on the effect of diphenylhydantoin administration. Am J Clin Nutr, 1978, 31:88–93.
Lewis DP; Van Dyke DC; Willhite LA; Stumbo PJ; Berg MJ. Phentoin-folic acid interaction. Ann Pharmacotherapy; 1995, 29:726–735.
Ma J; Stampfer MJ; Giovannucci E; Artigas C; Hunter DJ; Fuchs C; Willett WC; Scihub J; Hennekens CH; Rozen, R. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res, 1997, 57:1098–1102.
McPartlin J; Courtney G; McNulty H; Weir D; Scott J. The quantitative analysis of endogenous folate catabolites in human urine. Anal Biochem, 1992, 206:256–261.
Pella E. Elemental organic analysis. Am Lab, 1990; 22:116–125.
Perloff BP; Butrum RR. Folacin in selected foods. J Am Diet Assoc, 1977, 70:161–172.
Plante LT; Williamson KL; Pastore EJ. Preparation of folic acid specifically labeled with carbon-13 in the benzoyl carbonyl. Meth Enzym, 1980, 66: 533–535.
Rosenberg IH; Hachey DL; Beer DE; Klein PD. Proceedings of the First International Conference on Stable sotopes in Chemistry, Biology and Medicine. Klein PD; Peterson SV; Eds. USAEC Conference Series # 730525. USAEC, Office of Information Services, Technical Information Center: Springfield, VA. 1973, pp. 421–427.
Shane B. Folylpolyglutamate synthesis and role in the regulation of one-carbon metabolism. Vit Horm. 1989,45:263–333.
Shane B. Folate metabolism, in: Folic Acid Metabolism in Health and Disease. Piciano MF; Stokstad ELR; Gregory JF; Eds. Wiley-Liss, Inc.: New York. 1990, pp. 65–78.
Shane B. Folate chemistry and metabolism, in: Folate in Health and Disease. Bailey LB; Ed. Marcel Dekker, Inc.: New York. 1995, pp. 1–22.
Steinberg SE. Mechanisms of folate homeostatsis. Am J Physiol, 1984, 246: G319–G324.
Stites TE; Bailey LB; Scott KC; Toth JP; Fisher WP; Gregory JF III. Kinetic modeling of folate metabolism through use of chronic administration of deuterium-labeled folic acid in men. Am J Clin Nutr, 1997, 65:53–60.
Stokstad ELR. Historical perspective on key advances in the biochemistry and physiology of folates, in: Folic Acid Metabolism in Health and Disease. Piciano MF; Stokstad ELR; Gregory JF; Eds. Wiley-Liss, Inc.: New York. 1990, pp. 1–21.
Tamura T. Microbiological assay of folates, in: Folic Acid Metabolism in Health and Disease. Piciano MF; Stokstad ELR; Gregory JF; Eds. Wiley-Liss, Inc.: New York. 1990, pp. 121–137.
Vogel JS. Rapid production of graphite without contamination for biological AMS. Radiocarbon, 1992, 34:344–350.
Vogel JS; Turteltaub KW. Biomolecular tracing through accelerator mass spectrometry. Trends Anal Chem, 1992, 11:142–149.
Vogel JS; Turteltaub KW. Accelerator mass spectrometry as a bioanalytical tool for nutrition research. Adv Exptl Med Biol, 1998; this volume.
Wagner C. Biochemical role of folate in cellular metabolism, in: Folate in Health and Disease. Bailey LB; Ed. Marcel Dekker, Inc.: New York. 1995, pp. 23–42.
Weil A; Caldwell J; Strolin-Benedetti M. The metabolism and disposition of fenofibrate in rat. Drug Metab Dispos, 1988; 16:302–309.
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Clifford, A.J., Arjomand, A., Dueker, S.R., Schneider, P.D., Buchholz, B.A., Vogel, J.S. (1998). The Dynamics of Folic Acid Metabolism in an Adult Given a Small Tracer Dose of 14C-Folic Acid. In: Clifford, A.J., Müller, HG. (eds) Mathematical Modeling in Experimental Nutrition. Advances in Experimental Medicine and Biology, vol 445. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1959-5_15
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DOI: https://doi.org/10.1007/978-1-4899-1959-5_15
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