AbstractAbstract
[en] The synthesis and in vivo application of stable-isotopically labeled folic acid was investigated to devise methods suitable for studies of folate metabolism in human subjects. Glutamate-labeled tetradeutero-pteroylglutamic acid (d4-folic acid) was prepared by mixed anhydride coupling of N10-trifluoroacetylpteroic acid and dimethyl L-[3,3,4,4-2H4]glutamic acid, saponification in sodium deuteroxide, and chromatographic purification. Retention of the isotopic label was verified by proton NMR and mass spectrometry of the para-aminobenzoylglutamic acid product of C9-N10 bond cleavage. A method was devised for determination of of isotopic enrichment of urinary d4-folates derived from orally administered d4-folic acid using affinity chromatographic purification, chemical cleavage of the C9-N10 bond, HPLC isolation of the p-[2H4]aminobenzoylglutamate product, followed by negative-ion chemical-ionization gas chromatography/mass spectrometry. Data concerning the urinary excretion of d4-folates derived from an oral dose of d4-folic acid in an adult human are presented
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AMINO ACIDS, ANIMALS, BIOLOGICAL MATERIALS, BIOLOGICAL WASTES, BLOOD COAGULATION FACTORS, BODY FLUIDS, CARBOXYLIC ACIDS, CHROMATOGRAPHY, CLEARANCE, COAGULANTS, DRUGS, HEMATOLOGIC AGENTS, HETEROCYCLIC COMPOUNDS, HYDROGEN ISOTOPES, HYDROXY COMPOUNDS, INTAKE, ISOTOPE APPLICATIONS, ISOTOPES, LIGHT NUCLEI, MAGNETIC RESONANCE, MAMMALS, MATERIALS, NUCLEI, ODD-ODD NUCLEI, ORGANIC ACIDS, ORGANIC COMPOUNDS, ORGANIC NITROGEN COMPOUNDS, PRIMATES, PTERIDINES, RESONANCE, SEPARATION PROCESSES, SPECTROSCOPY, STABLE ISOTOPES, SYNTHESIS, VERTEBRATES, VITAMIN B GROUP, VITAMINS, WASTES
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AbstractAbstract
[en] A method was devised for the synthesis of 3', 5'-[2H2]folic acid (d2-folic acid) for use in studies of folate metabolism in human beings. Labeling was accomplished by catalytic dehalogenation of 3', 5'-dibromofolate with deuterium gas and palladium/carbon catalyst. d2-Folic acid was separated from reduced forms and residual 3'-monobromofolate by chromatography on DEAE-Sephadex. Analysis by proton NMR and mass spectrometry indicated 70-75% deuteration of the 3',5'-positions and lack of deuteration at other carbons. (author)
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GRANT 86-CRCR-1-1938
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Journal of Labelled Compounds and Radiopharmaceuticals; ISSN 0362-4803; ; CODEN JLCRD; v. 25(12); p. 1349-1359
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AMINO ACIDS, BLOOD COAGULATION FACTORS, CARBOXYLIC ACIDS, COAGULANTS, DRUGS, HEMATOLOGIC AGENTS, HETEROCYCLIC COMPOUNDS, HYDROGEN COMPOUNDS, HYDROXY COMPOUNDS, LABELLED COMPOUNDS, MATERIALS, ORGANIC ACIDS, ORGANIC COMPOUNDS, ORGANIC NITROGEN COMPOUNDS, PTERIDINES, RADIOACTIVE MATERIALS, SYNTHESIS, VITAMIN B GROUP, VITAMINS
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AbstractAbstract
[en] The bioavailability of orally administered mono- and polyglutamyl folates was examined in humans by using stable-isotope methods. [3',5'-2H2]Folic acid (d2-FA) and [3',5'-2H2]pteroylhexaglutamate (d2-PteGlu6) were prepared for oral administration and (glu-2H4)folic acid (d4-FA) was prepared for intravenous (iv) injection. In two trials, adult males (n = 7) on a folate saturation regimen (2 mg/d) were given a single 677-nmol oral dose of either d2-FA or d2-PteGlu6 in apple juice along with an iv injection of 502 nmol d4-FA as a control. Urine was collected for 48 h and the isotope labeling of urinary folates determined by mass spectrometry. The excretion ratio of urinary folates (% of d2-folate dose/% of d4-folate dose) resulting from oral d2-FA and iv d4-FA was 1.45 +/- 0.10 (mean +/- SEM) whereas the ratio for oral d2-PteGlu6 and iv d4-FA was 0.67 +/- 0.04. These results indicate that the d2-PteGlu6 is available to humans as a source of folate although its bioavailability is substantially less than that of d2-FA under these conditions
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AMINO ACIDS, ANIMALS, BIOLOGICAL MATERIALS, BIOLOGICAL WASTES, BLOOD COAGULATION FACTORS, BODY FLUIDS, CARBOXYLIC ACIDS, COAGULANTS, DRUGS, HEMATOLOGIC AGENTS, HETEROCYCLIC COMPOUNDS, HYDROGEN ISOTOPES, HYDROXY COMPOUNDS, INTAKE, ISOTOPE APPLICATIONS, ISOTOPES, LIGHT NUCLEI, MAMMALS, MATERIALS, MATHEMATICS, NUCLEI, ODD-ODD NUCLEI, ORGANIC ACIDS, ORGANIC COMPOUNDS, ORGANIC NITROGEN COMPOUNDS, PRIMATES, PTERIDINES, SPECTROSCOPY, STABLE ISOTOPES, STATISTICS, VERTEBRATES, VITAMIN B GROUP, VITAMINS, WASTES
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