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J P Toth

Publications and source records attributed to J P Toth.

29 records · Page 2Linked to original sources
PubMed1992

Relative bioavailability of deuterium-labeled monoglutamyl tetrahydrofolates and folic acid in human subjects.

The bioavailability of orally administered monoglutamyl folic acid and various (6S)-tetrahydrofolates was examined in humans with stable-isotope methods. Folic acid (PteGlu), tetrahydrofolate (H4folate), 5-formyl-H4folate, 10-formyl-H4folate, and 5-methyl-H4folate were prepared for oral administration in 3',5'-2H2 labeled (d2) form, and [glu-2H4]folic acid (d4-PteGlu) was prepared for intravenous injection. In each of five trials, fasting adult males (n = 7) on a folate saturation regimen (2 mg/d) were given a single oral dose of one of the d2-folates in apple juice, as well as an intravenous injection of d4-PteGlu as a control. Urine was collected for 48 h and the isotope labeling of urinary folates determined by mass spectrometry. Isotope excretion ratios of urinary folates were used as criteria of bioavailability (pooled SE = 0.10): PteGlu (1.53, least squares mean), 10-formyl-H4folate (1.02), 5-methyl-H4folate (0.99), 5-formyl-H4folate (0.1.13), and H4folate (0.71). These results indicate that differences exist in the bioavailability of monoglutamyl folates under these experimental conditions. This variation, whether due to differences in absorption or postabsorptive events, must be considered in quantitative studies of folate utilization with this type of protocol.

Administration, Oral↗
PubMed1992

In vivo folate kinetics during chronic supplementation of human subjects with deuterium-labeled folic acid.

Six healthy men (22-31 y) were supplemented for 4 wk with folic acid labeled with deuterium [3',5'-2H2; 3.6 mumol/d (1.6 mg/d)] to permit evaluation of in vivo kinetics of this vitamin. Total folate in urine, serum and erythrocytes was determined by microbiological assay, and isotopic labeling of urinary and erythrocyte folate was determined by gas chromatography-mass spectrometry. During supplementation, serum folate reached maximal concentration in approximately 18 d, whereas excretion of total and deuterium-labeled folates increased rapidly and reached isotopic steady state in 1-2 wk. Isotopic labeling of erythrocyte folate increased continually over the entire supplementation period. Upon cessation of supplementation, red blood cell folate and urinary folate excretion (total and labeled) decreased linearly. The decline in total serum folate could be described with a biexponential model that yielded a slow-phase half-life of 18.7 +/- 2.3 d. This model also indicated a turnover of 4.5% of the total body folate pool per day. Pool sizes of total body folate before and after supplementation (at steady state) were calculated to be 10 mumol (4.4 mg) and 98.9 mumol (43.7 mg), respectively. These kinetic data and stable isotope methodology may be used to address a wide range of experimental questions related to folate metabolism.

Adult↗
PubMed1991

Relative bioavailability of deuterium-labeled monoglutamyl and hexaglutamyl folates in human subjects.

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.

Administration, Oral↗
PubMed1991

Bioavailability of pyridoxine-5'-beta-D-glucoside determined in humans by stable-isotopic methods.

Stable-isotopic methods were employed to evaluate the utilization of dietary pyridoxine-5'-beta-D-glucoside (PN-glucoside), a major form of vitamin B-6 in plant-derived foods, as a source of available vitamin B-6 for adult men (20-35 y old, n = 5). Deuterium-labeled forms of free pyridoxine (PN) and PN-glucoside were compared using the urinary excretion of labeled forms of the vitamin B-6 metabolite 4-pyridoxic acid as the main index of absorption and metabolism. When comparing orally administered, isotopically labeled PN and PN-glucoside in separate groups of subjects, similar bioavailability was observed although within-group variability was high. A dual-label study designed to examine the bioavailability of these compounds when administered simultaneously indicated that the utilization of deuterated PN-glucoside was 58 +/- 13% (mean +/- SEM) relative to that of deuterated PN. PN-glucoside was detected in all urine samples, which provided additional evidence of incomplete metabolic utilization. In contrast, intravenously administered PN-glucoside underwent approximately half the metabolic utilization of oral PN-glucoside. These studies indicate that the bioavailability of dietary PN-glucoside, although incomplete, is substantially greater in humans than previously found in rats. In addition, the difference between oral and intravenous routes suggests a role of beta-glucosidase(s) of the intestinal mucosa, microflora, or both in the release of free PN from dietary PN-glucoside.

Administration, Oral↗
PubMed1990

Perceptual identification, fragment completion, and free recall: concepts and data.

The effects of orthographically distinctive and orthographically common words were compared on tests of free recall, fragment completion, perceptual identification, and lexical decision. Orthographic distinctiveness is argued to effect data-driven processing and, in light of recent theory, should have little effect upon free recall but substantial effects upon fragment completion and perceptual identification. The results showed superior recall and fragment completion of orthographically distinctive words but more accurate perceptual identification of orthographically common words. Latency of lexical decision was longer for orthographically distinctive than for orthographically common words. The visual complexity of orthographically distinctive words may require more extensive sensory processing than is possible within the temporal constraints of perceptual identification tests. The effect of orthographic distinctiveness upon free recall reveals a certain inadequacy in the notion of transfer-appropriate processing.

Cues↗
PubMed1990

Stable-isotope methods for assessment of folate bioavailability.

Research was conducted to determine whether stable-isotope-labeled folates could be employed for studies of folate absorption and metabolism in human subjects. Two deuterium-labeled forms of folic acid were evaluated for simultaneous in vivo use, with quantification of relative bioavailability by measurement of urinary excretion of labeled folates. Adult male subjects (n = 11) were given saturation doses of 2 mg unlabeled folic acid/d for 7 d before the study. After an overnight fast each subject consumed 677 nmol each of 3',5'-labeled bideuterofolic acid and glutamate-labeled tetradeuterofolic acid. The 48-h urinary excretion of deuterated folates represented 5-6% of the ingested dose. The molar ratio of labeled folates in urine was not significantly different from the molar ratio in the ingested dose, which indicated equivalent absorption and metabolism of these labeled forms of the vitamin. These results support the validity of this protocol for in vivo studies of folate bioavailability.

Adult↗
PubMed1988

[14C]acetate incorporation by cultured normal, familial hypercholesterolemia and Down's syndrome fibroblasts.

Fibroblasts from patients with homozygous familial hypercholesterolemia (FH), a disease characterized by accelerated atherogenesis, are known to lack functional low-density-lipoprotein receptors, which ultimately results in increased cholesterol biosynthesis in the cultured cells. [14C]Acetate incorporation in these cells was compared to that of normal fibroblasts and to fibroblasts from patients with Down's syndrome, a disease in which atherosclerosis is rare. Total [14C]acetate incorporation did not differ significantly between normal and Down's fibroblasts, nor did its partitioning into the hexane-extractable and aqueous fractions of the cell hydrolysates. [14C]Acetate incorporation was much greater in FH cells in both the aqueous and hexane-extractable fractions. Preincubation in fetal bovine serum increased acetate incorporation only by FH cells, while 50 micrograms low-density lipoprotein/ml medium depressed acetate incorporation in all three groups. A C27 sterol, identified by gas chromatography-mass spectrometry as a probable isomer of cholesterol, was present in small amounts in FH fibroblasts, but was not detectable in the normal or Down's cells. The absolute amounts of [14C]acetate incorporated into the non-sterol lipids were greater in the FH fibroblasts, indicating that these cells may have to synthesize, in addition to cholesterol, other required cellular lipids which are delivered to the normal cells by low-density lipoproteins.

Acetates↗
PubMed1988

Chemical synthesis of deuterated folate monoglutamate and in vivo assessment of urinary excretion of deuterated folates in man.

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.

Administration, Oral↗