The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid

A. J. Clifford, A. Arjomand, S. R. Dueker, Philip D Schneider, B. A. Buchholz, J. S. Vogel

Research output: Contribution to journalArticle

58 Citations (Scopus)

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 eases. 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.

Original languageEnglish (US)
Pages (from-to)239-251
Number of pages13
JournalAdvances in Experimental Medicine and Biology
Volume445
StatePublished - 1998

Fingerprint

Folic Acid
Metabolism
Mass spectrometry
Mass Spectrometry
Particle accelerators
Background Radiation
Radiation
Enzyme kinetics
Tritium
Deuterium
Metabolic Networks and Pathways
Isotopes
Nutrients
Volunteers
Animals
Nucleotides
Animal Models
Availability

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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. Advances in Experimental Medicine and Biology, 445, 239-251.

The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid. / Clifford, A. J.; Arjomand, A.; Dueker, S. R.; Schneider, Philip D; Buchholz, B. A.; Vogel, J. S.

In: Advances in Experimental Medicine and Biology, Vol. 445, 1998, p. 239-251.

Research output: Contribution to journalArticle

Clifford, A. J. ; Arjomand, A. ; Dueker, S. R. ; Schneider, Philip D ; Buchholz, B. A. ; Vogel, J. S. / The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid. In: Advances in Experimental Medicine and Biology. 1998 ; Vol. 445. pp. 239-251.
@article{edc48ba174784eb9bab13e391596269c,
title = "The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid",
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 eases. 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.",
author = "Clifford, {A. J.} and A. Arjomand and Dueker, {S. R.} and Schneider, {Philip D} and Buchholz, {B. A.} and Vogel, {J. S.}",
year = "1998",
language = "English (US)",
volume = "445",
pages = "239--251",
journal = "Advances in Experimental Medicine and Biology",
issn = "0065-2598",
publisher = "Springer New York",

}

TY - JOUR

T1 - The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid

AU - Clifford, A. J.

AU - Arjomand, A.

AU - Dueker, S. R.

AU - Schneider, Philip D

AU - Buchholz, B. A.

AU - Vogel, J. S.

PY - 1998

Y1 - 1998

N2 - 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 eases. 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.

AB - 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 eases. 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.

UR - http://www.scopus.com/inward/record.url?scp=0031848359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031848359&partnerID=8YFLogxK

M3 - Article

C2 - 9781393

AN - SCOPUS:0031848359

VL - 445

SP - 239

EP - 251

JO - Advances in Experimental Medicine and Biology

JF - Advances in Experimental Medicine and Biology

SN - 0065-2598

ER -