Differential Kinetic Behavior and Distribution for Pteroylglutamic Acid and Reduced Folates: a Revised Hypothesis of the Primary Site of PteGlu Metabolism in Humans

Wright, Anthony JA, Finglas, Paul M, Dainty, Jack R., Wolfe, Caroline A., Hart, David J., Wright, Dawn M. and Gregory, Jesse F. (2005) Differential Kinetic Behavior and Distribution for Pteroylglutamic Acid and Reduced Folates: a Revised Hypothesis of the Primary Site of PteGlu Metabolism in Humans. The Journal of Nutrition, 135 (3). pp. 619-623. ISSN 0022-3166

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Abstract

Single 13C6-labeled doses of pteroylmonoglutamic acid (PteGlu: 634 nmol; n = 14), (6S-)5-formyltetrahydrofolic acid (431–569 nmol; n = 16), or [15N1–7]-intrinsically labeled spinach (mainly 5-methyltetrahydrofolate) (588 nmol; n = 14) were fed to fasting adult volunteers. Plasma-labeled 5-methyltetrahydrofolic acid responses were monitored for 8 h. There was a slower rate of increase in plasma-labeled 5-methyltetrahydrofolic acid and longer time to peak (171 ± 9 min; mean ± SEM) following an oral dose of [13C6]PteGlu than either [13C6]5-formyltetrahydrofolic acid (54 ± 10 min) or [15N1–7]spinach folate (60 ± 13 min) suggesting saturated metabolic capacity for the biotransformation of PteGlu. Mathematical modeling generated a significantly higher mean “apparent absorption” for 5-formyltetrahydrofolic acid (38%) and spinach folate (44%) than for PteGlu (24%). The high “relative absorption” of reduced folates to PteGlu was unexpected given that PteGlu itself, from 14C-tracer mass balance experiments, is almost completely absorbed. Although it is ubiquitously accepted that a physiological dose of PteGlu is reduced and methylated in the epithelial cells of the small intestine, and that essentially only 5-methyltetrahydrofolic acid is exported into the hepatic portal vein (HPV), as is the case for absorbed reduced 1-carbon-substituted folates, modeling indicated greater liver sequestration when PteGlu was used as the test dose, suggesting that PteGlu enters the HPV unaltered and that the liver is the primary site of initial metabolism. Because of the observed differential plasma response and the hypothesized difference in the site of initial metabolism, the historical use of PteGlu as a “reference folate” in studies of folate bioavailability is seriously questioned.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Chemical Sciences and Pharmacy
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Depositing User: Pure Connector
Date Deposited: 27 Feb 2018 15:30
Last Modified: 25 Jul 2019 00:53
URI: https://ueaeprints.uea.ac.uk/id/eprint/66389
DOI: 10.1093/jn/135.3.619

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