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J. Biol. Chem., Vol. 277, Issue 18, 15252-15260, May 3, 2002
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From the Vitamin C and flavonoids, polyphenols with
uncertain function, are abundant in fruits and vegetables. We
postulated that flavonoids have a novel regulatory action of delaying
or inhibiting absorption of vitamin C and glucose, which are
structurally similar. From six structural classes of flavonoids, at
least 12 compounds were chosen for studies. We investigated the effects
of selected flavonoids on the intestinal vitamin C transporter SVCT1(h)
by transfecting and overexpressing SVCT1(h) in Chinese hamster ovary
cells. Flavonoids reversibly inhibited vitamin C transport in
transfected cells with IC50 values of 10-50
µM, concentrations expected to have physiologic
consequences. The most potent inhibitor class was flavonols, of which
quercetin is most abundant in foods. Because Chinese hamster ovary
cells have endogenous vitamin C transport, we expressed SVCT1(h) in
Xenopus laevis oocytes to study the mechanism of transport
inhibition. Quercetin was a reversible and non-competitive inhibitor of
ascorbate transport; Ki 17.8 µM.
Quercetin was a potent non-competitive inhibitor of GLUT2 expressed in
Xenopus oocytes; Ki 22.8 µM. When diabetic rats were administered glucose with
quercetin, hyperglycemia was significantly decreased compared with
administration of glucose alone. Quercetin also significantly decreased
ascorbate absorption in normal rats given ascorbate plus quercetin
compared with rats given ascorbate alone. Quercetin was a specific
transport inhibitor, because it did not inhibit intestinal sugar
transporters GLUT5 and SGLT1 that were injected and expressed in
Xenopus oocytes. Quercetin inhibited but was not
transported by SVCT1(h). Considered together, these data show that
flavonoids modulate vitamin C and glucose transport by their respective
intestinal transporters and suggest a new function for flavonoids.
Flavonoid Inhibition of Sodium-dependent Vitamin C
Transporter 1 (SVCT1) and Glucose Transporter Isoform 2 (GLUT2),
Intestinal Transporters for Vitamin C and Glucose*
,,,,,¶
Molecular and Clinical Nutrition Section,
Digestive Diseases Branch, NIDDK, National Institutes of Health,
Bethesda, Maryland 20892-1372 and the § Phytonutrients
Laboratory, Beltsville Human Nutrition Research Center, U. S. Department of Agriculture, Beltsville, Maryland 20705
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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