Abstract
Intestinal vitamin C (Asc) absorption was believed to be mediated by the Na(+)-dependent ascorbic acid transporter SVCT1. However, Asc transport across the intestines of SVCT1 knock-out mice is normal indicating that alternative ascorbic acid transport mechanisms exist. To investigate these mechanisms, rodents were gavaged with Asc or its oxidized form dehydroascorbic acid (DHA), and plasma Asc concentrations were measured. Asc concentrations doubled following DHA but not Asc gavage. We hypothesized that the transporters responsible were facilitated glucose transporters (GLUTs). Using Xenopus oocyte expression, we investigated whether facilitative glucose transporters GLUT2 and GLUT5-12 transported DHA. Only GLUT2 and GLUT8, known to be expressed in intestines, transported DHA with apparent transport affinities (Km) of 2.33 and 3.23 mm and maximal transport rates (Vmax) of 25.9 and 10.1 pmol/min/oocyte, respectively. Maximal rates for DHA transport mediated by GLUT2 and GLUT8 in oocytes were lower than maximal rates for 2-deoxy-d-glucose (Vmax of 224 and 32 pmol/min/oocyte for GLUT2 and GLUT8, respectively) and fructose (Vmax of 406 and 116 pmol/min/oocyte for GLUT2 and GLUT8, respectively). These findings may be explained by differences in the exofacial binding of substrates, as shown by inhibition studies with ethylidine glucose. DHA transport activity in GLUT2- and GLUT8-expressing oocytes was inhibited by glucose, fructose, and by the flavonoids phloretin and quercetin. These studies indicate intestinal DHA transport may be mediated by the facilitative sugar transporters GLUT2 and GLUT8. Furthermore, dietary sugars and flavonoids in fruits and vegetables may modulate Asc bioavailability via inhibition of small intestinal GLUT2 and GLUT8.
Highlights
The molecular identity of the intestinal vitamin C transporters is incomplete
Previous studies [16] had shown that mutating the N-terminal di-leucine motif in rat GLUT8 to a di-alanine motif was necessary for plasma membrane expression and functional characterization in oocytes; we studied the transport properties of selected human wild type and mutant glucose transporters (GLUTs) in injected oocytes. mRNA encoding the individual isoforms were injected into oocytes, and 3–5 days post-injection, oocytes expressing putative GLUTs were incubated with 300 M [14C]dehydroascorbic acid (DHA) for 10 min, and radiolabeled uptake was assessed
On a mole for mole basis, 2-DG and DHA uptake was similar in GLUT1-expressing oocytes, whereas for GLUT2-expressing oocytes 2-DG uptake was ϳ30fold greater than DHA, and for GLUT8 expressing oocytes 2-DG uptake was ϳ5-fold greater than DHA
Summary
The molecular identity of the intestinal vitamin C transporters is incomplete. Results: Facilitative sugar transporters, GLUT2 and GLUT8, transport dehydroascorbic acid, the oxidized form of vitamin C. Intestinal vitamin C (Asc) absorption was believed to be mediated by the Na؉-dependent ascorbic acid transporter SVCT1. Asc transport across the intestines of SVCT1 knockout mice is normal indicating that alternative ascorbic acid transport mechanisms exist To investigate these mechanisms, rodents were gavaged with Asc or its oxidized form dehydroascorbic acid (DHA), and plasma Asc concentrations were measured. DHA transport activity in GLUT2- and GLUT8-expressing oocytes was inhibited by glucose, fructose, and by the flavonoids phloretin and quercetin These studies indicate intestinal DHA transport may be mediated by the facilitative sugar transporters GLUT2 and GLUT8. Whether Asc alone or DHA was the substrate for tissue accumulation was addressed first by creating knock-out mice lacking the generally distributed tissue transporter SVCT2. When Asc was administered orally by gavage to SVCT1 knock-out mice, blood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
