HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rumsey, S. C. Articles by Levine, M. Search for Related Content PubMed PubMed Citation Articles by Rumsey, S. C. Articles by Levine, M. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 33, 23215-23222, August 13, 1999

Specificity of Ascorbate Analogs for Ascorbate Transport
SYNTHESIS AND DETECTION OF [¹²⁵I]6-DEOXY-6-IODO-L-ASCORBIC ACID AND CHARACTERIZATION OF ITS ASCORBATE-SPECIFIC TRANSPORT PROPERTIES

Steven C. Rumsey, Richard W. Welch, H. Martin Garraffo^§, Ping Ge^§, Shou-Fu Lu^§, Arthur T. Crossman^§, Kenneth L. Kirk^§, and Mark Levine

From the  Molecular and Clinical Nutrition Section, Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1372 and the ^§ Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0820

Cellular ascorbic acid accumulation occurs in vitro by two distinct mechanisms: transport of ascorbate itself or transport and subsequent intracellular reduction of its oxidized product, dehydroascorbic acid. It is unclear which mechanism predominates in vivo. An easily detectable compound resembling ascorbate but not dehydroascorbic acid could be a powerful tool to distinguish the two transport activities. To identify compounds, 21 ascorbate analogs were tested for inhibition of ascorbate or dehydroascorbic acid transport in human fibroblasts. The most effective analogs, competitive inhibitors of ascorbate transport with K_i values of 3 µM, were 6-deoxy-6-bromo-, 6-deoxy-6-chloro-, and 6-deoxy-6-iodo-L-ascorbate. No analog inhibited dehydroascorbic acid transport. Using substitution chemistry, [¹²⁵I]6-deoxy-6-iodo-L-ascorbate (1.4 × 10⁴ mCi/mmol) was synthesized. HPLC detection methods were developed for radiolabeled and nonradiolabeled compounds, and transport kinetics of both compounds were characterized. Transport was sodium-dependent, inhibited by excess ascorbate, and similar to that of ascorbate. Transport of oxidized ascorbate and oxidized 6-deoxy-6-iodo-L-ascorbate was investigated using Xenopus laevis oocytes expressing glucose transporter isoform GLUT1 or GLUT3. Oxidation of ascorbate or its analog in media increased uptake of ascorbate in oocytes by 6-13-fold compared with control but not that of 6-deoxy-6-iodo-L-ascorbate. Therefore, 6-deoxy-6-iodo-L-ascorbate, although an effective inhibitor of ascorbate transport, either in its reduced or oxidized form was not a substrate for dehydroascorbic acid transport. Thus, radiolabeled and nonradiolabeled 6-deoxy-6-iodo-L-ascorbate provide a new means for discriminating dehydroascorbic acid and ascorbate transport in ascorbate recycling.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				H. C. Erichsen, S. A. M. Engel, P. K. Eck, R. Welch, M. Yeager, M. Levine, A. M. Siega-Riz, A. F. Olshan, and S. J. Chanock Genetic Variation in the Sodium-dependent Vitamin C Transporters, SLC23A1, and SLC23A2 and Risk for Preterm Delivery Am. J. Epidemiol., February 1, 2006; 163(3): 245 - 254. [Abstract] [Full Text] [PDF]

				C. P. Corpe, J.-H. Lee, O. Kwon, P. Eck, J. Narayanan, K. L. Kirk, and M. Levine 6-Bromo-6-deoxy-L-ascorbic Acid: AN ASCORBATE ANALOG SPECIFIC FOR Na+-DEPENDENT VITAMIN C TRANSPORTER BUT NOT GLUCOSE TRANSPORTER PATHWAYS J. Biol. Chem., February 18, 2005; 280(7): 5211 - 5220. [Abstract] [Full Text] [PDF]

				M. Satake, B. Dmochowska, Y. Nishikawa, J. Madaj, J. Xue, Z. Guo, D. V. Reddy, P. L. Rinaldi, and V. M. Monnier Vitamin C Metabolomic Mapping in the Lens with 6-Deoxy-6-fluoro-ascorbic Acid and High-Resolution 19F-NMR Spectroscopy Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 2047 - 2058. [Abstract] [Full Text] [PDF]

				J. B. Cross, R. P. Currier, D. J. Torraco, L. A. Vanderberg, G. L. Wagner, and P. D. Gladen Killing of Bacillus Spores by Aqueous Dissolved Oxygen, Ascorbic Acid, and Copper Ions Appl. Envir. Microbiol., April 1, 2003; 69(4): 2245 - 2252. [Abstract] [Full Text] [PDF]

				N. P. Maulen, E. A. Henriquez, S. Kempe, J. G. Carcamo, A. Schmid-Kotsas, M. Bachem, A. Grunert, M. E. Bustamante, F. Nualart, and J. C. Vera Up-regulation and Polarized Expression of the Sodium-Ascorbic Acid Transporter SVCT1 in Post-confluent Differentiated CaCo-2 Cells J. Biol. Chem., March 7, 2003; 278(11): 9035 - 9041. [Abstract] [Full Text] [PDF]

				H. C. Erichsen, P. Eck, M. Levine, and S. Chanock Characterization of the Genomic Structure of the Human Vitamin C Transporter SVCT1 (SLC23A2) J. Nutr., October 1, 2001; 131(10): 2623 - 2627. [Abstract] [Full Text] [PDF]

				M. Levine, Y. Wang, S. J. Padayatty, and J. Morrow A new recommended dietary allowance of vitamin C for healthy young women PNAS, August 14, 2001; 98(17): 9842 - 9846. [Abstract] [Full Text] [PDF]

				C. A STRATAKIS, S. E TAYMANS, R. DARUWALA, J. SONG, and M. LEVINE Mapping of the human genes (SLC23A2 and SLC23A1) coding for vitamin C transporters 1 and 2 (SVCT1 and SVCT2) to 5q23 and 20p12, respectively J. Med. Genet., September 1, 2000; 37(9): 20e - 20. [Full Text]