Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2
Open accessAbstract
Two sodium-dependent vitamin C transporters, hSVCT1 and hSVCT2, were cloned from a human kidney cDNA library. hSVCT1 had a 1797 bp open reading frame encoding a 598 amino acid polypeptide. The 1953 bp open reading frame of hSVCT2 encoded a 650 amino acid polypeptide. Using a Xenopus laevis oocyte expression system, both transporters were functionally expressed. By Eadie-Hofstee transformation the apparent K(m) of hSVCT1 for ascorbate was 252.0 microM and of hSVCT2 for ascorbate was 21.3 microM. Both transporters were sodium-dependent and did not transport dehydroascorbic acid. Incubation of oocytes expressing either transporter with phorbol 12-myristate 13-acetate (PMA) inhibited ascorbate transport activity. Availability of the human transporter clones may facilitate new strategies for determining vitamin C intake.
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The Michaelis constant Km for vitamin C transport by SVCT1 was reported to be in a wide range from 10 to 200 μM, suggesting a large capacity to absorb dietary vitamin C.
“The Michaelis constant Km, i.e., the concentration of vitamin C transported by half of the maximal transport velocity, was reported to be in a wide range from 10 to 200 µM, suggesting a large capacity to absorb dietary vitamin C.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [51]
Section 3.3 (Ascorbate transport kinetics) reports hSVCT1 Km values of 233.8 and 252.0 µM, both outside the claimed 10–200 µM range. The Discussion proposes a role for hSVCT1 in intestinal vitamin C absorption, but does not establish the claimed large absorptive capacity. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredVitamin C is efficiently and saturably reabsorbed from the urinary tract, and SVCT1 plays an important role, as documented by knockout Slc23a1−/− mice with an 18-fold higher ascorbate excretion.
“Vitamin C is efficiently and saturably reabsorbed from the urinary tract, and SVCT1 plays an important role, as documented by knockout Slc23a1−/− mice with an 18-fold higher ascorbate excretion [51,80,81].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [51]
The Discussion proposes that hSVCT1 may contribute to renal tubular reabsorption of vitamin C, and the Ascorbate transport kinetics section reports saturable uptake in oocytes expressing hSVCT1. Neither passage establishes efficient, saturable reabsorption in the urinary tract, and this paper does not report Slc23a1 knockout mice or an 18-fold increase in ascorbate excretion. (LLM, conf=0.90)
Experimental — accuracy not yet measuredVitamin C is taken up by cells via SVCT2.
“Vitamin C is taken up by the cells via SVCT2 (SLC23A2, Figure 2C), which is a close analogue of SVCT1 with which it shares 65% sequence homology.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [51]
SVCT1 activity is highest at a neutral pH and drops markedly with increasing acidity.
“Its activity is highest at a neutral pH. It drops markedly with increasing acidity [51,52,53,54].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [51]
Section 2.4 (page unavailable) says ascorbate transport was measured in a solution at pH 7.8, but reports no measurements at other pH values. The functional-expression and transport-kinetics results likewise do not compare neutral and acidic conditions, so our copy cannot establish where SVCT1 activity is highest or whether acidity markedly reduces it. (LLM, conf=0.76)
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- Authors
- Daruwala, R., Song, J., Koh, W. S., Rumsey, S. C., & Levine, M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Levine, Mark
- ORCID
- Levine, Mark
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1999-11
- Volume
- 460
- Issue
- 3
- Pages
- 480-484
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2079405203
- Cited by
- 272
- References
- 19
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 10 · 2022: 1 · 2021: 15 · 2020: 10 · 2019: 3 · 2018: 11 · 2017: 6 · 2016: 8 · 2015: 9 · 2014: 6 · 2013: 17 · 2012: 9
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- sodium-dependent vitamin C transporters, ascorbate transport, vitamin C, dehydroascorbic acid, phorbol myristate acetate, transporter inhibition, kidney, oocyte expression, Michaelis constant, vitamin C intake
- MeSH terms
- Amino Acid Sequence, Animals, Ascorbic Acid, Base Sequence, Biological Transport, Carrier Proteins, Cloning, Molecular, Bucladesine, Female, Humans, Molecular Sequence Data, Oocytes, Proteins, Sodium, Tetradecanoylphorbol Acetate, Protein Biosynthesis, Xenopus laevis, Symporters, Organic Anion Transporters, Sodium-Dependent, Sodium-Coupled Vitamin C Transporters
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