Vitamin C transport systems of mammalian cells
Open accessAbstract
Vitamin C is essential for many enzymatic reactions and also acts as a free radical scavenger. Specific non-overlapping transport proteins mediate the transport of the oxidized form of vitamin C, dehydroascorbic acid, and the reduced form, L-ascorbic acid, across biological membranes. Dehydroascorbic acid uptake is via the facilitated-diffusion glucose transporters, GLUT 1, 3 and 4, but under physiological conditions these transporters are unlikely to play a major role in the uptake of vitamin C due to the high concentrations of glucose that will effectively block influx. L-ascorbic acid enters cells via Na+-dependent systems, and two isoforms of these transporters (SVCT1 and SVCT2) have recently been cloned from humans and rats. Transport by both isoforms is stereospecific, with a pH optimum of approximately 7.5 and a Na+:ascorbic acid stoichiometry of 2:1. SVCT2 may exhibit a higher affinity for ascorbic acid than SVCT1 but with a lower maximum velocity. SVCT1 and SVCT2 are predicted to have 12 transmembrane domains, but they share no structural homology with other Na+ co-transporters. Potential sites for phosphorylation by protein kinase C exist on the cytoplasmic surface of both proteins, with an additional protein kinase A site in SVCT1. The two isoforms also differ in their tissue distribution: SVCT1 is present in epithelial tissues, whereas SVCT2 is present in most tissues with the exception of lung and skeletal muscle.
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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 [54]
The Functional characterization section reports an hSVCT1 Km of approximately 200 µM at pH 7.5, but the passages retrieved do not establish a 10–200 µM range. That section reports higher SVCT1 maximum transport velocity than SVCT2, and Tissue distribution notes SVCT1 expression in the small intestine; its proposed brush-border location remains a hypothesis, not a demonstrated capacity to absorb dietary vitamin C. Page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe plasma levels of dehydroascorbic acid are very low in healthy humans, while ascorbyl radical is undetectable.
“The plasma levels of dehydro-ascorbic acid are very low in healthy humans, while that of an ascorbyl radical are undetectable [6,53,54,62,67].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [54]
The ‘Uptake of dehydroascorbic acid’ section (page unavailable) says reduced vitamin C predominates in human plasma and gives circulating DHA levels of about 2–5 µM, supporting the claim that DHA levels are low. Our copy does not state that ascorbyl radical is undetectable in plasma. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSVCT1 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 [54]
Vitamin 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 [54]
Dehydroascorbic acid forms a bicyclic hemiketal that resembles glucose and has high affinity for glucose transporters GLUT1 and GLUT3 (GLUT4 can be involved, but GLUT2 and GLUT5 are not).
“Dehydroascorbic acid does not resemble glucose, but it forms bicyclic hemiketal (Figure 4A,B), which resembles glucose [74,75] and has high affinity for glucose transporters GLUT1 and GLUT3 (GLUT4 can be involved, but GLUT2 and GLUT5 are not) [54].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [54]
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References 45 · Cited by 255
Research works printed but not linked: 2
- Rose, R. C., 1986, Ascorbic acid transport in the mammalian kidney. American Journal of Physiology, 250, F627 ± F632.
- Zhuang, J., Prive, G. G., Werner, G. E., Ringler, P., Kabach, H. R. and Engel, A., 1999, Two-dimensional crystallization of Escher- ichia coli lactose permease. Journal of Structural Biology, 125, 63 ± 75.
- Authors
- Liang, W.-J., Johnson, D., & Jarvis, S. M.
- Affiliations
- University of Kent (GB)
- Venue
- Molecular Membrane Biology
- Publisher
- Informa UK Limited
- Published
- 2001-01
- Volume
- 18
- Issue
- 1
- Pages
- 87-95
- ISSN
- 0968-7688 (ISSN-L)
- 1464-5203
- OpenAlex
- W2113112540
- Cited by
- 255
- References
- 45
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 9 · 2020: 14 · 2019: 5 · 2018: 10 · 2017: 6 · 2016: 5 · 2015: 8 · 2014: 14 · 2013: 19 · 2012: 14
- FWCI
- 11.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Membrane Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- vitamin C transport, vitamin C, dehydroascorbic acid, sodium-dependent vitamin C transporters, SVCT1, SVCT2, GLUT transporters, facilitated diffusion, protein kinase C phosphorylation, protein kinase A, tissue distribution, epithelial cells, membrane transporters
- MeSH terms
- Amino Acid Sequence, Animals, Ascorbic Acid, Biological Transport, Cations, Cell Membrane, Cloning, Molecular, Dehydroascorbic Acid, Glucose, Hydrogen-Ion Concentration, Lung, Molecular Sequence Data, Phosphorylation, Phylogeny, Protein Kinase C, Proteins, Sodium, Time Factors, Tissue Distribution, Xenopus, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Muscle, Skeletal, COS Cells, Protein Isoforms, Symporters, Organic Anion Transporters, Sodium-Dependent, Sodium-Coupled Vitamin C Transporters
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