The Biochemical Functions of Ascorbic Acid

Englard, Sasha; Seifter, Sam

doi:10.1146/annurev.nu.06.070186.002053

Cited by 492 publications

(257 citation statements)

References 82 publications

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“…(The order of intracellular substrate dissociation is assumed.) Each carrier state is identified by a number (1)(2)(3)(4)(5)(6)(7)(8) and by a prime denoting that the carrier is at the external face of the membrane or double prime indicating the internal face. A Na ϩ uniport pathway or "internal leak," also electroneutral (n H Na ϭ 1), is shown as step 2 3 7.…”

Section: Discussionmentioning

confidence: 99%

“…We present a transport model for SVCT1 that will provide a framework for investigating the impact of specific mutations and polymorphisms in SLC23A1 and help us better understand the contribution of SVCT1 to vitamin C metabolism in health and disease. cotransporters; sodium dependent; intestinal absorption; model simulation; renal reabsorption; Xenopus oocyte VITAMIN C (L-ascorbic acid) is an essential micronutrient that serves as an antioxidant scavenger of free radicals and as a cofactor in many enzymatic reactions (3,6,10,26,29). It cannot be synthesized in Homo sapiens and must be derived from the diet.…”

mentioning

confidence: 99%

“…VITAMIN C (L-ascorbic acid) is an essential micronutrient that serves as an antioxidant scavenger of free radicals and as a cofactor in many enzymatic reactions (3,6,10,26,29). It cannot be synthesized in Homo sapiens and must be derived from the diet.…”

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Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Mackenzie¹,

Illing²,

Hediger³

2008

American Journal of Physiology-Cell Physiology

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Mackenzie B, Illing AC, Hediger MA. Transport model of the human Na ϩ -coupled L-ascorbic acid (vitamin C) transporter SVCT1. Am J Physiol Cell Physiol 294: C451-C459, 2008. First published December 19, 2007 doi:10.1152/ajpcell.00439.2007.-Vitamin C (L-ascorbic acid) is an essential micronutrient that serves as an antioxidant and as a cofactor in many enzymatic reactions. Intestinal absorption and renal reabsorption of the vitamin is mediated by the epithelial apical L-ascorbic acid cotransporter SVCT1 (SLC23A1). We explored the molecular mechanisms of SVCT1-mediated L-ascorbic acid transport using radiotracer and voltage-clamp techniques in RNA-injected Xenopus oocytes. L-Ascorbic acid transport was saturable (K0.5 Ϸ 70 M), temperature dependent (Q10 Ϸ 5), and energized by the Na ϩ electrochemical potential gradient. We obtained a Na ϩ -L-ascorbic acid coupling ratio of 2:1 from simultaneous measurement of currents and fluxes. L-Ascorbic acid and Na ϩ saturation kinetics as a function of cosubstrate concentrations revealed a simultaneous transport mechanism in which binding is ordered Na ϩ , L-ascorbic acid, Na ϩ . In the absence of L-ascorbic acid, SVCT1 mediated pre-steady-state currents that decayed with time constants 3-15 ms. Transients were described by single Boltzmann distributions. At 100 mM Na ϩ , maximal charge translocation (Qmax) was Ϸ25 nC, around a midpoint (V0.5) at Ϫ9 mV, and with apparent valence ϷϪ1. Qmax was conserved upon progressive removal of Na ϩ , whereas V0.5 shifted to more hyperpolarized potentials. Model simulation predicted that the pre-steady-state current predominantly results from an ion-well effect on binding of the first Na ϩ partway within the membrane electric field. We present a transport model for SVCT1 that will provide a framework for investigating the impact of specific mutations and polymorphisms in SLC23A1 and help us better understand the contribution of SVCT1 to vitamin C metabolism in health and disease. cotransporters; sodium dependent; intestinal absorption; model simulation; renal reabsorption; Xenopus oocyte VITAMIN C (L-ascorbic acid) is an essential micronutrient that serves as an antioxidant scavenger of free radicals and as a cofactor in many enzymatic reactions (3,6,10,26,29). It cannot be synthesized in Homo sapiens and must be derived from the diet. Intestinal absorption and renal reabsorption of the vitamin is mediated by the epithelial Na ϩ -dependent Lascorbic acid cotransporter SVCT1 (reviewed in Refs. 32 and 35), the product of the SLC23A1 gene. Selective sorting of SVCT1 protein to the apical membrane has been demonstrated in cultured cell lines (Caco2 and MDCK) of intestinal and renal origin (2, 23).We and others previously demonstrated that human SVCT1 is a Na ϩ -dependent transporter that favors L-ascorbic acid over D-isoascorbic acid and that the oxidized form of vitamin C, dehydroascorbic acid, is excluded (5, 34). Here we explored its molecular mechanisms by testing the hypothesis that the Na ϩ dependence and rheogenicity of SVCT1 arise from...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Mackenzie¹,

Illing²,

Hediger³

2008

American Journal of Physiology-Cell Physiology

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“…It functions as an essential independent cellular antioxidant even in the presence of a vast excess of glutathione under oxidative challenge . It is a very potent scavenger of superoxide and other reactive oxygen species (Englard & Seifter, 1986). Of the two chemically distinct forms of vitamin C, only the reduced form, ascorbic acid, is present in human plasma, cells and tissues, and the cellular concentration of this vitamin can exceed the plasma level (60 mM) by several orders of magnitude (Guaiquil et al, 1997).…”

Section: Vitamin C and Vitamin C Transportersmentioning

confidence: 99%

Vitamin C and oxidative stress in the seminiferous epithelium

et al. 2011

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In this article, we focus on the fundamental role of vitamin C transporters for the normal delivery of vitamin C to germ cells in the adluminal compartment of seminiferous tubules. We argue that the redox status within spermatozoa or in semen is partly responsible for the etiology of infertility. In this context, antioxidant defence plays a critical role in male fertility. Vitamin C, a micronutrient required for a wide variety of metabolic functions, has long been associated with male reproduction. Two systems for vitamin C transport have been described in mammals. Facilitative hexose transporters (GLUTs), with 14 known isoforms to date, GLUT1-GLUT14, transport the oxidized form of vitamin C (dehydroascorbic acid) into the cells. Sodium ascorbic acid co-transporters (SVCTs), SVCT1 and SVCT2 transport the reduced form of vitamin C (ascorbic acid). Sertoli cells control germ cell proliferation and differentiation through cell-cell communication and form the blood-testis barrier. Because the blood-testis barrier limits direct access of molecules from the plasma into the adluminal compartment of the seminiferous tubule, one important question is the method by which germ cells obtain vitamin C. Some interesting results have thrown light on this matter. Expression of SVCT2 and some isoforms of GLUT transporters in the testis have previously been described. Our group has demonstrated that Sertoli cells express functionally active vitamin C transporters. Kinetic characteristics were described for both transport systems (SVCT and GLUT systems). Sertoli cells are able to transport both forms of vitamin C. These fi ndings are extremely relevant, because Sertoli cells may control the amount of vitamin C in the adluminal compartment, as well as regulating the availability of this metabolite throughout spermatogenesis.

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“…V itamin C (ascorbic acid) is required in the diets of humans and several other species that lack the terminal enzyme in its synthetic pathway, L-gulonolactone oxidase (1). It is involved in a number of vital functions within cells, including the hydroxylation reactions of collagen biosynthesis (2) and the facilitation of iron transport (3), as well as being one of the most important physiological antioxidants (4).…”

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confidence: 99%

Vitamin C Inhibits NF-κB Activation by TNF Via the Activation of p38 Mitogen-Activated Protein Kinase

Bowie

O’Neill

2000

The Journal of Immunology

289

163

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The transcription factor NF-κB is a central mediator of altered gene expression during inflammation, and is implicated in a number of pathologies, including cancer, atherosclerosis, and viral infection. We report in this study that vitamin C inhibits the activation of NF-κB by multiple stimuli, including IL-1 and TNF in the endothelial cell line ECV304 and in primary HUVECs. The induction of a NF-κB-dependent gene, IL-8, by TNF was also inhibited. The effect requires millimolar concentrations of vitamin C, which occur intracellularly in vivo, particularly during inflammation. Vitamin C was not toxic to cells, did not inhibit another inducible transcription factor, STAT1, and had no effect on the DNA binding of NF-κB. Inhibition by vitamin C was not simply an antioxidant effect, because redox-insensitive pathways to NF-κB were also blocked. Vitamin C was shown to block IL-1- and TNF-mediated degradation and phosphorylation of I-κBα (inhibitory protein that dissociates from NF-κB), due to inhibition of I-κB kinase (IKK) activation. Inhibition of TNF-driven IKK activation was mediated by p38 mitogen-activated protein kinase, because treatment of cells with vitamin C led to a rapid and sustained activation of p38, and the specific p38 inhibitor SB203580 reversed the inhibitory effect of vitamin C on IKK activity, I-κBα phosphorylation, and NF-κB activation. The results identify p38 as an intracellular target for high dose vitamin C.

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The Biochemical Functions of Ascorbic Acid

Cited by 492 publications

References 82 publications

Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Vitamin C and oxidative stress in the seminiferous epithelium

Vitamin C Inhibits NF-κB Activation by TNF Via the Activation of p38 Mitogen-Activated Protein Kinase

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The Biochemical Functions of Ascorbic Acid

Cited by 492 publications

References 82 publications

Transport model of the human Na+-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Transport model of the human Na+-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Vitamin C and oxidative stress in the seminiferous epithelium

Vitamin C Inhibits NF-κB Activation by TNF Via the Activation of p38 Mitogen-Activated Protein Kinase

Contact Info

Product

Resources

About

Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1