Vitamin C transport systems of mammalian cells

Abstract

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.

Decreased Tissue Accumulation of 6-Deoxy-6-[18F]fluoro-L-ascorbic Acid in Glutathione-Deficient Rats Induced by Administration of Diethyl Maleate

“…1) as a positron-labeled analog of ascorbic acid for studying oxidative damages in vivo by positron emission tomography (PET). Tissue distribution studies in normal rats or tumor-bearing mice demonstrated that the uptake and distribution pattern of 18 F-DFA has a remarkable resemblance to that reported for [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]ascorbate, with preferential uptake in the adrenal glands and slow brain uptake kinetics. [3][4][5] Recently, Monnier et al used DFA for studying the mechanism in experimental diabetes with 19 F-NMR spectroscopy, showing that DFA is a very powerful tool for the clarification of ascorbate homeostasis and catabolism in vivo.…”

Genome-wide analysis shows association of epigenetic changes in regulators of Rab and Rho GTPases with spinal muscular atrophy severity

“…51 This transporter provides high ascorbate concentration in most tissues. In the CNS, ascorbate has several functions including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation and protection against glutamate toxicity.…”

Hyperpolarized 13 C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

“…DHA is maintained at much lower intracellular concentrations than Vitamin C, but has a number of unique properties that set it apart. While the Na þ -dependent cotransporters SVCT1 and SVCT2 transport Vitamin C, DHA is transported by facilitated diffusion via the glucose transporters GLUT1, GLUT2, and GLUT4, with rapid reduction of DHA to Vitamin C occurring within the cell (22). The transport, and structural properties of DHA make it an excellent candidate for in vivo metabolic studies using hyperpolarized 13 C MRSI.…”