Vitamin C transport systems of mammalian cells.
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.
Liang
W J
WJ
Research School of Biosciences, University of Kent, Canterbury, UK.
Johnson
D
D
Jarvis
S M
SM
D000595:Amino Acid Sequence; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport; D019556:COS Cells; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D003683:Dehydroascorbic Acid / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism; D010766:Phosphorylation; D010802:Phylogeny; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D013997:Time Factors; D014018:Tissue Distribution; D014981:Xenopus
D002412:Cations; D029363:Organic Anion Transporters, Sodium-Dependent; D020033:Protein Isoforms; D011506:Proteins; C555162:SLC23A1 protein, human; C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D012964:Sodium; D011493:Protein Kinase C; D005947:Glucose; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid