Harrison Fiona E., May James M.
Free Radical Biology and Medicine, 2009
Abstract
Ascorbate (vitamin C) is a vital antioxidant molecule in the brain. However, it also has a number of other important functions, participating as a cofactor in several enzyme reactions, including catecholamine synthesis, collagen production, and regulation of HIF-1 alpha. Ascorbate is transported into the brain and neurons via the sodium-dependent vitamin C transporter 2 (SVCT2), which causes accumulation of ascorbate within cells against a concentration gradient. Dehydroascorbic acid, the oxidized form of ascorbate, is transported via glucose transporters of the GLUT family. Once in cells, it is rapidly reduced to ascorbate. The highest concentrations of ascorbate in the body are found in the brain and in neuroendocrine tissues such as adrenal, although the brain is the most difficult organ to deplete of ascorbate. Combined with regional asymmetry in ascorbate distribution within different brain areas, these facts suggest an important role for ascorbate in the brain. Ascorbate is proposed as a neuromodulator of glutamatergic, dopaminergic, cholinergic, and GABAergic transmission and related behaviors. Neurodegenerative diseases typically involve high levels of oxidative stress and thus ascorbate has been posited to have potential therapeutic roles against ischemic stroke, Alzheimer's disease, Parkinson's disease, and Huntington's disease.
Figures
Ascorbate metabolism. Chemical structures and reactions.
Ascorbate uptake and metabolism in the CNS. ASC, ascorbate; AFR, ascorbate free radical; DHA, dehydroascorbic acid; CSF, cerebrospinal fluid; X• oxidizing free radical species. Ascorbate enters the CSF either directly through the choroid plexus via the SVCT2 or possibly as DHA via GLUTs across the blood brain-barrier. Similarly ascorbate enters the neuron through the SVCT2 or as DHA via the GLUTs. AFR generated by X• dismutates to form DHA and ascorbate. Both the AFR and DHA are recycled back to ascorbate by cellular metabolism. Glial cells obtain ascorbate from the recycling of DHA that enters via GLUTs while neurons also have the SVCT2 for direct acquisition of ascorbate.
Ascorbate contents of plasma and various vertebrate organs.
| PMID: | 19162177 |
|---|---|
| PMCID (Free PMC Article): | PMC2649700 |
| DOI: | 10.1016/j.freeradbiomed.2008.12.018 |
| Category: | Brain / Mental Clarity |
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