Vitamin C in Health and Disease: Its Role in the Metabolism of Cells and Redox State in the Brain (original) (raw)

Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2

Free Radical Biology and Medicine, 2009

Ascorbate (vitamin C) is a vital antioxidant molecule in the brain. However, it also has a number of other important functions, participating as a co-factor in several enzyme reactions including catecholamine synthesis, collagen production and regulation of HIF-1α. 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 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 Huntingdon's disease.

Neurobiology of vitamin C: Expanding the focus from antioxidant to endogenous neuromodulator

Pharmacological Research, 2019

Ascorbic acid (AA) is a water-soluble vitamin (C) found in all bodily organs. Most mammals synthesize it, humans are required to eat it, but all mammals need it for healthy functioning. AA reaches its highest concentration in the brain where both neurons and glia rely on tightly regulated uptake from blood via the glucose transport system and sodiumcoupled active transport to accumulate and maintain AA at millimolar levels. As a prototype antioxidant, AA is not only neuroprotective, but also functions as a cofactor in redox-coupled reactions essential for the synthesis of neurotransmitters (e.g., dopamine and norepinephrine) and paracrine lipid mediators (e.g., epoxiecoisatrienoic acids) as well as the epigenetic regulation of DNA. Although redox capacity led to the promotion of AA in high doses as potential treatment for various neuropathological and psychiatric conditions, ample evidence has not supported this therapeutic strategy. Here, we focus on some long-neglected aspects of AA neurobiology, including its modulatory role in synaptic transmission as demonstrated

Vitamin C: update on physiology and pharmacology

British Journal of Pharmacology, 2009

Although ascorbic acid is an important water-soluble antioxidant and enzyme cofactor in plants and animals, humans and some other species do not synthesize ascorbate due to the lack of the enzyme catalyzing the final step of the biosynthetic pathway, and for them it has become a vitamin. This review focuses on the role of ascorbate in various hydroxylation reactions and in the redox homeostasis of subcellular compartments including mitochondria and endoplasmic reticulum. Recently discovered functions of ascorbate in nucleic acid and histone dealkylation and proteoglycan deglycanation are also summarized. These new findings might delineate a role for ascorbate in the modulation of both pro-and anti-carcinogenic mechanisms. Recent advances and perspectives in therapeutic applications are also reviewed. On the basis of new and earlier observations, the advantages of the lost ability to synthesize ascorbate are pondered. The increasing knowledge of the functions of ascorbate and of its molecular sites of action can mechanistically substantiate a place for ascorbate in the treatment of various diseases.

Vitamin C physiology: the known and the unknown andGoldilocks

2016

Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium-dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids. Plasma and tissue vitamin C concentrations are dependent on amount consumed, bioavailability, renal excretion, and utilization. To be biologically meaningful or to be clinically relevant, in vitro and in vivo studies of vitamin C actions have to take into account physiologic concentrations of the vitamin. In this paper, we review vitamin C physiology; the many phenomena involving vitamin C where new knowledge has accrued or where understanding remains limited; raise questions about the vitamin that remain to be answered; and explore...

Vitamin C: the known and the unknown and Goldilocks

Oral Diseases, 2016

Vitamin C distribution and retention in the mouse brain

Brain Research, 2010

Vitamin C (VC) is a crucial antioxidant in the brain. To assess whether different brain regions vary in their sensitivity to oxidative stress induced by VC depletion, we used the gulonolactone oxidase (gulo) knockout mouse. This mouse, like humans, cannot synthesize VC and thus its tissue VC levels can be varied by dietary VC intake. Gulo knockout mice were fed drinking water containing standard (0.33 g/L), low (0.033 g/L) or zero (0 g/L) VC supplementation levels. After 4 weeks, mice were sacrificed and different brain regions removed for assay of VC and malondialdehyde, a marker of lipid peroxidation. Compared to age-matched wild-type controls, the cerebellum, olfactory bulbs and frontal cortex had the highest VC content, whereas the pons and spinal chord had the lowest. However, in mice that did not receive VC, area differences were no longer significant as all values trended towards zero. Malondialdehyde increased in the cortex as VC supplementation was decreased. The same changes were not observed in the cerebellum or pons, suggesting that cortex is more susceptible to oxidative damage from low VC. These results suggest enhanced susceptibility of the cortex to oxidative stress induced by low VC compared to other brain regions.

Role of Vitamin C (Ascorbic Acid) on Human Health- a Review

Vitamin C, also known as ascorbic acid, abounds in nature and is highly labile. It is a water-soluble vitamin that is lost in large amounts during food processing. It is a vitamin whose prescribed requirement across cultures is not uniform. For example , the prescribed requirement of vitamin C in Great Britain is 30mg/day, while in the U.S.A., it is 60mg/day and 100mg/day in Japan. These variations are unusual and point to the need for further research to establish the acceptable RDAs for diverse populations. The RDA for vitamin C should be more than the amount needed to prevent the occurrence of disease. Vitamin C plays significant functions in the body that enhance its role in the health status of the human body. The biochemical functions of vitamin C include: stimulation of certain enzymes, collagen biosynthesis, hormonal activation, antioxidant, detoxification of histamine, phagocytic functions of leukocytes, formation of nitrosamine, and proline hydroxylation amongst others. Th...

Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters

Journal of Clinical Investigation, 1997

Vitamin C concentrations in the brain exceed those in blood by 10-fold. In both tissues, the vitamin is present primarily in the reduced form, ascorbic acid. We identified the chemical form of vitamin C that readily crosses the blood-brain barrier, and the mechanism of this process. Ascorbic acid was not able to cross the blood-brain barrier in our studies. In contrast, the oxidized form of vitamin C, dehydroascorbic acid (oxidized ascorbic acid), readily entered the brain and was retained in the brain tissue in the form of ascorbic acid. Transport of dehydroascorbic acid into the brain was inhibited by D -glucose, but not by L -glucose. The facilitative glucose transporter, GLUT1, is expressed on endothelial cells at the blood-brain barrier, and is responsible for glucose entry into the brain. This study provides evidence showing that GLUT1 also transports dehydroascorbic acid into the brain. The findings define the transport of dehydroascorbic acid by GLUT1 as a mechanism by which the brain acquires vitamin C, and point to the oxidation of ascorbic acid as a potentially important regulatory step in accumulation of the vitamin by the brain. These results have implications for increasing antioxidant potential in the central nervous system. (

Vitamin C—Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination

Nutrients

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins. The role of vitamin C is well demonstrated by miscellaneous symptoms of its absence—scurvy. The only clinically well-documented indication for vitamin C is scurvy. The effects of vitamin C administration on cancer, cardiovascular diseases, and infections are rather minor or even debatable in the general population. Vitamin C is r...

Vitamin C in Health and Disease: Its Role in the Metabolism of Cells and Redox State in the Brain (original) (raw)

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