Ascorbic Acid and Its Role in Safeguarding Neurons: Updated Evidence

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Biochemistry and Biophysics (BAB) Volume 2 Issue 3, September 2014

Ascorbic Acid and Its Role in Safeguarding Neurons: Updated Evidence Y. Robert Li1-4*, Hong Zhu1, Yuebin Ke5, Zhenquan Jia4*, Hara P. Misra3, Emanuel J. Diliberto6 Campbell University School of Osteopathic Medicine, Buies Creek, NC 27506, USA

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Virginia Tech-Wake Forest University School of Biomedical Engineers and Sciences, Blacksburg, VA 24061, USA

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Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA 3

Department of Biology, University of North Carolina, Greensboro, NC 27412, USA

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Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.

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Department of Pharmaceutical Sciences, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC 27506, USA 6

* Corresponding author E-mail addresses: yli@campbell.edu (Y.R. Li), z_jia@uncg.edu (Z. Jia) Abstract Ascorbic acid, commonly known as vitamin C, is a watersoluble vitamin synthesized in plants as well as many animal species, but not in humans. Humans obtain ascorbic acid from dietary sources and via vitamin supplementation. Ascorbic acid possesses important biological functions, including serving as a cofactor for many enzymes, acting as an antioxidant, and participating in regulating cell growth, apoptosis, and signaling, which collectively contribute to its essentialness in maintaining and safeguarding the physiological homeostasis and the health of human body. This article summarizes recent evidence for ascorbic acid acting as a booster in neuron physiology and a protector in neuron degeneration. Keywords Ascorbic Acid; Antioxidant; Neuroprotection; Neurodegeneration

Overview Ascorbic acid, also known as ascorbate or vitamin C, is a water-soluble molecule synthesized endogenously in animals except humans, monkeys, guinea pigs, and several other animal species (Bruno et al. , 2006). Humans lost this capability because of a series of inactivating mutations of the gene encoding gulonolactone oxidase (GULO), a key enzyme in ascorbic acid biosynthesis. Humans normally acquire ascorbic acid from dietary sources through an active substrate-saturable transport mechanism. Dietary sources of ascorbic acid are mainly from vegetables and fruits, including Brussels sprouts, broccoli, bell peppers, lettuce, tomatoes, citrus fruits, strawberries,

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papayas, and mangoes. Another source is ascorbic acid supplement. Oral ascorbic acid intake produces plasma concentrations that are tightly controlled; once its oral intake exceeds 200 mg daily, it is difficult to further increase plasma concentration. The maximal plasma concentration attainable by oral intake of ascorbic acid has been estimated to be approximately 200 micromolar though the physiological plasma concentrations in healthy humans range from 40 to 100 micromolar. In contrast, intravenous injection of large doses of ascorbic acid produces millimolar concentrations of plasma ascorbic acid (Padayatty et al. , 2004). Under physiological conditions, intracellular levels of ascorbic acid are in the millimolar range. This is due to selective intracellular accumulation via ascorbic acid transport system present in the plasma membrane (Wilson, 2005). The high intracellular concentrations of ascorbic acid in mammalian tissues suggest its essential roles in maintaining physiological homeostasis and proper functions of organs and systems. In this article, we first examine the novel biochemical properties and functions of ascorbic acid, and then discuss recent research evidence supporting its multi-tasking functions in safeguarding neurons and protecting against neurodegenerative disorders, a major contributor to the global burden of disease. Ascorbic Acid as a Multi-tasking Molecule Since its isolation from adrenal glands by Albert Szent-Gyรถrgyi in 1928 (Carpenter, 2012), ascorbic acid


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