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

Abstract

Ever since Linus Pauling published his studies, the effects of vitamin C have been surrounded by contradictory results. This may be because its effects depend on a number of factors such as the redox state of the body, the dose used, and also on the tissue metabolism. This review deals with vitamin C pharmacokinetics and its participation in neurophysiological processes, as well as its role in the maintenance of redox balance. The distribution and the concentration of vitamin C in the organs depend on the ascorbate requirements of each and on the tissue distribution of sodium-dependent vitamin C transporter 1 and 2 (SVCT1 and SVCT2). This determines the specific distribution pattern of vitamin C in the body. Vitamin C is involved in the physiology of the nervous system, including the support and the structure of the neurons, the processes of differentiation, maturation, and neuronal survival; the synthesis of catecholamine, and the modulation of neurotransmission. This antioxidant interacts with self-recycling mechanisms, including its participation in the endogenous antioxidant system. We conclude that the pharmacokinetic properties of ascorbate are related to the redox state and its functions and effects in tissues.

Keywords: learning and memory processes; neurophysiology; oxidative stress; pharmacokinetics; vitamin C.

Figure 1

pH-dependent forms of vitamin C. At pH 7, close to plasma pH, the predominant form of vitamin C will be ascorbate monoanion, followed by ascorbic acid and, in very low concentrations, ascorbate dianion (0.005%); in an acidic pH, the predominant form will be ascorbic acid.

Figure 2

Vitamin C biosynthesis. The initial metabolite of both pathways is glucose, which through a sequence of reactions involving an energy expenditure by the cell, synthesizes L-ascorbic acid. 1, Glucose-6-phosphate isomerase; 2, Mannose-6-phosphate isomerase; 3, Phosphomannomutase; 4, GDPD-mannose pyrophosphorylase; 5, GDP-D-mannose-3,5-epimerase; 6, Phosphodiesterase; 7, Sugar phosphatase; 8, L-galactose dehydrogenase; 1′, Phosphoglucomutase; 2′, UDP-glucose pyrophosphorylase; 3′, UDP-glucose dehydrogenase; 4′, Glucuronate-1-phosphate uridylyltransferase and Glucurono kinase; 5′, Glucuronate reductase; 6′, Aldono-lactonase.

Figure 3

Influx and efflux mechanisms. (3.1) The type of SVCT transporter depends on the characteristics and requirements in each cell, SVCT2 being more frequent in tissues that require a constant supply of ascorbate, even under vitamin C deficiency conditions, while SVCT1 is more frequent in cells responsible for tissue distribution of ascorbate. (3.2) Ascorbate transportation into the enterocyte occurs through SVCT1, coupled to a Na+/K+ATPase. (3.3) Under conditions of restricted ascorbic acid intake, the supply of ascorbate to the cell is carried out through the SVCT2 located in the basolateral membrane, which is also coupled to a Na+/K+ATPase. (3.4) DHA is transported into the enterocyte via GLUT transporters. (3.5) Within the enterocyte, DHA is reduced to ascorbate, then exits the cell and spreads to the capillaries through the extracellular space.

Graphic 1

Effects of different doses of vitamin C on memory in redox balance and in oxidative stress. The retention latency was significantly decreased in the short term memory (STM) and in the long term memory (LTM) in the group that receive 0.7 ppm of ozone (O3) and in the group that receive 50 mg/kg of vitamin C (C50). Meanwhile, at any other doses greater than 50 mg/kg the retention latency were similar to the one of the control group. When any doses of vitamin C were added to the group exposed to ozone, the retention latency in STM and LTM was similar to that of the control group.

Graphic 2

Effects of different doses of vitamin C on lipid peroxidation levels in hippocampus in redox balance and in oxidative stress. The lipid peroxidation levels mainly increased in the group exposed to ozone (O3) and in the group that receive 50 mg/kg of vitamin C (C50). At any doses of vitamin C greater than 50 mg/kg the effect on lipid peroxidation levels was not as evident as in the C50 and O3 groups. In the groups that receive vitamin C and were exposed to ozone, vitamin C exerted an antioxidant effect (O3 + C50 and O3 + C100), except in the O3 + C200 group.