Vitamin C transport and its role in the central nervous system

Redundant pathways mediate reduction of dehydroascorbic acid to ascorbic acid, including direct but slow nonenzymatic reduction by glutathione and enzymatic reduction by glutaredoxin, glutathione transferase omega 2, or thioredoxin reductase; the first two require glutathione.

“There are apparently redundant pathways mediating the reduction of dehydroascorbic acid to ascorbic acid. They include both direct but slow nonenzymatic reduction by glutathione and enzymatic by a couple of enzymes (e.g., glutaredoxin, glutathione transferase omega 2, or thioredoxin reductase). Of note is that the first two enzymes require glutathione for their activity [1,73].”

Physiologically high vitamin C levels (2-10 mM) are found in neurons and endocrine cells, particularly the adrenal and pituitary gland, apparently related to the synthesis of hormones and neuro-mediators.

“Physiologically high levels (2–10 mM) are found in neurons and endocrine cells (particularly, the adrenal and pituitary gland), which is apparently related to the synthesis of hormones and neuro-mediators described below [4,6,8,72,73].”

Vitamin C has little tendency to exit cells, likely due to its hydrophilic nature and negative charge at physiological pH.

“Vitamin C has little tendency to exit the cells likely due its hydrophilic nature and negative charge at a physiological pH [73].”

There are reports that vitamin C can pass through the blood-brain barrier in the form of dehydroascorbic acid through the glucose transporter GLUT1.

“There are also reports that vitamin C can pass through the blood-brain barrier in the form of dehydroascorbic acid through the glucose transporter GLUT1 [52,53,73].”

Dehydroascorbic acid has a half-life of about 6 minutes and is decomposed to 2,3-diketo-1-gulonic acid, losing vitamin C activity.

“It has a half-life of about 6 minutes. It is decomposed to 2,3-diketo-1-gulonic acid (Figure 4) and, in this way, it loses its activity of vitamin C [6,68,73].”

Vitamin C is crucial for the correct functions of the brain, and its levels in the central nervous system are less affected by vitamin C starving than other tissues.

“Vitamin C is apparently crucial for the correct functions of the brain and its levels in central nervous system are less affected by vitamin C starving than other tissues [73].”

The ascorbyl free radical is quite stable and can be detected in biological fluids at a concentration of 10 nM.

“The formed ascorbate (ascorbyl) free radical, also known as monodehydroascorbate or semidehydroascorbate, is quite stable and can be detected in biological fluids in a concentration of 10 nM [73,154].”