*2.3. Recycling*

Following uptake across the intestinal epithelium, vitC is released into the bloodstream as ASC (>95% of vitC in human plasma is in the form of ASC [52,54]). Here, ASC is easily oxidized and the produced DHA rapidly taken up through GLUT1 transporters on the erythrocytes [55–57]. May and co-workers have demonstrated that DHA is rapidly recycled in erythrocytes predominantly via glutathione-dependent DHA reductases and with small contributions from reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent DHA reductases, such as thioredoxin reductase [58–66]. The resulting ASC may subsequently be released to the bloodstream [65]. During oxidizing conditions in the extracellular space, the generated DHA is absorbed by the surrounding cells and immediately reduced [45,55]. This reduction of DHA to ASC is either by chemical reduction by glutathione (GSH) [67] or by enzymatic reduction by glutaredoxin [68–70], protein disulfide isomerase (PDI) [69,70] or 3-α-hydroxysteroid dehydrogenase [71]. The mechanism by which DHA is reduced to ASC is a continuous process within the cellular cytoplasm, sustaining adequate levels of ASC to quench free radicals, such as superoxide, and/or reduce other antioxidants, such as vitamin E, maintaining redox homeostasis [56,72,73]. The rapid intracellular recycling of DHA also drives the efficient facilitated diffusion of DHA through the GLUTs, as the intracellular concentration is kept sufficiently low to allow DHA to move along a concentration gradient.
