Vitamin-C Transport
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Vitamin-C Transport

Vitamin-C (Ascorbate or Ascorbic Acid) is an essential water-soluble Vitamin, well known for its antiscorbutic and antioxidant functions in humans. Vitamin-C was first identified by virtue of the essential role it plays in Collagen modification, preventing the nutritional deficiency Scurvy. Vitamin-C acts as a cofactor for the P4H (Prolyl Hydroxylase) enzymes, which post-translationally modify Collagen and thereby increase the strength and elasticity of tissues. Vitamin-C reduces the metal ion prosthetic groups of many enzymes, thereby maintaining the activity of enzymes. The fact that prevention of Scurvy through modification of Collagen is the most obvious role for Vitamin-C; it is not necessarily the only role of Vitamin-C (Ref.1). Collagen modification depends on the Vitamin-C concentration within the tissues and requires regular dietary intake and active transport of the Vitamin within tissues. Vitamin-C/Ascorbate absorbed from nutrients enters the intestinal epithelium and are accumulated in the blood plasma through Ascorbate transporters. SVCTs (Sodium-Dependent Vitamin-C Transporters) are Ascorbate transporters for Vitamin-C import into cells. These transporters specifically transport reduced L-Ascorbic Acid against a concentration gradient using the intracellular Sodium gradient to drive Ascorbate transport. SVCTs are expressed in the cells of spleen, brain, eye, pancreas, testis, ovary, adrenal gland, lung etc (Ref.2 & 3).

Vitamin-C imported from the intestine is present in plasma, almost exclusively in the reduced form as AFR (Ascorbate Free Radical) and DHA (Dehydroascorbate) and is also transported to tissues to play a variety of roles. Ascorbate donates either one or two electrons in redox reactions. At physiological pH, more than 99 percent of Ascorbate is in the monoanion form. Loss of the first electron results in the formation of AFR. The AFR, although a stronger reducing agent than Ascorbate, is stabilized by resonance on the three-ring oxygens and is not very reactive. Mild oxidants such as Fe3+(CN)6 (Ferricyanide) remove a second electron and convert the AFR to DHA and itself gets reduced to Fe2+(CN)6 (Ferrocyanide). Ferricyanide reduction is associated with increased intracellular ATP generation. PMOR (Plasma Membrane Oxidoreductases), a multienzyme complex that includes NADPH- Ferricyanide Reductase and NADPH Oxidase along with Cytochrome-B5 Reductases play a vital role in the conversion of AFR to DHA. Despite the term ‘acid’ in its common name, DHA is uncharged at physiological pH. This lack of charge increases its ability to diffuse across the plasma membrane and it also gets transported to the cytoplasm through GLUTs (Glucose Transporters). GLUTs do not transport Ascorbate in vivo (Ref.3). DHA is unstable at physiological pH and unless reduced back to Ascorbate, it undergoes irreversible ring opening to form 2,3-Diketo-1-Gulonic Acid. Once inside cells, DHA is very rapidly reduced to Ascorbate, either directly by Glutathione or in reactions catalyzed by TxnRd (Thioredoxin Reductase) or Glrx (Glutaredoxin). NADH-dependent mechanisms may also contribute to this mechanism. Inside the cells Vitamin-C activates cytoplasmic P4H enzymes in order to facilitate strengthening of tissues (Ref.4).

As an electron donor and a redoxactive compound, Vitamin-C participates as a cofactor in many enzymatic reactions, including the hydroxylation of Collagen, synthesis of Carnitine, metabolism of Tyrosine, Nitric Oxide synthesis, Catecholamine synthesis and Peptide Amidation. As a powerful antioxidant Vitamin-C participates in many non-enzymatic reactions preventing oxidation of low-density lipoproteins to alleviate pathological conditions. Vitamin C has been called “A Cure for Miracles” and sub-clinical deficiency of the Vitamin is of common occurrence in humans (Ref.1). The clinical state that arises from dietary deficiency of Vitamin-C is, Scurvy and is of the most serious diseases affecting teenagers. Apart from its essential role in human nutrition, Vitamin-C has occupied an important place in preventive medicine to safeguard health from several pathological conditions, such as cancer, infections, viral respiratory illnesses, common cold, and above all, cardiovascular diseases (Ref.5).