Metabolism and Excretion of Ascorbate

The major fate of ascorbic acid in human metabolism is excretion in the urine, either unchanged or as dehydroascorbate and diketogulonate. Both ascorbate and dehydroascorbate are filtered at the glomerulus, then reabsorbed, by a sodium-independent process. Reabsorbed dehydroascorbate is reduced to ascorbate in the kidneys. At plasma concentrations above about 85 ^mol per L, the renal transport systemis saturated, and ascorbate is excreted quantitatively with increasing intake.

Ascorbate catabolism is increased in subjects with iron overload, probably as a result of nonenzymic reactions with iron that is not protein-bound. The transferrin polymorphisms that are associated with susceptibility to iron overload result in higher vitamin C requirements for those subjects with high iron status (Kasvosve et al., 2002).

As shown in Figure 13.3, dehydroascorbate can undergo hydration to dike-togulonate, followed by decarboxylation to xylose, thus providing a route for entry into central carbohydrate metabolicpathways via the pentose phosphate pathway. This is the major metabolic fate of ascorbate in those species forwhich it is not vitamin and also in the guinea pig. However, oxidation to carbon dioxide is only a minor fate of ascorbate in humans. At intakes up to about 100 mg per day, less than 1% of the radioactivity from [14C]ascorbate is recovered as carbon dioxide. Although more 14CO2 is recovered from subjects receiving high intakes of the vitamin, this may be the result of bacterial metabolism of unabsorbed vitamin in the intestinal lumen (Kallner et al., 1985).

Although a number of studies have suggested that high intakes of ascorbate lead to synthesis and excretion of oxalate (Section, this seems to be the result of nonenzymic formation of oxalate in urine samples alter collection. There is no known pathway for oxalate synthesis from ascorbate.

Some species (but not primates) excrete ascorbate 2-sulfate, and in vitro ascorbic acid is a substrate for catechol O-methyltransferase, forming 2-methyl ascorbate.


Ascorbic acid has specific and well-defined roles in two classes of enzymes: the copper-containing hydroxylases (such as dopamine f-hydroxylase and peptidyl glycine hydroxylase) and the 2-oxoglutarate-linked iron-containing hydroxylases, of which the best studied are the proline and lysine hydroxylases involved in maturation of connective tissue (and other) proteins.

In addition to its coenzyme role in postsynthetic modification of collagen and other connective tissue proteins, there is evidence that vitamin C is involved in the regulation of connective tissue protein gene expression (Mahmoodian and Peterkofsky, 1999). The expression of a number of other genes has also been reported to be modulated by vitamin C, including

Ascorbic Acid Role Catecholemines
Figure 13.4. Synthesis of the catecholamines. Tyrosine hydroxylase, EC (see also Figure 10.10); aromatic amino acid decarboxylase, EC; and dopamine -hydroxylase, EC

cytochromes P450, and ubiquitin (Mizutani et al., 1997; Mori et al., 1997; Catani et al., 2001). The mechanism by which ascorbate affects gene expression is not clear, but may involve changes in the intracellular redox state (Lopez-Lluch et al., 2001).

Ascorbate also increases the activity of a number of other enzymes in vitro, although this is a nonspecific reducing action rather than reflecting any metabolic function of the vitamin. In addition, it has a number of relatively unspecific actions as a reducing agent and oxygen radical quencher. It is a potentially important antioxidant nutrient acting to recycle oxidized vitamin E. It also enhances absorption of inorganic iron and inhibits the formation of nitrosamines in the stomach.

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