Unlike the B vitamins, ascorbic acid has no coenzyme function, but acts as a cofactor in various reactions. Ascorbic acid acts as a reducing agent, and once oxidized to dehydroascorbic acid, it can be reduced back nonenzymatically by sulfhydryl agents, such as glutathione, or enzymatically by dehydroascorbate reductase.
Ascorbic acid is required by eukaryotic cells, but the capacity to synthesize ascorbic acid is absent in invertebrates, primates and most fishes. The missing step in the biosynthesis of ascorbic acid from glucose or galactose is the inability to convert l-gulonolactone to 2-keto-l-gulonolactone. The enzyme that catalyzes the conversion is l-gulonolactone oxidase (GLO).
Amphibians, reptiles and primitive birds are able to produce vitamin C in the kidney. During the evolution of the marsupials, the place of synthesis moved from the kidney to the more efficient liver, as in all other ascorbic-acid-synthesizing mammals (Moser, 1992). Like most invertebrates and fishes, evolved birds, guinea pigs, bats, monkeys, apes and man are incapable of synthesizing ascorbic acid. As always, there are exceptions, since some fish have been shown to be able to synthesize ascorbic acid (Yamamoto et al., 1978; Soliman et al., 1985; Moreau et al., 1996; MÊland and Waagb¯, 1998) .
GLO activity in the liver and (or) kidney has been found in mullet (Mugil cephalus), goldfish (Carrasius auratus), sturgeon (Acipenser transmontanus, A. baeri, A. fulvescens, A. ruthenus), African lungfish (Protopterus aethiopicus) and dogfish (Squalus acanthias) (Yamamoto et al., 1978; Soliman et al., 1985; Thomas et al., 1985; Tounata et al., 1995; Moreau et al., 1996, 1999; MÊland and Waagb¯, 1998). Various studies have suggested that carp (Cyprinus carpio) are able to synthesize ascorbic acid (Ikeda and Sato 1964, 1965; Yamamoto et al., 1978; Soliman et al., 1985; Sato et al., 1978; Reddy and Ramesh, 1996). Other studies have indicated that carp, at least in the larval stage, require ascorbic acid (Dabrowski et al., 1988; Dabrowski, 1991a). Most teleost fishes lack GLO activity (Dabrowski, 1990).
Vitamin C is required for a number of biologically important reactions (Hornig et al., 1984; Padh, 1990; Moser, 1992), although the requirement for ascorbic acid appears not to be absolute for some enzymes. Many other reducing agents, albeit at higher concentrations, can replace ascorbic acid at least to some extent, since partial enzyme activity for a few catalytic cycles can be detected in the absence of ascorbic acid (Hornig et al., 1984; Padh, 1990; Moser, 1992). Ascorbic acid has been found to be required for the following metabolic functions (Hornig et al., 1984; Padh, 1990; Moser, 1992):
- Normal collagen formation. Ascorbic acid is required through its action as a cofactor in the hydroxylation of proline and lysine residues in the biosynthesis of collagen (Ikeda et al., 1983). Ascorbate has also been found to increase the activities of both prolyl and lysyl hydroxylases. It also stimulates collagen biosynthesis in a manner unrelated to hydroxylation, thus playing a larger role in collagen formation.
- Due to the ease with which ascorbic acid can be oxidized and reversibly reduced, it is probable that it plays an important role in reactions involving electron transfer in the cell.
- Metabolic oxidation of certain amino acids, including tyrosine.
- Ascorbic acid has a role in metal ion metabolism due to its reducing and chelating properties. It can result in enhanced absorption of minerals from the diet and their mobilization and distribution throughout the body (Dabrowski and K–ck, 1989; Hsu and Shiau, 1999). Ascorbic acid has also been found to have a protective role against toxicity of water-borne heavy metals (Hilton, 1984).
- Carnitine is synthesized from lysine and methionine and is dependent on two hydroxylases (Miyasaki et al., 1995).
- Interrelationships of vitamin C to B vitamins are known, since tissue levels and urinary excretion of vitamin C are affected in animals with deficiencies of thiamin, riboflavin, pantothenic acid, folic acid and biotin (Duncan and Lovell, 1994b).
- Ascorbic acid is reported to have a stimulating effect on phagocytic activity of leukocytes, on functions of the reticuloendothelial system, and on formation of antibodies.
- Vitamin C has been demonstrated to be a natural inhibitor of nitrosamines, which are potent carcinogens.
- Synthesis of corticosteroids in adrenal glands may involve ascorbic acid-related hydroxylation steps.
- Ascorbic acid is found in up to tenfold concentrations in seminal fluid (as compared with serum levels). Decreasing levels have caused nonspecific sperm agglutination.
- Drug-metabolizing enzymes. Hepatic microsomal hydroxylation and demethylation systems are depressed by 50% in ascorbic acid-deficient guinea pigs.
- Normal behavior via brain neurotransmitters. Ascorbic acid-deficient fish have altered brain neurotransmitter levels and altered social and schooling behavior (Johnston et al., 1989; Koshio et al., 1997; Sakakura et al., 1998; Blom et al., 1999).
- Ascorbic acid activates phosphenolpyruvate carboxykinase or protects if from inactivation caused by oxidants (Maggini and Walter, 1997).
- Ascorbic acid is absorbed by a sodium-dependent transporter (Rose and Choi, 1990; Maffia et al., 1993).