Animals, ascorbic acid biosynthesis

L-Ascorbic acid biosynthesis in plants and animals as well as the chemical synthesis starts from D-glucose. The vitamin and its main derivatives, sodium ascorbate, calcium ascorbate, and ascorbyl palmitate, are officially recognized by regulatory agencies and included in compendia such as the United S fates Pharmacopeia/National Formula (USP/NF) and the Food Chemicals Codex (FCC). 

In all plants and most animals, L-ascorbic acid is produced from D-glucose (4) and D-galactose (26). Ascorbic acid biosynthesis in animals starts with D-glucose (4). In plants, where the biosynthesis is more compHcated, there are two postulated biosynthetic pathways for the conversion of D-glucose or D-galactose to ascorbic acid. 

The new knowledge of ascorbic acid biosynthesis and degradation has called attention to the variable metabolism of ascorbic acid, induced by drugs of various kinds, and to the complementary effects on the metabolism of drugs, produced by ascorbic acid. Changes of this sort may eventually explain many puzzling features of the metabolism of ascorbic acid in scorbutic animals in different physiological states. 

Nishikimi, M., Noguchi, E., and Yagi, K., 1978, Occurrence in yeast of L-galactonolactone oxidase which is similar to a key enzyme for ascorbic acid biosynthesis in animals, L-gulonolactone oxidase. Arch. Biochem. Biophys. 191 479-486. 

Ascorbic acid is involved in carnitine biosynthesis. Carnitine (y-amino-P-hydroxybutyric acid, trimethylbetaine) (30) is a component of heart muscle, skeletal tissue, Uver and other tissues. It is involved in the transport of fatty acids into mitochondria, where they are oxidized to provide energy for the ceU and animal. It is synthesized in animals from lysine and methionine by two hydroxylases, both containing ferrous iron and L-ascorbic acid. Ascorbic acid donates electrons to the enzymes involved in the metabohsm of L-tyrosine, cholesterol, and histamine (128). 

As a number of excellent articles have been published that review various aspects of the biological roles of L-ascorbic acid,8 the biosynthesis of L-ascorbic acid in plants and animals,7-11 and radicals derived from L-ascorbic acid,12 these topics will not be treated. Likewise, the methods by which L-ascorbic acid is assayed13 and the uses of L-ascorbic acid and related molecules in a wide variety of assays and oxidation-reduction systems will not be discussed. 

Ascorbic acid is a vitamin in primates. In most other animals, it can be synthesized by a branch of the glucoronic acid pathway (Chapter 18). It is apparently not changed into any coenzyme in the human being and participates as a vitamin in a reducing capacity in several biochemical reactions. These include the post-translational hydroxylation of proline in collagen biosynthesis (Chapter 8) and in tyrosine metabolism (Chapter 20). Ascorbic acid is oxidized to dehydroascorbic acid, a diketo derivative of ascorbate. Scurvy is a deficiency disease caused by a shortage of dietary ascorbic acid. In children, this results in defective bone formation in adults, extensive bleeding occurs in a number of locations. Scurvy is to be suspected if serum ascorbic acid levels fall below 1 jug/mL. 

M7. Mapson, L. W., The biosynthesis of L-ascorbic acid in plants and animals. Proc. Intern, Congr. Biochem. 4th Congr. Vienna 11, 1-16 (1960). 

Many remarkable species differences have been found among the coenzymes. Most plants and animals synthesize their own ascorbic acid which is (among other tasks) essential for the hydroxylation of proline and lysine in the biosynthesis of collagen. However, Man, other primates, and the guinea pig are notable exceptions, so that for them, and for them alone, it is a vitamin, and must be taken in with food. 

If histamine degradation is a physiological function of vitamin C, it is necessary to delineate the tissue level of ascorbic acid required for this effect. In the rat, which is capable of synthesizing ascorbic acid, serum ascorbic acid rose from 1.10 mg/100 ml to 1.63 mg/100 ml within 30 min of immobilization stress, nearly a 50% increase (Nakano and Suzuki, 1984). Liver ascorbate in these animals fell significantly after 15 min of stress, then rose dramatically to over 60% of the initial value within the next 15 min, indicating elevated hepatic biosynthesis of the vitamin. Adrenal ascorbic acid stores fell to 50% of the initial value following immobilization stress, and these levels remained depressed at 4 hr post-stress. Blood histamine levels rose 80%, from 38 to 68 ng/ml, peaking at about 30 min post-stress (Nakano and Suzuki, 1984). Hence, in the rat, stress induced a rapid rise in serum ascorbate which was fueled by ascorbic acid mobilized from tissue stores and by hepatic synthesis of ascorbate. 

Figure 1 Biosynthesis of L-ascorbic acid and L-xylulose in animals.

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