Ascorbic acid metabolism, pathways

Another part of the urinary oxalate is of endogenous origin. It is a product of ascorbic acid metabolism in rats (C19) and in man (H14, L3). The metabolic pathway leading from ascorbic to oxalic acid is unknown. 

Glucuronate is reduced to L-gulonate in an NADPH-dependent reaction L-gulonate is the direct precursor of ascorbate in those animals capable of synthesizing this vitamin. In humans and other primates as well as guinea pigs, ascorbic acid cannot be synthesized because of the absence of L-g ulonolactone oxidase. L-Gulonate is metabolized ultimately to D-xylulose 5-phosphate, a constituent of the pentose phosphate pathway. 

Figure 20-2 Some pathways of metabolism of D-glucuronic acid and of ascorbic acid, vitamin C.

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. 

Jain, A.K., and Nessler, C.L., 2000. Metabolic engineering of an alternative pathway for ascorbic acid biosynthesis in plants. Mol. Breeding 6 73-78. 

Side-chain oxidized derivatives of ascorbic acid are also implicated in the catabolism of ascorbic acid in plants. Loewus et al. (62) have established the intermediacy of ascorbic acid in the biosynthesis of tartaric acid in the grape. Labeling studies have established a metabolic pathway that must involve C5 and C6 oxidation of ascorbic acid. 

The metabolism of ascorbic acid has yet to be clarified. Only one of the major water-soluble urinary metabolites of ascorbic acid has been isolated and characterized the others and the matabolic pathways involved are yet to be defined. When these pathways and their intermediates are understood, there will be good possibilities for significant nutritional and medical innovation. 

The function of ascorbic acid in tyrosine metabolism is complicated by the fact that not only does it participate in more than one stage of the normal pathway, but it can also participate in certain nonspecific reactions. It is not known to what extent the mechanisms of these various functions are related. Nonspecific hydroxylation of aromatic compounds (22, 23,... 

Besides ascorbic acid, glycine is the most important source of oxalic acid (W5). The metabolic pathway leading from glycine to oxalic acid via glyoxylic acid (which can be readily converted to glycolic acid) and the enzyme systems involved in that pathway have been recently... 

Glucuronate, once formed, can reenter the pathways of glucose metabolism through reactions that eventually convert it to D-xylulose 5-phosphate, an intermediate of the pentose phosphate pathway. In most mammals other than humans, an intermediate of this pathway is the precursor of ascorbic acid (vitamin C). Humans, however, are deficient in this pathway and cannot synthesize vitamin C. 

Ascorbic Acid A six carbon compound related to glucose. It is found naturally in dtrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a redudng agent and coenzyme in several metabolic pathways. Vitamin C is... 

Ascorbic acid, which can reverse methemoglobin by an alternate metabolic pathway, is of minimal use acutely because of its slow action. 

Metabolic pathway engineering and ascorbic acid manufacture... 

Of greater immediate relevance for this industrial biocatalysis is the use of genetic engineering to incorporate new proteins into a cell. The commercial products of this technology, such as insulin and chymosin, do not affect the metabolism of the producing cell they are end-products of their own right. If, on the other hand, the cell is altered to produce a new enzyme which is metabolically active in the cell itself, it becomes possible to extend a metabolic pathway by one or two desirable steps, an action which cannot be achieved through the normal process of mutation and selection, which can only act on the complement of enzymes which the cell already contains. This concept has been applied to a number of commercial processes, one of which is the manufacture of ascorbic acid. 

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