Catabolism ascorbic acid

Banhegyi, G., and Loewus, F.A., 2004, Ascorbic acid catabolism Breakdown pathways in animals and plants. In Asard, H., May, J.M., and Smirnoff, N. (eds.), Vitamin C. Functions and Biochemistry in Animals and Plants. BIOS Sci. Publ., London and New York, pp. 31-48. 

Biochemical Functions. Ascorbic acid has various biochemical fimctions, involving, for example, coUagen synthesis, immune fimction, drug metabohsm, folate metabolism, cholesterol catabolism, iron metabolism, and carnitine biosynthesis. Clear-cut evidence for its biochemical role is available only with respect to coUagen biosynthesis (hydroxylation of prolin and lysine). In addition, ascorbic acid can act as a reducing agent and as an effective antioxidant. Ascorbic acid also interferes with nitrosamine formation by reacting directly with nitrites, and consequently may potentially reduce cancer risk. 

Most of the oxalate in the body arises from endogenous sources, rather than the diet. About 40% of the oxalate formed in the body arises from ascorbic acid. About arises from 2-carbon precursors, such as glycine and elhanolamine. Only about 0.1% of the body s glycine is catabolized via oxalate formation. Some people increase their intake of ascorbic acid to levels above the RDA by taking supplements. Consumption of large amounts of ascorbate results in increases in urinary oxalate in some persons but not in others. The normal, basal level of urinary oxalate is about 50 mg/day. The daily intake of 3,0 g of ascorbic acid may double the normal levels of urinary oxalate and thus increase the risk for calcium oxalate stones. 

The pathways for the formation of oxalate from glycine, ethanolamine, and ascorbic acid, are shown in Figure 10.41. Apparently, oxalate has no function in the body, nor is It catabolized to carbon dioxide. Oxalate occurs in plants as sodium... 

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. 

A DHA lactonase has been described (76,77) in the ox, rabbit, rat, and guinea pig. In the ox the lactonase is present in several tissues but is most abundant in the liver. The enzyme appears to be absent in human and monkey tissue. This result is consistent with the observation that primates and fishes do not catabolize labeled ascorbic acid to carbon dioxide. AA and DHA appear to be metabolized into a series of water soluble products that are excreted in the urine, but 2,3-DKG is decar-boxylated and otherwise degraded to intermediates that enter the C5 and C4 carbohydrate pools (78). 

An important discovery in 1969 (1) linked the catabolism of L-ascor-bic acid to tartaric acid biosynthesis. When immature grape berries were fed L-[l- C]ascorbic acid over a 24-h period, 72% of the acid extractable... 

Table II. L-Ascorbic Acid Catabolism in Grape Leaves (Metabolic Period, 24 h)...

Our results have led us to suggest a role for L-ascorbic acid in phloem transport (9) in which ascorbic acid is translocated from its biosynthetic site in the leaf to a catabolic site in the fruit cluster where C4-C5 cleavage of the carbon chain produces tartaric acid and a putative C2 precursor of carbohydrate biosynthesis. The sugar/organic acid balance that influences grape quality in winemaking may well be determined by the role of ascorbic acid as the precursor of tartaric acid. 

Figure 3. Time course of i.-[U- C]ascorbic acid catabolism in the lemon...

In guinea pigs there is considerable conversion of ascorbic acid to respiratory carbon dioxide (3,37). Further, the entire carbon chain of ascorbic acid is subjected to extensive oxidation to carbon dioxide (3,21), Following injection of (1- C)ascorbic acid, 66% of the label was recovered as ( C)carbon dioxide during 10 d up to 30-40% of the dose was catabolized to carbon dioxide during the first 24 h (20). Our data indicate that in a time period of 216 h about 65% of the oral dose of (1- C)ascorbic acid is exhaled as labeled carbon dioxide (Table I). The maximum rate of excretion occurred at 0.5 h (Figure 6), and we derived from this radioactivity-time curve that within the first 12 h about 30% of the label was exhaled (36% after 24 h). 

The functions and fate of i.-ascorbic acid in humans and other primates are reviewed in this chapter. Topics included are use of subhuman primates for research in nutrition evolution and subsequent loss of ascorbic acid biosynthesis absorption, tissue transport, and distribution of ascorbic acid and catabolism, functions, and requirements of ascorbic acid. In retrospect, the insight provided by this chapter suggests new work areas of emphasis for developing better understanding of the vitamins role in human health. 

In the diet and at the tissue level, ascorbic acid can interact with mineral nutrients. In the intestine, ascorbic acid enhances the absorption of dietary iron and selenium reduces the absorption of copper, nickel, and manganese but apparently has little effect on zinc or cobalt. Ascorbic acid fails to affect the intestinal absorption of two toxic minerals studied, cadmium and mercury. At the tissue level, iron overload enhances the oxidative catabolism of ascorbic acid. Thus, the level of dietary vitamin C can have important nutritional consequences through a wide range of inhibitory and enhancing interactions with mineral nutrients. 

Effects of Excess Tissue Iron on Ascorbic Acid Metabolism. Epidemiological observations among the Bantu of South Africa showed an apparent association of clinical scurvy in adult males with hemosiderosis common to this group. Both plasma clearance of ascorbic acid and urinary excretion of ascorbic acid were altered in severe iron overload plasma clearance was increased and urinary excretion was decreased in siderotic subjects (40,41), The evidence was interpreted as a demonstration of enhanced oxidative catabolism of ascorbic acid in the presence of excess tissue iron. 

There is reason to conclude that vitamin deficiency might contribute to arteriosclerosis. There is a correlation between elevated homocysteine levels and incidence of cardiovascular disease (59). There is debate as to whether homocysteine contributesto the dam e of cells on the interior of blood vessel or whether homocysteine is a marker of intensive cell repair and formation of replacement cells. Nevertheless, administration of pyridoxine, folic acid, and (yanocobalamin are being recommended along with the two antioxidant vitamins, a-tocopherol and ascorbic acid for arteriosclerosis. Vitamin Bg is required for two of the steps in the catabolism of homocysteine to succinyl CoA (Fig. 8.52). Note in Fig. 8.52 (bottom) that biotin and a coenzyme form of cobalamin also are required for... 

Product stability and performance can be affected by exposure to several oxidative sources, including oxygen, free radicals, UV radiation, oxidative enzymes, catabolic oxidation, and chemical oxidation. Many antioxidants are also good UV absorbers due to their conjugated chemical structure. Typical antioxidants found in cosmetic products are flavonoids, polyphenols, carotenoids, thiols, tocopherol (vitamin E) and ascorbic acid (vitamin C) [71,72], According to Black [73], a combination of antioxidants from different classes is more effective than a single antioxidant due to an antioxidant cascade mechanism. 

The balance between the anabolism and catabolism of HA is maintained by the inhibitors of hyaluronidases. Heparin is a known and well-characterized inhibitor of hyaluronidase [132]. Chitosan inhibits HA degradation by venom and bovine testicular hyaluronidases [133]. Cis-unsaturated fatty acids can also inhibit the hyaluronidase activity [134]. Certain anti-inflammatory drugs including saly-cylates, indomethacin and dexamethasone are also known to exert anti-hyaluronidase activity [133, 135]. Ascorbic acid [136], as well as plant derived bioactive compounds, such as flavonoids, tannins, pectins, curcumins, cou-marins, gylcyrrhizin are used to block hyaluronidase activity [100]. 

Salomon, L. L., Ascorbic acid catabolism in guinea pigs. J. Biol. Chem. 228, 163-170 (1957). 

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