L-gulonolactone oxidase

Vitamin C is L-ascorbic acid (chemically 2-oxogulonolactone). The two hydroxyl groups have acidic properties. By releasing a proton, ascorbic acid therefore turns into its anion, ascorbate. Humans, apes, and guinea pigs require vitamin C because they lack the enzyme L-gulonolactone oxidase (tl.3.8), which catalyzes the final step in the conversion of glucose into ascorbate. 

Ascorbic acid is derived from glucose via the uronic acid pathway. The enzyme L-gulonolactone oxidase responsible for the conversion of gulonolactone to ascorbic acid is absent in primates, thus making ascorbic acid an essential in the diet. 

Diketogulonate cannot be reduced back to ascorbate. Most animals synthesize ascorbate using the path shown in Fig. 7.7, but primates including humans have accumulated mutations in the gene for L-gulonolactone oxidase and cannot synthesize ascorbate de novo. They require a dietary source of vitamin C to compensate for the gradual loss of dehy-droascorbate. The current Recommended Dietary Allowance (RDA) from the US Food and Drug Administration is 60-95 mg/day. 

The ready oxidation of ascorbic acid will catalyze chemical changes in a number of other substances. Thus, unsaturated fatty acids in lecithins and tissues are catalytically oxidized in the presence of ascorbic acid to a substance producing color with thiobarbiturate (B21). The product of the ascorbic acid-catalyzed oxidation is malonaldehyde, which can also inhibit L-gulonolactone oxidase, the enzyme forming ascorbic acid (Cl). It has been suggested that this enzyme inhibition may occur in vivo in animals deficient in vitamin E, a compound believed to have antioxidant actions which would prevent the ascorbic acid-catalyzed lipid oxidation from giving rise to malonaldehyde. It is quite probable that the active intermediate in the formation of malonaldehyde is the monodehydroascorbate radical which initiates the lipid oxidation. 

Roy and Guha (R24) induced experimental scurvy in a bird, the red-vented bulbul Pycrorotus cafer). The birds lost weight and feathers and died after 16 to 45 days on a scorbutigenic ration. The scorbutic birds recovered with administration of ascorbic acid. The susceptibility to scurvy correlated well with the lack of activity in this species of the specific liver enzyme which is indispensable for ascorbic acid biosynthesis (L-gulonolactone oxidase). This enzyme was present in the liver of bank-myna Acridotheres ginginmanus) which was not susceptible to scurvy. 

L-Gulonolactone Oxidases.—A rapid and quantitative assay for L-gulonolactone oxidase in mammalian livers has been described maximal recovery of the enzyme was achieved by homogenization of the livers in a solution of sodium deoxy-cholate, The effects of sampling and of storing on the enzymic activity were assessed. 

Bleeg, H. S., and Christensen, F., 1982, Biosynthesis of ascorbate in yeast. Purification of L-galactono-1,4-lactone oxidase with properties different from mammalian L-gulonolactone oxidase, Eur. J. Biochem. 127 391-396. 

Kiuchi, K., Nishikimi, M., and Yagi, K., 1982, Purification and characterization of L-gulonolactone oxidase from chicken kidney microsomes. Biochemistry 21 5076-5082. 

Sato, P., and Grahn, I., 1981, Administration of chicken L-gulonolactone oxidase to guinea pigs evokes ascorbic acid synthetic capacity. Arch. Biochem. Biophys. 210 609-616. 

Sato, P., Nishikimi, M., and Udenfriend, S., 1976, Is L-gulonolactone oxidase the only enzyme missing in animals subject to scurvy , Biochem. Biophys. Res. Commun. 71 293-299. 

K., 1992, Molecular evolution of L-gulonolactone oxidase in vertebrates I. Its distribution among vertebrates, in Abstracts for the Meetings of Japanese Society of Scientific Fisheries (October), p. 150. 

Yamamoto, Y, Sato, M., and Ikeda, S., 1978, Existence of L-gulonolactone oxidase in some teleosts. Bull. Jpn. Soc. Sci. Fish. 44 775-779. 

FIGURE 4. Ascorbate metabolism. Main pathways of ascorbate synthesis, antioxidant action, reductive recycling, and catabolism. DHA = dehydroascorbate, R = free radical, 1 = L-gulonolactone oxidase, 2 = DHA reductase, 3 = AFR reductase. Steps 2 and 3 could also occur by nonenzymatic reaction. 

Nishikimi, M., Koshizaka, T., Ozawa, T., and Yagui, K., 1988, Occurrence in humans and guinea pigs of the gene related to their missing enzyme L-gulonolactone oxidase. Arch. Biochem. Biophys. 267 842-846. 

Vitamin C—also called ascorbic acid, dehydroascorbic acid, hexuronic acid, and the antiscorbutic vitamin—is the very important substance, first found in citrus fruits, which prevents scurvy, one of the oldest scourges of mankind. All animal species appear to require vitamin C, but a dietary need is limited to humans, guinea pigs, monkeys, bats, certain fish, and perhaps certain reptiles. These species lack the enzyme L-gulonolactone oxidase which is necessary for vitamin C synthesis from 6-carbon sugars. 

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