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Subcellular Biochemistry pp 17–39Cite as

Biochemistry and Molecular Biology of Ascorbic Acid Biosynthesis

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Part of the book series: Subcellular Biochemistry ((SCBI,volume 25))

Abstract

Ascorbic acid is synthesized by a variety of organisms of the animal and plant kingdoms. Among mammals, however, humans, other primates, and guinea pigs cannot exceptionally produce this vitamin, and as a consequence, they are subject to a vitamin C—deficiency disease, scurvy, if the supply of vitamin C from their diet is not sufficient. The genetic defect causing the inability to synthesize ascorbic acid in these animals arose as a result of a mutation that had occurred during their evolution, and this trait is currently carried in all individuals of the scurvy-prone species. In this sense, scurvy is an unusual type of inborn error of metabolism (Nishikimi and Udenfriend, 1977; Stone, 1967). Besides the above-mentioned scurvy-prone animals, there is a mutant rat strain that suffers from scurvy when fed a vitamin C—deficient diet (Mizushima et al., 1984). In this chapter we will focus on the genetic basis of the incapability of humans, guinea pigs, and the scurvy-prone mutant rat to biosynthesize ascorbic acid. In fact, elucidation of the human genetic defect at the gene level has long been a subject of interest for ascorbic acid research. We will also deal with the recent studies related to biosynthesis of ascorbic acid, including the terminal enzymes of the biosynthetic pathways of ascorbic acid.

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Abbreviations

bp:

base pairs

FAD:

flavine adenine dinucleotide

GLO:

L-gulono-γ-lactone oxidase

ODS rat:

osteogenic disorder Shionogi rat

UDPGT:

uridine diphosphate glucuronosyl-transferase

References

  • August, P. R., Flickinger, M. C, and Sherman, D. H., 1994, Cloning and analysis of a locus (mer) involved in mytomycin C resistance in Streptomyces lavendulae, J. Bacteriol. 176:4448–4454.

    PubMed  CAS  Google Scholar 

  • Berget, S. M., 1984, Are U4 small nuclear ribonucleoproteins involved in polyadenylation?, Nature 309:179–182.

    Article  PubMed  CAS  Google Scholar 

  • Birney, E. C, Jenness, R., and Hume, I. D., 1979, Ascorbic acid biosynthesis in mammalian kidney, Experientia 35:1425–1426.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Brandsch, R., 1994, A new family of flavoenzymes?, in Flavins and Flavoproteins 1993 (K. Yagi, ed.), pp. 807–810, Walter de Gruyter, Berlin.

    Google Scholar 

  • Bucher, P., 1990, Weight matrix descriptions of four eukaryotic RNA polymerase II promoter elements derived from 502 unrelated promoter sequences, J. Mol. Biol. 212:563–578.

    Article  PubMed  CAS  Google Scholar 

  • Burns, J. J., 1957, Missing step in man, monkey and guinea pig required for the biosynthesis of L-ascorbic acid, Nature 180:553.

    Article  PubMed  CAS  Google Scholar 

  • Burns, J. J., 1960, Ascorbic acid, in Metabolic Pathways, vol. 1 (D. M. Greenberg, ed.), pp. 341–356, Academic Press, New York.

    Google Scholar 

  • Chatterjee, I. B., 1973a, Evolution and the biosynthesis of ascorbic acid, Science 182:1271–1272.

    Article  CAS  Google Scholar 

  • Chatterjee, I. B., 1973b, Vitamin C synthesis in animals: Evolutionary trend, Sci. Cult. 39:210–212.

    CAS  Google Scholar 

  • Chatterjee, I. B., Kar, N. C, Ghosh, N. C, and Guha, B. C, 1961, Biosynthesis of L-ascorbic acid: Missing steps in animals incapable of synthesizing the vitamin, Nature 192:163–164.

    Article  PubMed  CAS  Google Scholar 

  • Chaudhuri, C. R., and Chatterjee, I. B., 1969, L-Ascorbic acid synthesis in birds: Phylogenetic trend, Science 164:435–436.

    Article  PubMed  CAS  Google Scholar 

  • Dabrowski, K., 1994, Primitive Actinopterigian fishes can synthesize ascorbic acid, Experientia 50:745–748.

    Article  CAS  Google Scholar 

  • Dykhuizen, D. E., Harrison, K. M., and Richardson, B. J., 1980, Evolutionary implications of ascorbic acid production in the Australian lungfish, Experientia 36:945–946.

    Article  PubMed  CAS  Google Scholar 

  • Fujitsuka, N., Yokozawa, T., Oura, H., Akao, T., Kobashi, K., Ienaga, K., and Nakamura, K., 1993, L-Gulono-γ-lactone oxidase is the enzyme responsible for the production of methylguanidine in the rat liver, Nephron 63:445–451.

    Article  PubMed  CAS  Google Scholar 

  • Grange, T., Roux, J., Rigaud, G., and Pictet, R., 1991, Cell-type specific activity of two glucocorticoid responsive units of rat tyrosine aminotransferase gene is associated with multiple binding sites for C/EBP and a novel liver-specific nuclear factor, Nucleic Acids Res. 19:131–139.

    Article  PubMed  CAS  Google Scholar 

  • Harada, Y., Shimizu, M., Murakawa, S., and Takahashi, T., 1979, Identification of FAD of D-gluconolactone dehydrogenase: D-Erythrobic acid producing enzyme of Penicillium cyaneo-fulvum, Agric. Biol. Chem. 43:2635–3636.

    Article  CAS  Google Scholar 

  • Hayashida, H., and Miyata, T., 1983, Unusual evolutionary conservation and frequent DNA segment exchange in class I genes of the major histocompatibility complex, Proc. Natl. Acad. Sci. USA 80:2671–2675.

    Article  PubMed  CAS  Google Scholar 

  • Heick, H. M. C., Graff, G. L. A., and Humpers, J. E. C., 1972, The occurrence of ascorbic acid among the yeasts, Can. J. Microbiol. 18:597–600.

    Article  PubMed  CAS  Google Scholar 

  • Hollmann, S., and Touster, O., 1962, Alterations in tissue levels of uridine diphosphate glucose dehydrogenase, uridine diphosphate glucuronic acid pyrophosphatase and glucuronyl transferase induced by substances influencing the production of ascorbic acid, Biochim. Biophys. Acta 26:338–352.

    Article  Google Scholar 

  • Horio, F., and Yoshida, A., 1993, Regulatory mechanism of ascorbic acid biosynthesis stimulated by xenobiotics, Vitamins (Japan) 67:657–665.

    CAS  Google Scholar 

  • Horio, F., Kimura, M., and Yoshida, A., 1983, Effect of several xenobiotics on the activities of enzymes affecting ascorbic acid synthesis in rats, J. Nutr. Sci. Vitaminol. 29:233–247.

    PubMed  CAS  Google Scholar 

  • Horio, F., Shibata, T., Makino, S., Machino, S., Hayashi, Y., Hattori, T., and Yoshida, A., 1993a, UDP glucuronosyltransferase gene expression is involved in the stimulation of ascorbic acid biosynthesis by xenobiotics in rats, J. Nutr. 123:2075–2084.

    CAS  Google Scholar 

  • Horio, F., Shibata, T., Naito, Y., Nishikimi, M., Yagi, K., and Yoshida, A., 1993b, L-Gulono-γ-lactone oxidase is not induced in rats by xenobiotics stimulating L-ascorbic acid biosynthesis, J. Nutr. Sci. Vitaminol. 39:1–9.

    CAS  Google Scholar 

  • Hosokawa, S., Tagaya, O., Mikami, T., Nozaki, Y., Kawaguchi, A., Yamatsu, K., and Shamoto, M., 1992, A new rat mutant with chronic conjugated hyperbilirubinemia and renal glomerular lesions, Lab. Anim. Sci. 42:27–34.

    PubMed  CAS  Google Scholar 

  • Imai, T., Hirai, M., and Oba, K., 1995, Flavin is a prosthetic group of L-galactonolactone dehydrogenase from sweet potato, Plant Cell Physiol. (Suppl.), 36:140.

    Google Scholar 

  • Isherwood, F. A., Chen, Y. T., and Mapson, L. W., 1953, Synthesis of L-ascorbic acid in plants and animals, Nature 171:348–349.

    Article  PubMed  CAS  Google Scholar 

  • Iyanagi, T., Watanabe, T., and Uchiyama, Y., 1989, The 3-methylcholanthrene-inducible UDP-glucuronosyltransferase deficiency in the hyperbilirubinemic rat (Gunn rat) is caused by a —1 frameshift mutation, J. Biol. Chem. 264:21302–21307.

    PubMed  CAS  Google Scholar 

  • Kawai, T., Nishikimi, M., Ozawa, T., and Yagi, K., 1992, A missense mutation of L-gulono-γ-lactone oxidase causes the inability of scurvy-prone osteogenic disorder rats to synthesize L-ascorbic acid, J. Biol. Chem. 267:21973–21976.

    PubMed  CAS  Google Scholar 

  • Kenney, W. C, Edmondson, D. E., Singer, T. P., Nakagawa, H., Asano, A., and Sato, R., 1976, Identification of the covalently bound flavin of L-gulono-γ-lactone oxidase, Biochem. Biophys. Res. Commun. 71:1194–1200.

    Article  PubMed  CAS  Google Scholar 

  • Kenney, W. C, Edmondson, D. E., Singer, T. P., Nishikimi, M., Noguchi, E., and Yagi, K., 1979, Identification of the covalently-bound flavin of L-galactonolactone oxidase from yeast, FEBS Lett. 97:40–42.

    Article  PubMed  CAS  Google Scholar 

  • Kimura, M., 1983, The Neutral Theory of Molecular Evolution, Cambridge University Press, Cambridge.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Koshizaka, T., Nishikimi, M., Tanaka, M., Nakashima, K., Ozawa, T., and Yagi, K., 1987, In vitro synthesis of L-gulono-γ-lactone oxidase by rabbit reticulocyte lysate, Biochem. Int. 15:779–783.

    PubMed  CAS  Google Scholar 

  • Koshizaka, T., Nishikimi, M., Ozawa, T., and Yagi, K., 1988, Isolation and sequence analysis of a complementary DNA encoding rat liver L-gulono-γ-lactone oxidase, a key enzyme for L-ascorbic acid biosynthesis, J. Biol. Chem. 263:1619–1621.

    PubMed  CAS  Google Scholar 

  • Kozak, M., 1991, Structural features in eukaryotic mRNAs that modulate the initiation of translation, J. Biol. Chem. 266:19867–19870.

    PubMed  CAS  Google Scholar 

  • Li, W.-H., and Tanimura, M., 1987, The molecular clock runs more slowly in man than apes and monkeys, Nature 326:93–96.

    Article  PubMed  CAS  Google Scholar 

  • Loewus, F. A., Wagner, G., and Yang, J. C., 1975, Biosynthesis and metabolism of ascorbic acid in plants, Ann. N.Y. Acad. Sci. 258:7–23.

    Article  PubMed  CAS  Google Scholar 

  • Loewus, M. W., Bedgar, D. L., Saito, K., and Loewus, F. A., 1990, Conversion of L-sorbosone to L-ascorbic acid by an NADP-dependent dehydrogenase in bean and spinach leaf, Plant Physiol. 94:1492–1495.

    Article  PubMed  CAS  Google Scholar 

  • Mapson, L. W., and Breslow, E., 1958, Biological synthesis of L-ascorbic acid: L-Galactono-γ-lactone dehydrogenase, Biochem. J. 68:395–406.

    PubMed  CAS  Google Scholar 

  • McLauchlan, J., Gaffney, D., Whitton, J. L., and Clements, J. B., 1985, The consensus sequence YGTGTTYY located downstream from the AATAAA signal is required for efficient formation of mRNA 3′ termini, Nucleic Acids Res. 13:1347–1368.

    Article  PubMed  CAS  Google Scholar 

  • Miyata, T., and Yasunaga, T., 1980, Molecular evolution of mRNA: A method for estimating evolutionary rates of synonymous and amino acid substitutions from homologous nucleotide sequences and its application, J. Mol. Evol. 16:23–36.

    Article  PubMed  CAS  Google Scholar 

  • Mizushima, Y, Harauchi, T., Yoshizaki, T., and Makino, S., 1984, A rat mutant unable to synthesize vitamin C, Experientia 40:359–361.

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa, H., and Asano, A., 1970, Ascorbate-synthesizing system in rat liver microsomes I. Gulonolactone-reducible pigment as a prosthetic group of gulonolactone oxidase, J. Biochem. (Tokyo) 68:737–746.

    CAS  Google Scholar 

  • Nakagawa, H., Asano, A., and Sato, R., 1975, Ascorbate-synthesizing system in rat liver microsomes II. A peptide-bound flavin as the prosthetic group of L-gulono-γ-lactone oxidase, J. Biochem. (Tokyo) 77:221–232.

    CAS  Google Scholar 

  • Nakajima, Y., Shantha, T. R., and Bourne, G. H., 1969, Histochemical detection of L-gulonolactone: Phenazine methosulfate oxidoreductase activity in several mammals with special reference to synthesis of vitamin C in primates, Histochemie 18:293–301.

    PubMed  CAS  Google Scholar 

  • Nakamura, T., Satoh, T., Horie, T., Sagami, F., and Tagaya, O., 1989, Strain differences of rat liver carboxylesterase activities related to the phenotype difference of esterase-3 (egasyn), Res. Commun. Chem. Pathol. Pharmacol. 66:451–459.

    PubMed  CAS  Google Scholar 

  • Nei, M., and Gojobori, T., 1986, Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions, Mol. Biol. Evol. 3:418–426.

    PubMed  CAS  Google Scholar 

  • Nishikimi, M., and Udenfriend, S., 1976, Immunologic evidence that the gene for L-gulono-γ-lactone oxidase is not expressed in animals subject to scurvy, Proc. Natl. Acad. Sci. USA 73:2066–2068.

    Article  PubMed  CAS  Google Scholar 

  • Nishikimi, M., and Udenfriend, S., 1977, Scurvy as an inborn error of ascorbic acid biosynthesis, Trends Biochem. Sci. 2:111–113.

    Article  CAS  Google Scholar 

  • Nishikimi, M., Tolbert, B. M., and Udenfriend, S., 1976., Purification and characterization of L-gulono-γ-lactone oxidase from rat and goat liver, Arch. Biochem. Biophys. 175:427–435.

    Article  PubMed  CAS  Google Scholar 

  • Nishikimi, M., Noguchi, E., and Yagi, K., 1978, Occurrence in yeastof 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.

    Article  PubMed  CAS  Google Scholar 

  • Nishikimi, M., Koshizaka, T., Mochizuki, H., Iwata, H., Makino, S., Hayashi, Y., Ozawa, T., and Yagi, K., 1988a, L-Gulono-γ-lactone oxidase deficiency in rats with osteogenic disorder: Enzymological and immunochemical studies, Biochem. Int. 16:615–621.

    CAS  Google Scholar 

  • Nishikimi, M., Koshizaka, T., Ozawa, T., and Yagi, K., 1988b, Occurrence in humans and guinea pigs of the gene related to their missing enzyme L-gulono-γ-lactone oxidase, Arch. Biochem. Biophys. 267:842–846.

    Article  CAS  Google Scholar 

  • Nishikimi, M., Koshizaka, T., Kondo, K., Ozawa, T., and Yagi, K., 1989, Expression of the mutant gene for L-gulono-γ-lactone oxidase in scurvy–prone rats, Experientia 45:126–129.

    Article  PubMed  CAS  Google Scholar 

  • Nishikimi, M., Kawai, T., Ozawa, T., and Yagi, K., 1992, Guinea pigs possess a highly mutated gene for L-gulono-γ-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species, J. Biol. Chem. 267:21967–21972.

    PubMed  CAS  Google Scholar 

  • Nishikimi, M., Fukuyama, R., Minoshima, S., Shimizu, N., and Yagi, K., 1994a, Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-γ-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man, J. Biol. Chem. 269:13685–13688.

    CAS  Google Scholar 

  • Nishikimi, M., Kobayashi, J., and Yagi, K., 1994b, Production by a baculovirus expression system of the apoprotein of L-gulono-γ-lactone oxidase, a flavoenzyme possessing a covalently bound FAD, Biochem. Mol. Biol. Int. 33:313–320.

    CAS  Google Scholar 

  • Oba, K., Fukui, M., Imai, Y., Iriyama, S., and Nogami, K., 1994, L-Galactono-γ-lactonedehydrogenase: Partial characterization, induction of activity and role in the synthesis of ascorbic acid in wounded white potato tuber tissue, Plant Cell Physiol. 35:473–478.

    CAS  Google Scholar 

  • Oba, K., Ishikawa, S., Nishikawa, M., Mizuno, H., and Yamamoto, T., 1995, Purification and properties of L-galactono-γ-lactone dehydrogenase, a key enzyme for ascorbic acid biosynthesis, from sweet potato roots, J. Biochem. (Tokyo) 117:120–124.

    CAS  Google Scholar 

  • Ramji, D. P., Tadros, M. H., Hardon, E. M., and Cortese, R., 1991, The transcription factor LF-A1 interacts with a bipartite recognition sequence in the promoter regions of several liver-specific genes, Nucleic Acids Res. 19:1139–1146.

    Article  PubMed  CAS  Google Scholar 

  • Saito, K., Nick, J. A., and Loewus, F. A., 1990, D-Glucosone and L-sorbosone, putative intermediates of L-ascorbic acid biosynthesis in detached bean and spinach leaves, Plant Physiol. 94:1496–1500.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Sato, P., and Udenfriend, S., 1978, Scurvy-prone animals, including man, monkey, and guinea pig do not express the gene for gulonolactone oxidase, Arch. Biochem. Biophys. 187:158–162.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Shigeoka, S., Nakano, Y., and Kitaoka, S., 1979, The biosynthetic pathway of L-ascorbic acid in Euglena gracilis Z, J. Nutr. Sci. Vitaminol. 25:299–307.

    PubMed  CAS  Google Scholar 

  • Shimazono, N., and Mano, Y., 1961, Enzymatic studies on the metabolism of uronic and aldonic acids related to L-ascorbic acid in animal tissues, Ann. N.Y. Acad. Sci. 92:91–104.

    Article  CAS  Google Scholar 

  • Stone, I., 1967, The genetic disease, hypoascorbemia. A fresh approach to an ancient disease and some of its medical implications, Acta Genet. Med. Gemellol. 16:52–62.

    PubMed  CAS  Google Scholar 

  • Swimmer, C, and Shenk, T, 1985, Selection of sequence elements that substitute for the standard AATAAA motif which signals 3′ processing and polyadenylation of late simian virus 40 mRNAs, Nucleic Acids Res. 13:8053–8063.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, T., Yamashita, H., Kato, E., Mitsumoto, M., and Murakawa, S., 1976, Purification and some properties of D-glucono-γ-lactone dehydrogenase. D-Erythrobic acid producing enzyme of Penicillium cyaneo–fulvum, Agric. Biol. Chem. 40:121–129.

    Article  CAS  Google Scholar 

  • Thomas, P., Bally, M. B., and Neff, J. M., 1985, Influence of some environmental variables on the ascorbic acid status of mullet, Mugil cephalus L., tissues II. Seasonal fluctuations and biosynthetic ability, J. Fish Biol. 27:47–57.

    Article  CAS  Google Scholar 

  • Touhata, K., Toyohara, H., Kinoshita, M., Mitani, T, Sato, M., and Sakaguchi, M., 1993, Molecular evolution of gulonolactone oxidase in vertebrates II. Purification of the enzyme from lamprey kidney, in Abstracts for the Meetings of Japanese Society of Scientific Fisheries (October), p. 196.

    Google Scholar 

  • Toyohara, H., Touhata, K., Kinoshita, M., Mitani, T., Sato, M., Sakaguchi, M., Nishikimi, M., and Yagi, 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.

    Google Scholar 

  • Wilson, R. P., 1973, Absence of ascorbic acid synthesis in channel catfish, Ictaluruspunctatus and blue catfish, Ictalurus jmeatus, Comp. Biochem. Physiol. 46B:635–638.

    Article  Google Scholar 

  • Winkelman, J., and Lehninger, A. L., 1958, Aldono– and uronolactonase of animal tissues, J. Biol. Chem. 233:794–799.

    PubMed  CAS  Google Scholar 

  • Yagi, K., Koshizaka, T., Kito, M., Ozawa, T., and Nishikimi, M., 1991, Expression in monkey cells of the missing enzyme in L-ascorbic acid biosynthesis, L-gulono-γ-lactone oxidase, Biochem. Biophys. Res. Commun. 177:659–663.

    Article  PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Applied Biochemistry, Yagi Memorial Park, Gifu, Mitake, 505-01, Japan

    Morimitsu Nishikimi & Kunio Yagi

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  1. Morimitsu Nishikimi
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  2. Kunio Yagi
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  1. Institute of Zoology, University of Mainz, Mainz, Germany

    J. Robin Harris

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© 1996 Plenum Press, New York

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Nishikimi, M., Yagi, K. (1996). Biochemistry and Molecular Biology of Ascorbic Acid Biosynthesis. In: Harris, J.R. (eds) Subcellular Biochemistry. Subcellular Biochemistry, vol 25. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0325-1_2

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  • DOI: https://doi.org/10.1007/978-1-4613-0325-1_2

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