Molecular basis for the deficiency in humans of gulonolactone oxidase, a key enzyme for ascorbic acid biosynthesis.

@article{Nishikimi1991MolecularBF,
  title={Molecular basis for the deficiency in humans of gulonolactone oxidase, a key enzyme for ascorbic acid biosynthesis.},
  author={Morimitsu Nishikimi and Kunio Yagi},
  journal={The American journal of clinical nutrition},
  year={1991},
  volume={54 6 Suppl},
  pages={
          1203S-1208S
        }
}
  • M. Nishikimi, K. Yagi
  • Published 1 December 1991
  • Biology, Medicine
  • The American journal of clinical nutrition
The inability of humans to synthesize L-ascorbic acid is known to be due to a lack of L-gulono-gamma-lactone oxidase, an enzyme that is required for the biosynthesis of this vitamin. [...] Key Result Sequence analysis study indicated that the human L-gulono-gamma-lactone oxidase gene has accumulated a large number of mutations since it stopped being active and that it now exists as a pseudogene in the human genome.Expand
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This review focuses on aldonolactone oxidoreductases, a subgroup of the vanillyl alcohol oxidase (VAO; EC 1.3.38) superfamily, enzymes that catalyze the terminal step in AsA biosynthesis in bacteria, protozoa, animals, and plants.
Metabolic engineering of an alternative pathway for ascorbic acid biosynthesis in plants
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Transgenic tobacco and lettuce plants expressing a rat cDNA encoding L-gulono-γ-lactone oxidase accumulated up to seven times more ascorbic acid than untransformed plants demonstrate that basal levels of ascorBic acid in plants can be significantly increased by expressing a single gene from the animal pathway.
L‐gulono‐7‐lactone oxidase expression and vitamin C synthesis in the brain and kidney of the African lungfish, Protopterus annectens
  • B. Ching, Jasmine L. Y. Ong, +4 authors Y. Ip
  • Chemistry, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2014
TLDR
Test the hypothesis that the brain of Protopterus annectens expressed L‐gulono‐γ‐lactone oxidase (gulo/Gulo), the enzyme catalyzing the last step of ascorbate biosynthesis, and could maintain high concentrations of asCorbate during estivation to find out whether this ability might contribute to the ability of P.annectens to undergo prolonged estivation on land.
Is ascorbic acid a key signaling molecule integrating the activities of 2-oxoglutarate-dependent dioxygenases? Shifting the paradigm
Abstract The integration of different environmental cues and the harmonization of proper responses require molecular communication at different levels. Enzymes belonging to the large superfamily of…
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The increasing knowledge of the functions of ascorbate and of its molecular sites of action can mechanistically substantiate a place for asCorbate in the treatment of various diseases.
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An up‐to‐date review on ascorbate synthesis in fishes and the possible future directions of study in view of the discovery of the unusual site of asCorbate biosynthesis is provided.
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It is suggested that an endogenous retrovirus or other retroviral-like element may have been involved in mutating the gene coding for gulonolactone oxidase, the terminal step in ascorbate synthesis, approximately 45 million years ago, and may have played a pivotal role in primate and H. sapiens evolution.
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The results indicated that, although AA synthesis might occur in the ovaries, the amount of AA which is synthesized in ovaries must be quite low and insufficient to influence the AA content in ovary.
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The Gulo knockout mouse provides a useful model for the metabolomic examination of vitamin C deficiency and the results of the study highlight the metabolites and pathways known to require ascorbate for proper flux.
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References

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TLDR
The L-gulono-gamma-lactone oxidase-related sequences in the guinea pig and human genomes may represent the remnants of the gene of the enzyme that were once active but became nonfunctional during the course of evolution.
Isolation and sequence analysis of a complementary DNA encoding rat liver L-gulono-gamma-lactone oxidase, a key enzyme for L-ascorbic acid biosynthesis.
TLDR
Hydropathy analysis of the deduced amino acid sequence revealed several hydrophobic regions, suggesting that they anchor the protein into the microsomal membranes of scurvy-prone animals.
Immunologic evidence that the gene for L-gulono-gamma-lactone oxidase is not expressed in animals subject to scurvy.
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Missing Step in Man, Monkey and Guinea Pig required for the Biosynthesis of L-Ascorbic Acid
TLDR
Man and monkey also cannot convert L-gulonolactone to L-ascorbic acid, a step which is catalysed in rats by enzymes present in liver.
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TLDR
The transient appearance of an intermediate, which is considered to be 2-oxo-L-gulono-γ-lactone, was demonstrated by spectrophotometric tracing of the formation of L-ascorbic acid.
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TLDR
Tests on the enzymes required for the synthesis of ascorbic acid within animals could prove of value in deducing which ancestor of Man lost this important biochemical system and at what point in Time it was lost.
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TLDR
The ability of several species of birds to synthesize L-ascorbic acid is correlated with their phylogeny, and the pattern of evolution of the ascorbic acid pathway among birds is similar to that among mammals.
Scurvy-prone animals, including man, monkey, and guinea pig, do not express the gene for gulonolactone oxidase.
TLDR
Man, monkeys, and guinea pigs cannot synthesize ascorbic acid due to a lack of gulonolactone oxidase activity, and it is found that all three of these species do not contain immunologically cross-reacting material to gulonolate oxidase.
Evolution and the Biosynthesis of Ascorbic Acid
TLDR
The ability to synthesize ascorbic acid is absent in the insects, invertebrates, and fishes and a similar transition in the biosynthetic ability was observed in the branched evolution of the birds.
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