Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036474 (scurvy)
 685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-Gulono-gamma-lactone oxidase (L-gulono-gamma-lactone:oxygen 2-oxidoreductase, EC 1.1.3.8) is the enzyme that catalyzes the terminal step of L-ascorbic acid biosynthesis in mammalian liver. The absence of the oxidase activity in primates and guinea pigs is the reason why these animals are subject to scurvy, which must be considered an inborn error of metabolism. Attempts were made to determine if a protein immunologically crossreactive with L-gulono-gamma-lactone oxidase is present in these animals. Detergent-solubilized microsomal preparations from guinea pig and African green monkey liver did not precipitate the antisera directed to either rat or goat enzyme, nor did any of the other cell fractions obtained from guinea pig liver react with either antiserum. No crossreactive protein was detectable in guinea pig microsomes even with the sensitive procedure or micro-complement fixation. On the other hand, extracts of all 10 other mammalian (4 orders) liver microsomes tested were shown to contain L-gulono-gamma-lactone oxidase activity that did crossreact with antibodies to the rat and goat enzymes. One explanation of these findings is that, in the guinea pig, and perhaps in primates too, the structural gene for L-gulono-gamma-lactone oxidase is not expressed.
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PMID:Immunologic evidence that the gene for L-gulono-gamma-lactone oxidase is not expressed in animals subject to scurvy. 81 30

L-Gulono-gamma-lactone oxidase (GLO), an enzyme that is missing in scurvy-prone animals, was produced in COS-1 cells by transfection with a minigene constructed from pSVL vector and rat GLO cDNA. A functional GLO protein was expressed, which was indistinguishable from rat GLO in molecular size. The microsomes obtained from the transfected COS-1 cells showed GLO activity comparable to that in rat liver microsomes.
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PMID:Expression in monkey cells of the missing enzyme in L-ascorbic acid biosynthesis, L-gulono-gamma-lactone oxidase. 204 88

Potential therapeutic usefulness of administered enzymes is limited by toxicity and allergenicity. To overcome these problems we are using scurvy to test various enzyme modifications that may be suitable for therapy. L-Gulonolactone oxidase, which catalyzes the final step in ascorbic acid biosynthesis, is immunoprecipitated with specific antisera from rabbits and then cross-linked with glutaraldehyde. The modified enzyme retains activity sufficient to elicit ascorbic acid synthesis in scorbutic guinea pigs. Intraperitoneal injection of this altered enzyme to animals supplemented with L-gulonolactone increases plasma concentrations of the vitamin. Importantly, multiple doses of the complex are tolerated. Therefore, it is possible to prolong survival time of animals fed an ascorbic acid-deficient diet by this enzyme replacement therapy. This procedure can also be applied to other enzymes that have potential therapeutic use. Serum cholinesterase and asparaginase both retain activity after this modification and are tolerated in single or in weekly repeated injections. Following three or four weekly injections, an anaphylactic reaction to serum but not to enzyme can be elicited if they are injected intravascularly. We conclude that the stability of the immobilized foreign enzyme is a critical factor in lessening the toxicity to multiple injections of these foreign proteins.
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PMID:Heterologous immunoprecipitates also have potential for therapeutic use. 310 56

L-Gulono-gamma-lactone oxidase, one of the microsomal flavin enzymes, catalyzes the last step of L-ascorbic acid biosynthesis in many animals; however, it is missing in scurvy-prone animals such as humans, primates, and guinea pigs. A cDNA clone for this enzyme was isolated by screening a rat liver cDNA expression library in lambda gt11 using antibody directed against the enzyme. The cDNA clone contained 2120 nucleotides and an open reading frame of 1320 nucleotides encoding 440 amino acids of the protein with a molecular weight of 50,605. The amino-terminal sequence (residues 1-33) of the enzyme isolated from rat liver completely coincided with the corresponding part of the deduced amino acid sequence. The identity of the cDNA clone was further confirmed by the agreement of the composition of the deduced amino acids with that determined by amino acid analysis of the enzyme. Hydropathy analysis of the deduced amino acid sequence revealed several hydrophobic regions, suggesting that they anchor the protein into the microsomal membrane. The deduced amino acid sequence showed no obvious homology with the flavin-binding regions of other eight flavoenzymes.
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PMID:Isolation and sequence analysis of a complementary DNA encoding rat liver L-gulono-gamma-lactone oxidase, a key enzyme for L-ascorbic acid biosynthesis. 333 84