Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the rat weaning period (about day 19 after birth) the intestinal maturation is accompanied by a drastic increase in the fucose content of mucosal glycoconjugates, concomitant with an increase in fucosyltransferase activities. The regulation of this fucosylation process appears to be a rather complex phenomenon, which involves several systems controlling fucosyltransferase activity or substrate availability. An endogenous protein inhibitor of the fucosyltransferase activities displays an opposite developmental pattern to that of fucosyltransferase activities, since its activity is high before weaning and is decreased 5-fold after weaning. Similarly, the GDP-fucose pyrophosphatase activity markedly decreases at weaning. The transformation of GDP-mannose into GDP-fucose increases early, at day 18, preceding the increase in fucosyltransferase activities. Before weaning, and especially at days 14 and 18, high levels of GDP-4-dehydro-6-deoxymannose, the product of the GDP-mannose 4,6-dehydratase activity, are produced during the transformation of GDP-mannose into GDP-fucose, even in excess of reduced coenzyme. This fact indicates that the second step of the transformation (epimerase-reductase reaction) could be a limiting factor for GDP-fucose availability before weaning, but not after weaning. The inverse relationship between the mucosal fucose content (or the fucosyltransferase activity) and the endogenous protein inhibitor during normal postnatal development supports the hypothesis of a physiological role for this inhibitor.
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PMID:Participation of an endogenous inhibitor of fucosyltransferase activities in the developmental regulation of intestinal fucosylation processes. 195 74

We have cloned the cDNA encoding human GDP-mannose 4,6-dehydratase, the first enzyme in the pathway converting GDP-mannose to GDP-fucose. The message is expressed in all tissues and cell lines examined, and the cDNA complements Lec13, a Chinese Hamster Ovary cell line deficient in GDP-mannose 4,6-dehydratase activity. The human GDP-mannose 4,6-dehydratase polypeptide shares 61% identity with the enzyme from Escherichia coli, suggesting broad evolutionary conservation. Purified recombinant enzyme utilizes NADP+ as a cofactor and, like its E. coli counterpart, is inhibited by GDP-fucose, suggesting that this aspect of regulation is also conserved. We have isolated the product of the dehydratase reaction, GDP-4-keto-6-deoxymannose, and confirmed its structure by electrospray ionization-mass spectrometry and high field NMR. Using purified recombinant human GDP-mannose 4,6-dehydratase and FX protein (GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase), we show that the two proteins alone are sufficient to convert GDP-mannose to GDP-fucose in vitro. This unequivocally demonstrates that the epimerase and reductase activities are on a single polypeptide. Finally, we show that the two homologous enzymes from E. coli are sufficient to carry out the same enzymatic pathway in bacteria.
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PMID:Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro. 952 24

The deoxyhexose sugar fucose has an important fine-tuning role in regulating the functions of glycoconjugates in disease and development in mammals. The two genetic model organisms Caenorhabditis elegans and Drosophila melanogaster also express a range of fucosylated glycans, and the nematode particularly has a number of novel forms. For the synthesis of such glycans, the formation of GDP-fucose, which is generated from GDP-mannose in three steps catalysed by two enzymes, is required. By homology we have identified and cloned cDNAs encoding these two proteins, GDP-mannose dehydratase (GMD; EC 4.2.1.47) and GDP-keto-6-deoxymannose 3,5-epimerase/4-reductase (GER or FX protein; EC 1.1.1.271), from both Caenorhabditis and Drosophila. Whereas the nematode has two genes encoding forms of GMD (gmd-1 and gmd-2) and one GER-encoding gene (ger-1), the insect has, like mammalian species, only one homologue of each (gmd and gmer). This compares to the presence of two forms of both enzymes in Arabidopsis thaliana. All corresponding cDNAs from Caenorhabditis and Drosophila, as well as the previously uncharacterized Arabidopsis GER2, were separately expressed, and the encoded proteins found to have the predicted activity. The biochemical characterization of these enzymes is complementary to strategies aimed at manipulating the expression of fucosylated glycans in these organisms.
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PMID:Reconstitution in vitro of the GDP-fucose biosynthetic pathways of Caenorhabditis elegans and Drosophila melanogaster. 1665