RRC ID 11895
著者 Adler LN, Gomez TA, Clarke SG, Linster CL.
タイトル A novel GDP-D-glucose phosphorylase involved in quality control of the nucleoside diphosphate sugar pool in Caenorhabditis elegans and mammals.
ジャーナル J Biol Chem
Abstract The plant VTC2 gene encodes GDP-L-galactose phosphorylase, a rate-limiting enzyme in plant vitamin C biosynthesis. Genes encoding apparent orthologs of VTC2 exist in both mammals, which produce vitamin C by a distinct metabolic pathway, and in the nematode worm Caenorhabditis elegans where vitamin C biosynthesis has not been demonstrated. We have now expressed cDNAs of the human and worm VTC2 homolog genes (C15orf58 and C10F3.4, respectively) and found that the purified proteins also display GDP-hexose phosphorylase activity. However, as opposed to the plant enzyme, the major reaction catalyzed by these enzymes is the phosphorolysis of GDP-D-glucose to GDP and D-glucose 1-phosphate. We detected activities with similar substrate specificity in worm and mouse tissue extracts. The highest expression of GDP-D-glucose phosphorylase was found in the nervous and male reproductive systems. A C. elegans C10F3.4 deletion strain was found to totally lack GDP-D-glucose phosphorylase activity; this activity was also found to be decreased in human HEK293T cells transfected with siRNAs against the human C15orf58 gene. These observations confirm the identification of the worm C10F3.4 and the human C15orf58 gene expression products as the GDP-D-glucose phosphorylases of these organisms. Significantly, we found an accumulation of GDP-D-glucose in the C10F3.4 mutant worms, suggesting that the GDP-D-glucose phosphorylase may function to remove GDP-D-glucose formed by GDP-D-mannose pyrophosphorylase, an enzyme that has previously been shown to lack specificity for its physiological D-mannose 1-phosphate substrate. We propose that such removal may prevent the misincorporation of glucosyl residues for mannosyl residues into the glycoconjugates of worms and mammals.
巻・号 286(24)
ページ 21511-23
公開日 2011-6-17
DOI 10.1074/jbc.M111.238774
PII S0021-9258(19)49032-7
PMID 21507950
PMC PMC3122210
MeSH Amino Acid Motifs Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / physiology Carbohydrate Metabolism Cloning, Molecular Gene Expression Regulation* Glucosyltransferases / genetics* Glucosyltransferases / physiology HEK293 Cells Humans Kinetics Mammals / metabolism* Mice Models, Biological Nucleoside Diphosphate Sugars / chemistry* Nucleotidyltransferases / chemistry* Recombinant Proteins
IF 4.238
引用数 23
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm2679