MetaCyc Pathway: GDP-glucose biosynthesis
Inferred from experiment

Enzyme View:

Pathway diagram: GDP-glucose biosynthesis

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisCarbohydrates BiosynthesisSugars BiosynthesisSugar Nucleotides BiosynthesisGDP-sugar Biosynthesis

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Homo sapiens, Sus scrofa

Expected Taxonomic Range: Archaea, Bacteria , Eukaryota

About 50 different nucleoside diphosphate sugars have been isolated, and many of these have been shown to be intermediates in the biosynthesis of various types of complex carbohydrates [Ning00]. These substances and the enzymes involved in their synthesis, i.e., the nueleoside diphosphate sugar pyrophosphorylases, have been found in many organisms, including microorganisms, plants and animals [Danishefsky67, Nikaido68, Hassid69].

The biological synthesis of GDP-α-D-glucose was first described in 1961 in bovine mammary gland [Carlson62]. The authors found that it was synthesized from GTP and α-D-glucopyranose 1-phosphate by the enzyme glucose-1-phosphate guanylyltransferase, which they partially purified. A similar enzyme was partially purified from human mast cell tumors [Danishefsky67]. That enzyme also had GDP-D-mannose pyrophosphorylase activity. Surprisingly, no further work has focused on this enzyme since the 1967 publication.

A dimeric GDP-D-mannose pyrophosphorylase (EC has been purified from pig liver, and was shown to have higher activity with GDP-α-D-glucose (assayed in the reverse direction) than with GDP-α-D-mannose [Szumilo93]. The purified small subunit from that enzyme was able to catalyze the GDP-D-mannose pyrophosphorylase activity on its own, but had no activity with α-D-glucopyranose 1-phosphate, prompting the authors to suggest that the (uncharacterized) large subunit may be responsible for the GDP-D-glucose pyrophosphorylase activity. This hypothesis has not been tested yet [Ning00].

Created 18-Sep-2007 by Caspi R, SRI International


Carlson62: Carlson, D.M., Hansen, R.G. (1962). "The isolation and synthesis of guanosine diphosphate glucose." J Biol Chem 237;1260-5. PMID: 13876631

Danishefsky67: Danishefsky I, Heritier-Watkins O (1967). "Nucleoside diphosphate glucose pyrophosphorylases in mast cell tumors." Biochim Biophys Acta 139(2);349-57. PMID: 6034677

Hassid69: Hassid WZ (1969). "Biosynthesis of oligosaccharides and polysaccharides in plants." Science 165(889);137-44. PMID: 4891956

Nikaido68: Nikaido H (1968). "Biosynthesis of cell wall lipopolysaccharide in gram-negative enteric bacteria." Adv Enzymol Relat Areas Mol Biol 31;77-124. PMID: 4880218

Ning00: Ning B, Elbein AD (2000). "Cloning, expression and characterization of the pig liver GDP-mannose pyrophosphorylase. Evidence that GDP-mannose and GDP-Glc pyrophosphorylases are different proteins." Eur J Biochem 267(23);6866-74. PMID: 11082198

Szumilo93: Szumilo T, Drake RR, York JL, Elbein AD (1993). "GDP-mannose pyrophosphorylase. Purification to homogeneity, properties, and utilization to prepare photoaffinity analogs." J Biol Chem 268(24);17943-50. PMID: 7688733

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Accorsi89: Accorsi A, Piatti E, Piacentini MP, Gini S, Fazi A (1989). "Isoenzymes of phosphoglucomutase from human red blood cells: isolation and kinetic properties." Prep Biochem 19(3);251-71. PMID: 2533352

Alajmo90: Alajmo E, de Meester W, Polli G (1990). "Facial nerve involvement: macroscopic and clinical evidence, therapeutic approach." Acta Otorhinolaryngol Ital 10 Suppl 29;35-42. PMID: 2177945

Albig88: Albig W, Entian KD (1988). "Structure of yeast glucokinase, a strongly diverged specific aldo-hexose-phosphorylating isoenzyme." Gene 73(1);141-52. PMID: 3072253

Aleshin98: Aleshin AE, Zeng C, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB (1998). "The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate." Structure 6(1);39-50. PMID: 9493266

Asensio58: Asensio C, Sols A (1958). "Utilization and phosphorylation of sugars by Escherichia coli." Rev Esp Fisiol 14(4);269-75. PMID: 13658662

Asensio63: Asensio C, Avigad G, Horecker BL (1963). "Preferential galactose utilization in a mutant strain of E. coli." Arch Biochem Biophys 103;299-309. PMID: 14103281

Boles94: Boles E, Liebetrau W, Hofmann M, Zimmermann FK (1994). "A family of hexosephosphate mutases in Saccharomyces cerevisiae." Eur J Biochem 220(1);83-96. PMID: 8119301

Britton68: Britton HG, Clarke JB (1968). "The mechanism of the phosphoglucomutase reaction. Studies on rabbit muscle phosphoglucomutase with flux techniques." Biochem J 110(2);161-80. PMID: 5726186

Cao02: Cao H, Shorey S, Robinson J, Metzger DL, Stewart L, Cummings E, Hegele RA (2002). "GCK and HNF1A mutations in Canadian families with maturity onset diabetes of the young (MODY)." Hum Mutat 20(6);478-9. PMID: 12442280

Colosimo96: Colosimo A, Calabrese G, Gennarelli M, Ruzzo AM, Sangiuolo F, Magnani M, Palka G, Novelli G, Dallapiccola B (1996). "Assignment of the hexokinase type 3 gene (HK3) to human chromosome band 5q35.3 by somatic cell hybrids and in situ hybridization." Cytogenet Cell Genet 74(3);187-8. PMID: 8941369

Csutora05: Csutora P, Strassz A, Boldizsar F, Nemeth P, Sipos K, Aiello DP, Bedwell DM, Miseta A (2005). "Inhibition of phosphoglucomutase activity by lithium alters cellular calcium homeostasis and signaling in Saccharomyces cerevisiae." Am J Physiol Cell Physiol 289(1);C58-67. PMID: 15703203

Curtis75: Curtis SJ, Epstein W (1975). "Phosphorylation of D-glucose in Escherichia coli mutants defective in glucosephosphotransferase, mannosephosphotransferase, and glucokinase." J Bacteriol 122(3);1189-99. PMID: 1097393

Dai99: Dai N, Schaffer A, Petreikov M, Shahak Y, Giller Y, Ratner K, Levine A, Granot D (1999). "Overexpression of Arabidopsis hexokinase in tomato plants inhibits growth, reduces photosynthesis, and induces rapid senescence." Plant Cell 11(7);1253-66. PMID: 10402427

Duckworth73: Duckworth HW, Barber BH, Sanwal BD (1973). "The interaction of phosphoglucomutase with nucleotide inhibitors." J Biol Chem 248(4);1431-5. PMID: 4568817

Fazi90: Fazi A, Piacentini MP, Piatti E, Accorsi A (1990). "Purification and partial characterization of the phosphoglucomutase isozymes from human placenta." Prep Biochem 20(3-4);219-40. PMID: 2149596

Fu95: Fu L, Bounelis P, Dey N, Browne BL, Marchase RB, Bedwell DM (1995). "The posttranslational modification of phosphoglucomutase is regulated by galactose induction and glucose repression in Saccharomyces cerevisiae." J Bacteriol 177(11);3087-94. PMID: 7768805

Furuta96: Furuta H, Nishi S, Le Beau MM, Fernald AA, Yano H, Bell GI (1996). "Sequence of human hexokinase III cDNA and assignment of the human hexokinase III gene (HK3) to chromosome band 5q35.2 by fluorescence in situ hybridization." Genomics 36(1);206-9. PMID: 8812439

Giese05: Giese JO, Herbers K, Hoffmann M, Klosgen RB, Sonnewald U (2005). "Isolation and functional characterization of a novel plastidic hexokinase from Nicotiana tabacum." FEBS Lett 579(3);827-31. PMID: 15670855

Glaser98: Glaser B, Kesavan P, Heyman M, Davis E, Cuesta A, Buchs A, Stanley CA, Thornton PS, Permutt MA, Matschinsky FM, Herold KC (1998). "Familial hyperinsulinism caused by an activating glucokinase mutation." N Engl J Med 338(4);226-30. PMID: 9435328

Hansen03: Hansen T, Schonheit P (2003). "ATP-dependent glucokinase from the hyperthermophilic bacterium Thermotoga maritima represents an extremely thermophilic ROK glucokinase with high substrate specificity." FEMS Microbiol Lett 226(2);405-11. PMID: 14553940

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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