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:||Biosynthesis → Carbohydrates Biosynthesis → Sugars Biosynthesis → Sugar Nucleotides Biosynthesis → GDP-sugar Biosynthesis|
Some taxa known to possess this pathway include : Arabidopsis thaliana col, Candida albicans, Escherichia coli K-12 substr. MG1655, Homo sapiens, Pseudomonas aeruginosa, Pyrococcus horikoshii, Saccharomyces cerevisiae, Spinacia oleracea, Sus scrofa
Mannose-containing glycoconjugates, such as protein N- and C-glycans, some O-glycans, glycosylphosphatidylinositol (GPI) protein membrane anchors, and some glycolipids, have a variety of important functions. These functions include the promotion of correct folding, solubility, stability and intracellular sorting of proteins, promoting the enzymatic, hormonal or receptor activity of many proteins, and the formation of cell surface glycocalyces, extracellular matrices and protective cell walls. In addition, glycoproteins are known to play major roles in cell-cell interactions (see protein N-glycosylation (eukaryotic, high mannose)) [Garami01].
GDP-α-D-mannose is the critical metabolite of the mannose activation pathway for glycoconjugate synthesis in eukaryotes, as it is utilized directly or indirectly as a mannose donor for all mannosylation reactions.
In addition, GDP-α-D-mannose is a precursor for the biosynthesis of several important compounds, including GDP-L-fucose (see GDP-L-fucose biosynthesis I (from GDP-D-mannose)) L-ascorbate (see L-ascorbate biosynthesis I (L-galactose pathway)), 2-O-α-mannosyl-D-glycerate (see mannosylglycerate biosynthesis I) and GDP-α-D-rhamnose (see GDP-D-rhamnose biosynthesis).
The crucial role of GDP-α-D-mannose is supported by the finding that deletion of certain genes in this pathway are lethal in Saccharomyces cerevisiae and Candida albicans [Hashimoto97, Warit00, Kepes88, Orlean88].
Unification Links: EcoCyc:PWY-5659
Garami01: Garami A, Ilg T (2001). "Disruption of mannose activation in Leishmania mexicana: GDP-mannose pyrophosphorylase is required for virulence, but not for viability." EMBO J 20(14);3657-66. PMID: 11447107
Hashimoto97: Hashimoto H, Sakakibara A, Yamasaki M, Yoda K (1997). "Saccharomyces cerevisiae VIG9 encodes GDP-mannose pyrophosphorylase, which is essential for protein glycosylation." J Biol Chem 272(26);16308-14. PMID: 9195935
Orlean88: Orlean P, Albright C, Robbins PW (1988). "Cloning and sequencing of the yeast gene for dolichol phosphate mannose synthase, an essential protein." J Biol Chem 263(33);17499-507. PMID: 3053713
Warit00: Warit S, Zhang N, Short A, Walmsley RM, Oliver SG, Stateva LI (2000). "Glycosylation deficiency phenotypes resulting from depletion of GDP-mannose pyrophosphorylase in two yeast species." Mol Microbiol 36(5);1156-66. PMID: 10844699
Ahn11: Ahn J, Chung BK, Lee DY, Park M, Karimi IA, Jung JK, Lee H (2011). "NADPH-dependent pgi-gene knockout Escherichia coli metabolism producing shikimate on different carbon sources." FEMS Microbiol Lett 324(1);10-6. PMID: 22092758
Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554
Aoyama94a: Aoyama K, Haase AM, Reeves PR (1994). "Evidence for effect of random genetic drift on G+C content after lateral transfer of fucose pathway genes to Escherichia coli K-12." Mol Biol Evol 1994;11(6);829-38. PMID: 7815923
Baveja86: Baveja UK, Jyoti AS, Kaur M, Agarwal DS, Anand BS, Nanda R (1986). "Isoenzyme studies of Giardia lamblia isolated from symptomatic cases." Aust J Exp Biol Med Sci 64 ( Pt 2);119-26. PMID: 2943257
Bertrand76: Bertrand O, Kahn A, Cottreau D, Boivin P (1976). "Human leukocyte glucose-phosphate-isomerase purification by affinity elution and immunological study." Biochimie 58(3);261-7. PMID: 819039
Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043
Byrne14: Byrne RT, Chen SH, Wood EA, Cabot EL, Cox MM (2014). "Escherichia coli genes and pathways involved in surviving extreme exposure to ionizing radiation." J Bacteriol 196(20);3534-45. PMID: 25049088
Canonaco01: Canonaco F, Hess TA, Heri S, Wang T, Szyperski T, Sauer U (2001). "Metabolic flux response to phosphoglucose isomerase knock-out in Escherichia coli and impact of overexpression of the soluble transhydrogenase UdhA." FEMS Microbiol Lett 204(2);247-52. PMID: 11731130
Chang04: Chang DE, Smalley DJ, Tucker DL, Leatham MP, Norris WE, Stevenson SJ, Anderson AB, Grissom JE, Laux DC, Cohen PS, Conway T (2004). "Carbon nutrition of Escherichia coli in the mouse intestine." Proc Natl Acad Sci U S A 101(19);7427-32. PMID: 15123798
Charusanti10: Charusanti P, Conrad TM, Knight EM, Venkataraman K, Fong NL, Xie B, Gao Y, Palsson BO (2010). "Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene." PLoS Genet 6(11);e1001186. PMID: 21079674
Chemler10: Chemler JA, Fowler ZL, McHugh KP, Koffas MA (2010). "Improving NADPH availability for natural product biosynthesis in Escherichia coli by metabolic engineering." Metab Eng 12(2);96-104. PMID: 19628048
Conklin99: Conklin PL, Norris SR, Wheeler GL, Williams EH, Smirnoff N, Last RL (1999). "Genetic evidence for the role of GDP-mannose in plant ascorbic acid (vitamin C) biosynthesis." Proc Natl Acad Sci U S A 96(7);4198-203. PMID: 10097187
Cordeiro03: Cordeiro AT, Godoi PH, Silva CH, Garratt RC, Oliva G, Thiemann OH (2003). "Crystal structure of human phosphoglucose isomerase and analysis of the initial catalytic steps." Biochim Biophys Acta 1645(2);117-22. PMID: 12573240
Desvergnes12: Desvergnes S, Courtiol-Legourd S, Daher R, Dabrowski M, Salmon L, Therisod M (2012). "Synthesis and evaluation of malonate-based inhibitors of phosphosugar-metabolizing enzymes: class II fructose-1,6-bis-phosphate aldolases, type I phosphomannose isomerase, and phosphoglucose isomerase." Bioorg Med Chem 20(4);1511-20. PMID: 22269276
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