Defective MPI does not isomerize Fru6P to Man6P

Stable Identifier
Reaction [transition]
Homo sapiens
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Mannose 6-phosphate isomerase (MPI) normally isomerises fructose 6-phosphate (Fru6P) to mannose 6-phosphate (Man6P) in the cytosol. Man6P is a precursor in the synthesis of GDP-mannose and dolichol-phosphate-mannose, required for mannosyl transfer reactions in the N-glycosylation of proteins. Defects in MPI cause congenital disorder of glycosylation 1b (MPI-CDG, previously known as CDG1b,; MIM:602579), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Schollen et al. 2000). Unlike PMM2-CDG (CDG1a), there is no neurological involvement with MPI-CDG. Instead, patients present predominantly with diarrhoea, failure to thrive and protein-losing enteropathy (Pelletier et al. 1986). MPI-CDG is one of two CDGs that can be treated with oral mannose supplementation, but can be fatal if left untreated (Marquardt & Denecke 2003). MPI mutations causing MPI-CDG are R219Q, S102L, M138T, R295H and A38Gfs*26 (Niehues et al. 1998, Schollen et al. 2000, Jaeken et al. 1998, Vuillaumier-Barrot et al. 2002).
Literature References
PubMed ID Title Journal Year
9525984 Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy

Schiebe-Sukumar, M, Zimmer, KP, Körner, C, Niehues, R, Hasilik, M, von Figura, K, Wu, R, Koch, HG, Harms, E, Reiter, K, Harms, HK, Freeze, HH, Marquardt, T, Alton, G

J. Clin. Invest. 1998
9585601 Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein syndrome with hepatic-intestinal presentation

Henri, H, Dionisi-Vici, C, Schollen, E, Van Schaftingen, E, Saudubray, JM, Matthijs, G, Bertini, E, de Lonlay, P, Jaeken, J, Carchon, H

Am. J. Hum. Genet. 1998
12756558 Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapies

Denecke, J, Marquardt, T

Eur. J. Pediatr. 2003
3080572 Secretory diarrhea with protein-losing enteropathy, enterocolitis cystica superficialis, intestinal lymphangiectasia, and congenital hepatic fibrosis: a new syndrome

Brochu, P, Pelletier, VA, Morin, CL, Galéano, N, Roy, CC, Weber, AM

J. Pediatr. 1986
12414827 Protein losing enteropathy-hepatic fibrosis syndrome in Saguenay-Lac St-Jean, Quebec is a congenital disorder of glycosylation type Ib

Seta, N, Durand, G, Vuillaumier-Barrot, S, Barnier, A, Saudubray, JM, Le Bizec, C, Prevost, C, Pelletier, V, de Lonlay, P, Mitchell, G

J. Med. Genet. 2002
10980531 Genomic organization of the human phosphomannose isomerase (MPI) gene and mutation analysis in patients with congenital disorders of glycosylation type Ib (CDG-Ib)

Freeze, H, Huijmans, JG, Schollen, E, Patterson, M, Pronicka, E, Babovic-Vuksanovic, D, Van Diggelen, OP, Matthijs, G, Adamowicz, M, Dorland, L, Marquardt, T, Winchester, B, Imtiaz, F, de Koning, TJ

Hum Mutat 2000
Catalyst Activity

mannose-6-phosphate isomerase activity of MPI mutants [cytosol]

Normal reaction
Functional status

Loss of function of MPI mutants [cytosol]

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