Defective MPI does not isomerize Fru6P to Man6P

Stable Identifier
R-HSA-3781832
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
9585601 Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein syndrome with hepatic-intestinal presentation

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

Am. J. Hum. Genet. 1998
9525984 Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy

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

J. Clin. Invest. 1998
12756558 Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapies

Marquardt, T, Denecke, J

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

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

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

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

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)

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

Hum Mutat 2000
Participants
Participates
Catalyst Activity

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

Normal reaction
Functional status

Loss of function of MPI mutants [cytosol]

Status
Authored
Reviewed
Created
Cite Us!