Defective GFPT1 does not transfer an amino group from L-Gln to F6P to form GlcN6P

Stable Identifier
R-HSA-4085027
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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Defective GFPT1 does not transfer an amino group from L-Gln to F6P to form GlcN6P
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Glucosamine-fructose 6-phosphate aminotransferases 1 and 2 (GFPT1,2) are the first and rate-limiting enzymes in the hexosamine synthesis pathway, and thus formation of hexosamines like N-acetylglucosamine (GlcNAc). These enzymes probably play a role in limiting the availability of substrates for the N- and O-linked glycosylation of proteins. GFPT1 and 2 are required for normal functioning of neuromuscular synaptic transmission. Defects in GFPT1 cause myasthenia, congenital, with tubular aggregates 1 (CMSTA1; MIM:610542), characterised by altered muscle fibre morphology and impaired neuromuscular junction development (Senderek et al. 2011). The missense mutations observed do not always result in significant reduction in enzyme activity, but biopsies show reduced amounts of GFPT1 protein suggesting increased turnover or defective translation (Senderek et al. 2011). Example mutations are R111C, W240*, D348Y, T15A and T147Qfs*61 (Senderek et al. 2011).
Literature References
PubMed ID Title Journal Year
21310273 Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect

Senderek, J, Müller, JS, Dusl, M, Strom, TM, Guergueltcheva, V, Diepolder, I, Laval, SH, Maxwell, S, Cossins, J, Krause, S, Muelas, N, Vilchez, JJ, Colomer, J, Mallebrera, CJ, Nascimento, A, Nafissi, S, Kariminejad, A, Nilipour, Y, Bozorgmehr, B, Najmabadi, H, Rodolico, C, Sieb, JP, Steinlein, OK, Schlotter, B, Schoser, B, Kirschner, J, Herrmann, R, Voit, T, Oldfors, A, Lindbergh, C, Urtizberea, A, von der Hagen, M, Hübner, A, Palace, J, Bushby, K, Straub, V, Beeson, D, Abicht, A, Lochmüller, H

Am J Hum Genet 2011
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Catalyst Activity

glutamine-fructose-6-phosphate transaminase (isomerizing) activity of GFPT1 mutants [cytosol]

Physical Entity
GFPT1 mutants [cytosol] (Homo sapiens)
Activity
glutamine-fructose-6-phosphate transaminase (isomerizing) activity (GO:0004360)
Normal reaction
GFPT1,2 transfer an amino group from L-Gln to F6P to form GlcN6P (Homo sapiens)
Functional status

Loss of function of GFPT1 mutants [cytosol]

Normal Entity
Disease Entity
Status
Disease
Cross References
Mondo
Authored
Jassal, B  (2013-08-01)
Reviewed
Spillmann, D  (2015-04-30)
Created
Jassal, B  (2013-08-01)
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