Defective GCK does not phosphorylate Glc to form G6P

Stable Identifier
Reaction [transition]
Homo sapiens
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Cytosolic glucokinase (GCK) (as well as three isoforms of hexokinase) catalyse the irreversible reaction of alpha-D-glucose (Glc) and ATP to form alpha-D-glucose-6-phosphate (G6P) and ADP, the first step in glycolysis. In the body, GCK is found only in hepatocytes and pancreatic beta cells. GCK has a high Km for Glc therefore is active when Glc is abundant such as the fed state. The rate of glucose metabolism in liver and pancreas is a function of GCK activity.

Defects in GCK are can cause maturity-onset diabetes of the young 2 (MODY2; MIM:125851), a heritable early onset form of type II diabetes. Mutations in GCK decrease the responsiveness of the beta cell to glucose leading to elevated glucose levels in the blood. GCK was the first MODY gene to be indentified and its mutations are the largest subset causing MODY, currently more than 600 across UK, Spanish and French populations. GCK utations causing MODY2 include E279*, T228M, G261R, A378T, E339K and G229R (Froguel et al. 1992, Vionnet et al. 1992, Stoffel et al. 1992, Vits et al. 2006, Shen et al. 2011).
Literature References
PubMed ID Title Journal Year
1570017 Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus

Takeda, J, Zouali, H, Lesage, S, Stoffel, M, Bell, GI, Yasuda, K, Velho, G, Iris, F, Vionnet, N, Passa, P

Nature 1992
21104275 Insight into the biochemical characteristics of a novel glucokinase gene mutation

Wang, H, Shen, Y, Weng, J, Liang, H, Cai, M

Hum. Genet. 2011
1545870 Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus

Butel, MO, Zouali, H, Sun, F, Lesage, S, Froguel, P, Clément, K, Velho, G, Vaxillaire, M, Fougerousse, F, Vionnet, N

Nature 1992
16965331 Identification of novel and recurrent glucokinase mutations in Belgian and Luxembourg maturity onset diabetes of the young patients

Mathieu, C, Van den Bruel, A, De Schepper, J, Beauloye, V, Massa, G, Giri, M, Nobels, F, Storm, K, de Beaufort, C, Dahan, K, Vits, L, Beckers, D, Wuyts, W, Imschoot, SV, Rooman, R, Nollet, A, Bourguignon, JP, Craen, M, Vanhaverbeke, G, Vanfleteren, E

Clin. Genet. 2006
1502186 Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus

Lesage, S, Harrison, RW, Vionnet, N, Takeda, J, Weber, IT, Pilkis, SJ, Zouali, H, Stoffel, M, Nishi, S, Froguel, P

Proc Natl Acad Sci U S A 1992
Catalyst Activity

glucokinase activity of GCK mutants [cytosol]

Normal reaction
Functional status

Loss of function of GCK mutants [cytosol]

Name Identifier Synonyms
maturity-onset diabetes of the young DOID:0050524 MODY, MASON-TYPE DIABETES
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