HK1,2,3,GCK phosphorylate Glc to form G6P

Stable Identifier
R-HSA-70420
Type
Reaction
Species
Homo sapiens
Compartment
Synonyms
alpha-D-Glucose + ATP => alpha-D-glucose 6-phosphate + ADP
Locations in the PathwayBrowser
Summation

Cytosolic glucokinase and the three isoforms of hexokinase catalyze the irreversible reaction of glucose and ATP to form glucose 6 phosphate and ADP. In the body glucokinase is found only in hepatocytes and pancreatic beta cells. Glucokinase and the hexokinase enzymes differ in that glucokinase has a higher Km than the hexokinases and is less readily inhibited by the reaction product. As a result, glucokinase should be inactive in the fasting state when glucose concentrations are low but in the fed state should have an activity proportional to glucose concentration. These features are thought to enable efficient glucose uptake and retention in the liver, and to function as a sensor of glucose concentration coupled to insulin release in pancreatic beta cells (Thorens 2001). Glucokinase mutations are associated with MODY2, a heritable early onset form of type II diabetes (Tanizawa et al. 1991; Takeda et al. 1993). Three human hexokinase enzymes have been characterized, HK1 (Aleshin et al. 1998), HK2 (Lehto et al. 1995), and HK3 (Rijksen at al. 1982).

Literature References
PubMed ID Title Journal Year
1871135 Human liver glucokinase gene: cloning and sequence determination of two alternatively spliced cDNAs

Tanizawa, Y, Koranyi, LI, Welling, CM, Permutt, MA

Proc Natl Acad Sci U S A 1991
8786021 Human hexokinase II gene: exon-intron organization, mutation screening in NIDDM, and its relationship to muscle hexokinase activity

Lehto, M, Huang, X, Davis, EM, Le Beau, MM, Laurila, E, Eriksson, KF, Bell, GI, Groop, LC

Diabetologia 1995
8325892 Structure/function studies of human beta-cell glucokinase. Enzymatic properties of a sequence polymorphism, mutations associated with diabetes, and other site-directed mutants.

Takeda, J, Gidh-Jain, M, Xu, LZ, Froguel, P, Velho, G, Vaxillaire, M, Cohen, D, Shimada, F, Makino, H, Nishi, S, Stoffel, M, Vionnet, N, St. Charles, R, Harrison, RW, Weber, IT, Bell, GI, Pilkis, SJ

J Biol Chem 1993
9493266 The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate

Aleshin, AE, Zeng, C, Bourenkov, GP, Bartunik, HD, Fromm, HJ, Honzatko, RB

Structure 1998
7150652 Compartmentation of hexokinase in human blood cells. Characterization of soluble and particulate enzymes.

Rijksen, G, Staal, GE, Beks, PJ, Streefkerk, M, Akkerman, JW

Biochim Biophys Acta 1982
11780755 GLUT2 in pancreatic and extra-pancreatic gluco-detection (review)

Thorens, B

Mol Membr Biol 2001
Participants
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
glucokinase activity of glucokinase and hexokinases [cytosol]
Physical Entity
Activity
Orthologous Events
Cross References
Rhea