Glucokinase
(hexokinase IV or D) is a cytoplasmic enzyme that phosphorylates glucose
and triggers glucose utilization and metabolism. Glucokinase
occurs in cells in the liver, pancreas, gut, and brain of humans and
most other vertebrates. In
each of these organs it plays an important role in the regulation of
carbohydrate metabolism by acting as a glucose sensor, triggering shifts
in metabolism or cell function in response to rising or falling levels
of glucose, such as occur after a meal or when fasting.
Glucokinase expressed in liver and pancreas is thought to be a component of the glucose sensor controlling plasma glucose levels. Glucose-mediated activation of the enzyme in pancreatic β cells ultimately stimulates insulin secretion, while that in liver enhances hepatic glucose uptake and glycogen synthesis. The critical role of glucokinase in glucose homeostasis is indicated by enzyme variants observed in human subjects. Glucokinase variants with decreased activity are associated with maturity-onset diabetes of the young type 2 (MODY-2).
Fig 1. shows ribbon drawing of the glucokinase structure complexed with glucose (red, ball-and-stick model) and compound A (yellow, ball-and-stick model). The spatial relationship of the large domain (blue) and the small domain (cyan) exhibited a closed form. The two domains are connected by connecting regions I–III (green). The 13 helix (magenta) is included in the small domain of the closed form. (Kenji Kamata et al. Structural Basis for Allosteric Regulation of the Monomeric Allosteric Enzyme Human Glucokinase. Structure 2012)
Fig 1.
| Structure of
bacterial glucokinase |
Page 1 |
| Binding of
glucokinase to other proteins |
Page 2 |
| GSK-GKRP changes upon binding | Page 3 |
| GSK-GKRP interactions | Page 4 |
| Mutations in
GKRP |
Page 5 |