Gene Details: GCK
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General Information
Gene Name: GCK (Hexokinase-4)
Synonym:
Short Names: HK4;
Alternative Names: Glucokinase;Hexokinase type IV;Hexokinase-D;
Notes:
- HK4 catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to corresponding hexose 6-phosphate.
- Mainly expressed in pancreas and liver, it exhibits weak affinity for D-glucose compared to other hexokinases.
Description from Dr.Glyco-GPT:
Write a 100-350 word essay about the enzyme human GCK. Provide information related to enzyme: i) function, ii) reaction pathways, ii) Location, and iv) diseases. In writing include these four subheadings ### Function Human GCK, or glucokinase, is an enzyme that plays a critical role in glucose metabolism. GCK catalyzes the phosphorylation of glucose to glucose-6-phosphate, the first and rate-limiting step in glycolysis. Unlike other hexokinases, GCK has a higher Km for glucose, meaning it is active only when glucose levels are elevated, such as after a meal. This allows GCK to act as a glucose sensor, particularly in the liver and pancreatic beta cells, regulating insulin secretion and maintaining blood glucose homeostasis. ### Reaction Pathways GCK is a key enzyme in the glycolysis pathway. It facilitates the conversion of glucose to glucose-6-phosphate, which can then enter several metabolic pathways, including glycolysis for energy production, the pentose phosphate pathway for generating NADPH and ribose, or glycogenesis for storing glucose as glycogen. In the liver, GCK helps regulate the balance between glucose storage and glucose utilization, while in the pancreas, it helps modulate insulin release in response to blood glucose levels. ### Location GCK is primarily located in the liver and pancreatic beta cells, where it plays distinct roles in glucose metabolism. In the liver, GCK helps regulate the storage of glucose as glycogen and its release into the bloodstream. In pancreatic beta cells, GCK serves as a glucose sensor, linking glucose levels to insulin secretion. GCK’s tissue-specific roles make it a central enzyme in maintaining overall glucose homeostasis in the body. ### Diseases Mutations in the GCK gene are associated with several forms of diabetes, most notably maturity-onset diabetes of the young type 2 (MODY2). MODY2 is characterized by mild, non-progressive hyperglycemia due to reduced glucokinase activity, which impairs glucose sensing and insulin secretion. Additionally, GCK mutations can lead to congenital hyperinsulinism, where excessive insulin is produced due to unregulated glucokinase activity, causing hypoglycemia. The critical role of GCK in glucose metabolism makes it a key target for understanding and managing various metabolic disorders related to blood glucose regulation.
Catalytic Activity

Reaction and Disease Links
Brenda:
2.7.1.1
KEGG: 2645
Transcript levels (Cell lines and Single cell data) URL
CRISPR-knockout

CRISPR-activation

CRISPR-inactivation

Top 10 TFs
TF | Score |
---|---|
ZNF580 | 0.009890 |
RBFOX2 | 0.009122 |
SMARCC2 | 0.008978 |
HSF1 | 0.008295 |
TRIM28 | 0.008213 |
RERE | 0.008094 |
DMAP1 | 0.007952 |
SMAD2 | 0.007948 |
SSRP1 | 0.007908 |
RING1 | 0.007890 |
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