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:


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 Image

Reaction and Disease Links

EC # (IUBMB): 2.7.1.1 2.7.1.1 2.7.1.1 2.7.1.1
Brenda: 2.7.1.1
OMIM: 125851 125853 138079 602485 606176 606391
KEGG: 2645
Rhea: 22740 16125 17825 11028
Reactome : R-HSA-170822 R-HSA-210745 R-HSA-5619073 R-HSA-5619107 R-HSA-70171 R-HSA-9615017

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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