Why does fructose 6 phosphate inhibit glucokinase?

[whatdidigetinto]

i found this explanation on wikipedia:
''Fructose 6-phosphate binds to the same site of GKRP, but enhances the ability of GKRP to bind and inactivate GK.'''
The thing is, even though this explains it, why doesn't glucose 6 phosphate inhibit glucokinase? Why does it have to be fructose 6 phosphate? i'm finding it hard to memorize conceptually.

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[Myxedema]

i found this explanation on wikipedia:
''Fructose 6-phosphate binds to the same site of GKRP, but enhances the ability of GKRP to bind and inactivate GK.'''
The thing is, even though this explains it, why doesn't glucose 6 phosphate inhibit glucokinase? Why does it have to be fructose 6 phosphate? i'm finding it hard to memorize conceptually.

Remember that this occurs in the liver. In the fasting stage, glycogen is pen-ultimately broken down to glucose-6-phosphate. If glucose-6-phosphate were to activate glucokinase, the glucose that would be released by glucose-6-phosphatase would become glucose-6-phosphate again. That would result in a vicious cycle. Instead, by activation of fructose-6-phosphate, this is avoided.

 

[whatdidigetinto]

Thank you so much. It makes so much more sense now.

 

[whatdidigetinto]

Remember that this occurs in the liver. In the fasting stage, glycogen is pen-ultimately broken down to glucose-6-phosphate. If glucose-6-phosphate were to activate glucokinase, the glucose that would be released by glucose-6-phosphatase would become glucose-6-phosphate again. That would result in a vicious cycle. Instead, by activation of fructose-6-phosphate, this is avoided.

Actually you didnt answer my question. My question was why doesnt glucose 6 phosphate INHIBIT GLUCOKINASE instead of fructose 6 phosphate. You answered a totally different question.

 

[Myxedema]

Actually you didnt answer my question. My question was why doesnt glucose 6 phosphate INHIBIT GLUCOKINASE instead of fructose 6 phosphate. You answered a totally different question.

As far as I know, glucose-6-phosphate doesn't regulate glucokinase, F6P and glucose does, through GKRP: F6P inactivates glucokinase by facilitating its binding to GKRP (and translocation to nucleus). Conversely, in the presence of glucose, glucokinase is released from GKRP, enters cytosol and phosphorylates glucose.

As to why it's important that F6P regulates it instead of G6P, I've explained it in the previous post.

Summary: Substrate glucose activates enzyme, indirect product F6P inhibits it.

 

[firstaid2012]

isnt it that glucokinase has a high vmax, GLUcokinase is a Glutton it cant be satisfied. it has no direct inhibitions. i dont know im kinda confused now.

 

[Myxedema]

isnt it that glucokinase has a high vmax, GLUcokinase is a Glutton it cant be satisfied. it has no direct inhibitions. i dont know im kinda confused now.

Glucokinase, as one of the rate-limiting steps of glycolysis, is tightly controlled:

- Glucose and F6P, activates and inactives glucokinase respectively, via GKRP
- LCFAs allosterically inhibit glucokinase. (This one one of the reasons why insulin resistance and hyperglycemia is seen in obesty)
- Low-energy state (low ATP, high AMP) and high blood glucose levels cause transcriptional upregulation of glucokinase

 

[firstaid2012]

thank you

 

[aspiringmd1015]

why does fructose 6 po4 inhibit glucokinase?

 

[facting20170101]

In the liver, in the fasting stage, Glycogenolysis and Gluconeogenesis are main pathways. That glucose will be used by RBCs and the brain. The liver should stop synthesizing glycogens with that glucose. So Fructose-6-P inhibits the glucokinase
glucokinase and GLUT2 exist in the liver and b cells in the island.