Hexokinase vs Glucokinase

[chromuffin]

I have two questions pertaining to these enzymes.

Is the Km of Glucokinase relatively high as an internal measure to ensure that glycogenesis occurs with relatively high levels of glucose?

Why does HK have a low Vmax? Is this somehow related to the fact that glycolysis occurs when energy stores are high? Not really understanding this.

Edit: I guess my real second question should be more along the lines of: how does a low Km conceptually equate to a low Vmax? I understand that Km is the concentration at 0.5Vmax and that Km inversely explains affinity.

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[intubesteak]

Glucokinase has a lower Km than Hexokinase so that muscles are able to get the first grab at glucose in the blood. You don't need the liver picking up glucose (and then storing it) unless there is plenty to go around. Muscles get first dibs. There could be other reasons I'm sure, but this is what I was taught.

Edit: To be sure were on the same page, the main purpose of glucokinase/hexokinase is to sequester glucose inside the cell so it can't diffuse back across the membrane.

For your second question, I would say that Km does not necessarily equate to a low Vmax for a given enzyme. You can have a large Km and a small Vmax, or a large Km and a high Vmax. It would depend on the particular enzyme. If you are talking about changing variables for a given reaction, thats a whole other topic. I'm not sure if that helps, but I'm also not sure exactly what you are asking to be honest... but I took a stab at it.

 

[chromuffin]

Glucokinase has a lower Km than Hexokinase so that muscles are able to get the first grab at glucose in the blood. You don't need the liver picking up glucose (and then storing it) unless there is plenty to go around. Muscles get first dibs. There could be other reasons I'm sure, but this is what I was taught.

Edit: To be sure were on the same page, the main purpose of glucokinase/hexokinase is to sequester glucose inside the cell so it can't diffuse back across the membrane.

For your second question, I would say that Km does not necessarily equate to a low Vmax for a given enzyme. You can have a large Km and a small Vmax, or a large Km and a high Vmax. It would depend on the particular enzyme. If you are talking about changing variables for a given reaction, thats a whole other topic. I'm not sure if that helps, but I'm also not sure exactly what you are asking to be honest... but I took a stab at it.

Thanks for your reply! I think your explanation for the first question really solidified my knowledge. I hadn't thought of them as glucose sequestering enzymes but it makes perfect sense. As for the second question, I'm mostly trying to understand the table on page 86 of FA 2016 where it talks about hexokinase having a lower Vmax than Glucokinase.

 

[intubesteak]

Thanks for your reply! I think your explanation for the first question really solidified my knowledge. I hadn't thought of them as glucose sequestering enzymes but it makes perfect sense. As for the second question, I'm mostly trying to understand the table on page 86 of FA 2016 where it talks about hexokinase having a lower Vmax than Glucokinase.

Yeah I don't know what the underlying reason for that would be. But I don't think it has to do with Km. Yes, Km and Vmax are related by the MM equation... but that is comparing Km to Vmax for a particular enzyme. The relationship between Km and Vmax between two different enzymes is apples to oranges. Does that help at all?

 

[Taco Time]

Km is higher in cells with GLUT-2 transporters (found in liver and pancreatic B cells) = think of these cells as responsible for monitoring the blood glucose levels and maintaining proper functioning = also know that these cells use glucokinase to convert glucose into G6P --> form ATP --> use ATP to block K+ channels --> K+ builds up in cells (depolarization) --> activates the Ca++ channels --> Ca++ comes in and induces release of insulin --> glucose then taken up out of serum

Km is lower in skeletal muscle (and most other cells), which has GLUT-4, this allows muscle cells to grab up the glucose much more avidly, initially. These other cells of the body instead utilize hexokinase for the same step that glucokinase is used for, breaking down glucose.

The point is that the regulatory cells using GLUT-2 and glucokinase are more responsive to a big flux of glucose and can thus put out more insulin if needed like when Grandpa Sal has a bowl of ice cream. But, if Grandpa Sal sticks with a saltine cracker, there's no need to release a ton of insulin to induce hypoglycemia and a seizure or something--higher Km value means that these cells aren't hyper-responsive at small amounts of glucose while the high Vmax means that if there is a need to put out a ton of insulin, the body is able to do so. Hence, why glucokinase has a higher Vmax and a higher Km (associated with GLUT-2 and very precise insulin release) while hexokinase isn't involved in the fine-tuning details as much since it is found in cells like striated muscle cells.

This system allows for fine tuning to provide an adequate response to sudden changes in increased glucose states and works really well. More glucose comes into the body --> regulatory cells can attenuate a precise response and release of insulin --> eventually glucose is taken up out of serum and a normal level returns to the serum --> less insulin release

 

[chromuffin]

Km is higher in cells with GLUT-2 transporters (found in liver and pancreatic B cells) = think of these cells as responsible for monitoring the blood glucose levels and maintaining proper functioning = also know that these cells use glucokinase to convert glucose into G6P --> form ATP --> use ATP to block K+ channels --> K+ builds up in cells (depolarization) --> activates the Ca++ channels --> Ca++ comes in and induces release of insulin --> glucose then taken up out of serum

Km is lower in skeletal muscle (and most other cells), which has GLUT-4, this allows muscle cells to grab up the glucose much more avidly, initially. These other cells of the body instead utilize hexokinase for the same step that glucokinase is used for, breaking down glucose.

The point is that the regulatory cells using GLUT-2 and glucokinase are more responsive to a big flux of glucose and can thus put out more insulin if needed like when Grandpa Sal has a bowl of ice cream. But, if Grandpa Sal sticks with a saltine cracker, there's no need to release a ton of insulin to induce hypoglycemia and a seizure or something--higher Km value means that these cells aren't hyper-responsive at small amounts of glucose while the high Vmax means that if there is a need to put out a ton of insulin, the body is able to do so. Hence, why glucokinase has a higher Vmax and a higher Km (associated with GLUT-2 and very precise insulin release) while hexokinase isn't involved in the fine-tuning details as much since it is found in cells like striated muscle cells.

This system allows for fine tuning to provide an adequate response to sudden changes in increased glucose states and works really well. More glucose comes into the body --> regulatory cells can attenuate a precise response and release of insulin --> eventually glucose is taken up out of serum and a normal level returns to the serum --> less insulin release

Thank you for this detailed description. Makes perfect sense!

 

[Mit Patel]

Glucokinase has a lower Km than Hexokinase so that muscles are able to get the first grab at glucose in the blood. You don't need the liver picking up glucose (and then storing it) unless there is plenty to go around. Muscles get first dibs. There could be other reasons I'm sure, but this is what I was taught.

Edit: To be sure were on the same page, the main purpose of glucokinase/hexokinase is to sequester glucose inside the cell so it can't diffuse back across the membrane.

For your second question, I would say that Km does not necessarily equate to a low Vmax for a given enzyme. You can have a large Km and a small Vmax, or a large Km and a high Vmax. It would depend on the particular enzyme. If you are talking about changing variables for a given reaction, thats a whole other topic. I'm not sure if that helps, but I'm also not sure exactly what you are asking to be honest... but I took a stab at it.

Just a quick correction... glucokinase has a HIGHER Km than hexokinase because it has a lower affinity for glucose in comparison to Hexokinase.

 

[Phloston]

I have two questions pertaining to these enzymes.

Is the Km of Glucokinase relatively high as an internal measure to ensure that glycogenesis occurs with relatively high levels of glucose?

Why does HK have a low Vmax? Is this somehow related to the fact that glycolysis occurs when energy stores are high? Not really understanding this.

Edit: I guess my real second question should be more along the lines of: how does a low Km conceptually equate to a low Vmax? I understand that Km is the concentration at 0.5Vmax and that Km inversely explains affinity.

More important that peripheral tissue (muscle [and adipocytes]) pick up glucose before the liver, so affinity is higher peripherally and Km lower for HK.

The liver's job is to buffer the blood glucose level when it gets too high, so its saturation capacity is higher (higher Vmax). Insulin naturally upregulates GK at the liver in the fed state.

There's a lot to talk about here, but it seems quite a few posters have already given ample response.