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Old 04-29-2011
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Biochemistry Glucokinase Trapping of Glucose

THE FUNCTION OF GLUCOKINASE IS TO TRAP GLUCOSE IN FORM OF
GLUCOSE 6-PHOSPAHTE

NEAR COMPLETE DEFICIENCY OF GLUCOKINASE ACTIVITY IS ASSOCIATED WITH NEONATAL TYPE-1 DM

MUTATIONS IN GLUCOKINASE GENE THAT DECREASE Km CAUSE

1) HYPERINSULINEMIA

2) HYPOGLYCEMIA

HOW TO EXPLAIN IT??
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Old 04-30-2011
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Decreased Km means increased potency. This leads to Glucokinase binding to glucose more avidly and converting it into Glucose - 6 - phosphate. This traps Glucose within the cells making it unable to stay in blood leading to hypoglycemia.

I suppose hyperinsulinemia is connected to Glucokinase hence to facilitate its avid binding to glucose, insulin is secreted in big amount. Please correct me if i am wrong.
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Quote:
Originally Posted by donofitaly View Post
Decreased Km means increased potency. This leads to Glucokinase binding to glucose more avidly and converting it into Glucose - 6 - phosphate. This traps Glucose within the cells making it unable to stay in blood leading to hypoglycemia.

I suppose hyperinsulinemia is connected to Glucokinase hence to facilitate its avid binding to glucose, insulin is secreted in big amount. Please correct me if i am wrong.

BIG DAEL IS WITH HYPERINSULINEMIA..

I M ALSO NT SURE BOUT THAT...
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Old 04-30-2011
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GLUCOKINASE is like glucose sensor for the pancreatic beta cells.

  1. Inc. activity of this enzyme-----> more glucose utilization in Beta cells more ATP.
  2. More ATP---> closure of the ATP sensitive K channels in the Beta cells leading to depolarization of the beta cells.
  3. Calcium influx----> release of Insulin from Beta cells.
Abscence of Glucokinase leads to failure of release of insulin from Beta cells or DM

Inc. Km means less affinity of the enzyme to its substrate thats glucose manifesting as DM again.

Dec. Km of this enzyme= more affinity & more glucose utilization by the beta cells leading to more release of Insulin causing hyperinsulinemia & hypoglycemia.

Sulphonylureas
block this K channel leading to depolarization of the beta cells & causing relase of insulin from the pancreatic beta cells.

Diazoxide a K channel activator causes hyper polarization by opening the K channel of the beta cells & blocking the release of insulin. Used for treatment of Insulinomas.
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Old 04-30-2011
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Quote:
Originally Posted by ikrimachoudry View Post
THE FUNCTION OF GLUCOKINASE IS TO TRAP GLUCOSE IN FORM OF
GLUCOSE 6-PHOSPAHTE
NEAR COMPLETE DEFICIENCY OF GLUCOKINASE ACTIVITY IS ASSOCIATED WITH NEONATAL TYPE-1 DM
MUTATIONS IN GLUCOKINASE GENE THAT DECREASE Km CAUSE
1)HYPERINSULINEMIA
2)HYPOGLYCEMIA
HOW TO EXPLAIN IT??
Your premises are worded strangely, which makes it seem more confusing than it really is. I will rewrite them a little differently before addressing the question:
  • The function of glucokinase is to trap glucose in beta cells and hepatocytes.
  • Several hundred mutations have been identified which decrease glucokinse activity - heterozygosity for these mutations leads to neonatal insulin-dependent diabetes (a type of MODY). This is characterized by hyperglycemia and hypoinsulinemia.
  • Half a dozen mutations have been identified that produce a hyperinsulinemic, hypoglycemic condition: these include gain-of-function mutations and mutations decreasing the Km.
At its normal Km, glucokinase (expressed in beta cells and hepatocytes) has low activity at low glucose concentrations (i.e. normal fasting blood glucose), leaving the glucose for hexokinase, which is present in all cells. As blood glucose concentration rises, normal glucokinase activity increases. A mutated glucokinase with a lower Km is active at lower blood glucose concentrations, even at normal fasting blood glucose, effectively lowering the trigger level for insulin release to below fasting blood glucose (also, remember that, unlike hexokinase, glucokinase is not allosterically inhibited by its product, G6P). This leads to hyper insulinemia and hypoglycemia, since the level of blood glucose maintained even by hepatic gluconeogenesis is enough to keep the beta cells in this poor child pumping out insulin.

Hope that helps!
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