Glucokinase

GLUCOKINASE
  • Glucokinase (GK) or hexokinase IV is one of the four hexokinases that phosphorylate glucose to Glucose-6-phosphate by an irreversible enzymatic reaction .
  • It is the first step of both glycogen synthesis and glycolysis.
DIFFERENCE BETWEEN GLUCOKINASE AND OTHER HEXOKINASE
  • Glucokinase acts in Liver and beta cells of pancreas whereas the nonspecific HK-I is found in all tissues including liver, brain,nerve tissue and erythrocytes.Liver contains both GK (HK-IV) and HK-I, but GK is the predominant isoenzyme.
  • Glucose is not inhibited by Glucose-6 -phosphate whereas other Hexokinase are inhibited by Glucose-6 -phosphate by feeedback inhibition.
  • Glucokinase is induced by insulin, high Km and Vmax.
  1. GK has a low affinity for glucose.
  2. The rate of the phosphorylation reaction catalyzed by GK is therefore controlled by the glucose concentration.
  3. The activity of GK is increased by glucose feeding and by insulin and is decreased during fasting and in insulin lack (i.e., diabetes). In this regard, GK is an inducible enzyme whose activity is increased by glucose or by insulin.
  4. The nonspecific HK-I has a high affinity for glucose.
  5. HK-I catalyzes phosphorylation in all tissues, therefore, it is not controlled by glucose concentration.
ACTION OF GLUCOKINASE IN LIVER AND PANCREAS

Liver
  • Glucokinase enzyme plays an important role in regulating blood glucose levels after feeding.
  • Because GK activity rises rapidly as the glucose concentration rises, it serves as a central metabolic switch to shift hepatic carbohydrate metabolism between fed and fasting states. Phosphorylation of glucose to glucose-6-phosphate by GK facilitates storage of glucose as glycogen and disposal by glycolysis.
Pancreas:
  • Beta cells release insulin in response to rising levels of glucose.
  • Glucokinase in beta cells serves as a glucose sensor, amplifying insulin secretion as blood glucose rises.
DISEASES CAUSED BY MUTATIONS IN GLUCOKINASE
  • GK mutations as manifested in maturity onset of diabetes of the young Type II (MODY II) in humans , and persistent hyperinsulinemic hypoglycemia of infancy (PHHI) 
Exam Question
  • Glucokinase enzyme plays an important role in regulating blood glucose levels after feeding.
  • Glucokinase is not inhibited by Glucose-6-phosphate.
  • Insulin increases the activity of Glucokinase.
  • The rate-limiting enzyme in Glycolysis is Glucokinase.
  • Insulin acts on Glucokinase enzyme in glycoysis.

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