Glucokinase And Hexokinase Kinetic Properties

578 Chapter 15 Principles of Metabolic Regulation: Glucose and Glycogen la el Re la el Re

Hexokinase Kinetic Properties

10 15 20

Glucose concentration (mM)

FIGURE 15-16 Comparison of the kinetic properties of hexokinase IV (glucokinase) and hexokinase I. Note the sigmoidicity for hexokinase IV and the much lower Km for hexokinase I. When blood glucose rises above 5 mM, hexokinase IV activity increases, but hexokinase I is already operating near Vmax at 5 mM glucose and cannot respond to an increase in glucose concentration. Hexokinase I, II, and

III have similar kinetic properties.

10 15 20

Glucose concentration (mM)

FIGURE 15-16 Comparison of the kinetic properties of hexokinase IV (glucokinase) and hexokinase I. Note the sigmoidicity for hexokinase IV and the much lower Km for hexokinase I. When blood glucose rises above 5 mM, hexokinase IV activity increases, but hexokinase I is already operating near Vmax at 5 mM glucose and cannot respond to an increase in glucose concentration. Hexokinase I, II, and

III have similar kinetic properties.

predominant hexokinase isozyme of liver is hexokinase

IV (glucokinase), which differs in three important respects from hexokinases I—III of muscle. First, the glucose concentration at which hexokinase IV is half-saturated (about 10 mM) is higher than the usual concentration of glucose in the blood. Because an efficient glucose transporter in hepatocytes (GLUT2; see Fig. 11-31) rapidly equilibrates the glucose concentrations in cytosol and blood, the high Km of hexokinase IV allows its direct regulation by the level of blood glucose (Fig. 15-16). When the blood glucose concentration is high, as it is after a meal rich in carbohydrates, excess glucose is transported into hepatocytes, where hexokinase IV

converts it to glucose 6-phosphate. Because hexokinase IV is not saturated at 10 mm glucose, its activity continues to increase as the glucose concentration rises to 10 mm or more.

Second, hexokinase IV is subject to inhibition by the reversible binding of a regulatory protein specific to liver (Fig. 15-17). The binding is much tighter in the presence of the allosteric effector fructose 6-phosphate. Glucose competes with fructose 6-phosphate for binding and causes dissociation of the regulatory protein from hexokinase IV, relieving the inhibition. Immediately after a carbohydrate-rich meal, when blood glucose is high, glucose enters the hepatocyte via GLUT2 and activates hexokinase IV by this mechanism. During a fast, when blood glucose drops below 5 mm, fructose 6-phosphate triggers the inhibition of hexokinase IV by the regulatory protein, so the liver does not compete with other organs for the scarce glucose. The mechanism of inhibition by the regulatory protein is interesting: the protein anchors hexokinase IV inside the nucleus, where it is segregated from the other enzymes of glycolysis in the cytosol (Fig. 15-17). When the glucose concentration in the cell rises, it equilibrates with glucose in the nucleus by transport through the nuclear pores. Glucose causes dissociation of the regulatory protein, and hexokinase IV enters the cytosol and begins to phosphorylate glucose.

Third, hexokinase IV is not inhibited by glucose 6-phosphate, and it can therefore continue to operate when the accumulation of glucose 6-phosphate completely inhibits hexokinases I-III.

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Essentials of Human Physiology

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Responses

  • adriana
    Who does hexokinase affect. blood glucose?
    5 years ago
  • HAROLD HAYES
    Is half saturated at much lower concentrations (0.1mM) than is its isozyme?
    5 years ago
  • ruta
    Is hexokinase or glucokinase half saturated at much lower concentrations .1mM than is its isozyeme>?
    4 years ago
  • anthony
    What amino acids affect glucokinase?
    2 years ago

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