Question

In the liver and the pancreas, hexokinase and glucokinase phosphorylate glucose. Glucokinase is active only when the blood concentration of glucose is high. How might glucokinase differ kinetically from hexokinase so as to function only at high glucose levels?

Short answer

Glucokinase has a higher Km value than hexokinase, meaning it is active only at high glucose concentrations.

Step-by-step solution

Understand the Role of Hexokinase and Glucokinase

Hexokinase and glucokinase are enzymes that facilitate the phosphorylation of glucose to glucose-6-phosphate. While hexokinase is present in most tissues and is always active, glucokinase is mainly found in the liver and pancreas, and it is specifically active at high blood glucose levels.

Analyze the Kinetic Properties of Enzymes

Enzyme kinetics often involve parameters such as Km (Michaelis constant), which indicates the affinity of the enzyme for the substrate. A lower Km value means higher affinity and that the enzyme is active even at low substrate concentrations.

Differentiate Between Hexokinase and Glucokinase in Terms of Km

Hexokinase has a low Km value, meaning it has high affinity for glucose and functions at low glucose concentrations typical of all bodily cells. In contrast, glucokinase has a higher Km value, indicating a lower affinity for glucose, and thus it only becomes significantly active when glucose concentrations are high, like after consuming a meal.

Interpret the Functional Implications of Km Difference

The higher Km of glucokinase allows it to act as a glucose sensor in the liver and pancreas by being only effective during high glucose conditions. This means glucokinase helps in glucose regulation by storing excess glucose as glycogen in the liver.

Key concepts

Hexokinase

Hexokinase is a crucial enzyme found in many tissues throughout the body. Its main role is to phosphorylate glucose, adding a phosphate group to form glucose-6-phosphate. This is an important step because it helps trap glucose inside cells, allowing them to use it for energy. Hexokinase is always active, regardless of the glucose concentration in the blood. This is because it has a very low Michaelis constant (\( K_m \)), which means it has a high affinity for glucose.

• This enzyme works efficiently even when glucose concentrations are quite low.
• It ensures that tissues such as the brain and muscles have a constant supply of energy.
• Because hexokinase is always active, it helps in maintaining basic cellular functions.

Glucokinase

Glucokinase, found mainly in the liver and pancreas, plays a different but equally important role. Unlike hexokinase, glucokinase is designed to activate only when there are high levels of glucose in the blood, such as after a meal. This specificity is because glucokinase has a much higher \( K_m \) value compared to hexokinase.

• It shows lower affinity for glucose, requiring higher substrate concentrations for activation.


• This enzyme functions effectively as a glucose sensor.


• Activated glucokinase uses the excess glucose to store energy in the liver as glycogen.

Glucokinase's activity pattern helps in regulating blood sugar levels and storing excess energy, which can be crucial for metabolic balance.

Michaelis constant (Km)

The Michaelis constant (\( K_m \) ) is a key concept in enzyme kinetics. It helps determine the relationship between enzyme activity and substrate concentration. A lower \( K_m \) value indicates that an enzyme has a high affinity for its substrate, meaning it can achieve significant activity even at low substrate levels. Conversely, a higher \( K_m \) value means lower affinity, requiring higher substrate concentrations for the enzyme to function effectively.

• This concept explains why hexokinase, with its low \( K_m \), is active even when glucose levels are low.


• For glucokinase, a higher \( K_m \) means it becomes active only when blood glucose levels are elevated.


• Understanding \( K_m \) helps in understanding how different enzymes control metabolic pathways and respond to cellular needs.

Overall, \( K_m \) plays a critical role in dictating enzyme efficiency and their role in homeostasis.