Question

Are all of these statements true? (number 4 seems iffy)

1. All glucose consumed is absorbed by the small intestine, which then travels via the hepatic portal vein to the liver. Normal liver glucokinase have a relatively high Km value of 10mM, which means it has a lower affinity for glucose. These kinetics allow for the liver to function as a blood glucose buffering system, as glucokinase will only convert glucose to glycogen stores when blood glucose levels (BGL) are higher than appropriate. This means that when BGL are low, glucose is able to leave the liver and is available to other cells to meet their energy demands.

2. Since glucokinase controls the rate at which glucose enters the glycolytic pathway, a mutation in glucokinase that lowers its Km value and increases its affinity for glucose is problematic and will lead to hypoglycemia 20 minutes after a meal as well as after 8 hours of fasting.

3. After a meal when BGL are high, the mutated glucokinase’s higher affinity for glucose, will cause inappropriate uptake and conversion of glucose to glucose-6-phosphate (G6P). Unlike the hexokinase isoforms found in other cell types, glucokinase is not inhibited by its product G6P and will continue to capture and store G6P, regardless of the body’s demand for glucose. The consequence of malfunction in the livers buffering system is hypoglycemia.

4. After an 8 hour fast, mutated glucokinase may continue to synthesize unnecessary glycogen. However, upon the secretion of glucagon, the activity of glucokinase may be inhibited and the pathway of gluconeogenesis may be stimulated. In this case, the liver will attempt to produce glucose via gluconeogenesis but will be unsuccessful. This is because the mutated glucokinase has a greater tendency to phosphorylate glucose, so any glucose produced will be immediately converted to G6P and trapped in the liver, regardless of hypoglycemic conditions.

Answer 1

Mutated glucokinase may continue to synthesize unnecessary glycogen. However, upon the secretion of glucagon, the activity of glucokinase may be inhibited and the pathway of gluconeogenesis may be stimulated. In this case, the liver will attempt to produce glucose via gluconeogenesis but will be unsuccessful. This is because the mutated glucokinase has a greater tendency to phosphorylate glucose, so any glucose produced will be immediately converted to Glucose6Phosphate and trapped in the liver.