You are treating a 12-year-old male patient exhibiting severe episodes of hypoglycemia. Measurement of circulating insulin and glucagon levels indicate that they are normal and responsive to cycles of feeding and fasting. The hypoglycemia can most easily be explained as a defect in which of the following processes?

Question

Quizplus · Accepted Answer

Hepatic gluconeogenesis is crucial for maintaining blood glucose levels during fasting. A defect in this process can lead to hypoglycemia despite normal insulin and glucagon levels. The hepatic form of hexokinase (glucokinase), in this patient, most likely harbors a mutation that results in a significantly reduced K_m relative to normal glucokinase. Hepatic glucokinase normally has a K_m significantly higher than that of the hexokinase that is expressed in other insulin-responsive tissues such as adipose tissue and skeletal muscle. This prevents the liver from trapping glucose, thereby ensuring that peripheral tissues such as the brain and muscle have easy access to dietary carbohydrate. In the case of this patient, the expression of a variant glucokinase with a K_m similar to that of muscle hexokinase would result in significant trapping of glucose inside hepatocytes. The outcome would be expected to be periods of hypoglycemia as observed in this patient.

You Are Treating a 12-Year-Old Male Patient Exhibiting Severe Episodes