Question

A patient presents in your surgery with an inability to maintain blood sugar levels in long periods (~20 hours) between meals. Tests show that glucose is converted to lactate normally in liver in the well-fed state, and that pyruvate carboxylase and phosphoenolpyruvate carboxykinase have normal activities in liver in periods between meals. Your colleague reminds you that glucagon stimulates glycogen degradation, so you administer glucagon to the patient (who was well fed prior to the test) and find that blood sugar rises in response as normal. What pathway is defective in this patient, and what enzyme do you suspect has a reduced activity? Explain your reasoning.

Answer 1

The answer will be fructose 1,6-bisphosphatase.

Explanation: As long periods of fasting (~20 hours) occurs, here gluconeogenesis is more important process. Glucagon helps to produce glucose-1-phosphate from glycogen which ultimately converted to glucose with the help glucose-6-phosphatase enzyme. As after giving glucagon blood sugar level rises, so glucose-6-phosphatase enzyme must be normal. Also glucose to lactate conversion is normal & pyruvate carboxylase & phosphoenolpyruvate carboxykinase are normal. So, defective enzyme most probably lie between steps of glucose-6-phosphate & fructose 1,6-bisphosphate. As glycolysis is normal, so glucose 6-phosphate can be converted to fructose 6-phosphate. That leaves fructose 1,6-bisphosphatase which is particular for gluconeogenesis most probably defective.