Question

Inborn errors of metabolism are disorders resulting from genetic defects of metabolic genes that regulate energy metabolism. Although rare, there are 2 reported inborn errors of metabolism affecting the process of gluconeogenesis. The first results in a deficiency of fructose-1,6-bisphosphate (FBPase) and the second results in a deficiency in phosphoenolpyruvate carboxylase (PEPCK). Both deficiencies present with the symptom of hypoglycermia (low blood glucose) early in life during periods of fasting. a) What are three main sources of glucose normally used to maintain euglycemia (normal blood glucose) in healthy individuals? b) Explain how deficiencies in either FBPase or PEPCK can lead to this symptom specifically during fasting. BE SURE TO REFERENCE THE SOURCES THAT YOU LISTED IN PART A. c) The hypoglycemia associated with PEPCK is often less frequent and less profound than in FBPase deficiency. Please explain this (hint think about the precursors for gluconeogenesis and how they are utilized within the gluconeogenenic pathway).

Answer 1

a) the three main sources of glucose are carbohydrates, fats and proteins.

b) PEP carboxylase is present in plants , the correct name of the enzyme is PEP carboxykinase

FBPASe and PEP carboxykinase are both involved in gluconeogenesis which is why their deficiency causes hypoglycemia specially during fasting. DUring fasting the body do not have any of the three sources mentioned above from which it can extract glucose so it has to use its internal sources and synthesise glucose through gluconeogenesis.

c) This is because PEPCK provide for the substrate for gluconeogenesis as it catalysis the breakdown of oxaloacetate into PEP and carbon dioxide. however, other sources like amino acids etc can be broken down to provide carbon skeleton. However, the step that is catalyzed by FBPase is not and cannot be replaced or bypassed by any other source or enzyme which is why hypoglycemia due to FBPase is more aggressive than PEPCK