Gluconeogenesis is a metabolic process that synthesizes glucose from non-carbohydrate compounds.
Gluconeogenesis is the synthesis of new glucose molecules from pyruvate, lactate, glycerol, or the amino acids alanine or glutamine. This process takes place primarily in the liver during periods of low glucose, that is, under conditions of fasting, starvation, and low carbohydrate diets. Gluconeogenesis is considered as the reverse process of glycolysis, but with different enzymes.
The three key enzymes are pyruvate carboxylase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase. Pyruvate carboxylase converts pyruvate into oxaloacetate, which is then converted into phosphoenolpyruvate by phosphoenolpyruvate carboxykinase. These two enzymes replace pyruvate kinase in glycolysis.
Fructose-1,6-bisphosphatase converts fructose-1,6-bisphosphate to fructose-6-phosphate which replaces phosphofructokinase-1 in glycolysis. This is the rate-limiting step in gluconeogenesis. Fructose-1,6-bisphosphatase is activated by ATP directly and glucagon indirectly by decreased levels of fructose 2,6-bisphosphate. It is inhibited by AMP directly and insulin indirectly by increased levels of fructose-2,6-bisphosphate.
Glucose-6-phosphatase converts glucose-6-phosphate to glucose, which replaces glucokinase in glycolysis. This enzyme is found in the endoplasmic reticulum of the liver.
A lot of the enzymes in gluconeogenesis and glycolysis, while might not be the same or are shared, are governed by le chateliers principle due to the reversibility of the reactions.
Practice Questions
Khan Academy
Hypoglycemia and carbohydrate metabolism
MCAT Official Prep (AAMC)
Section Bank B/B Section Question 72
Section Bank B/B Section Passage 11 Question 81
Practice Exam 1 B/B Section Passage 9 Question 51
Key Points
• Gluconeogenesis occurs in the liver and sometimes in the kidney
• Gluconeogenesis has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase
• The rate-limiting enzyme is fructose-1,6-bisphosphatase
• Pyruvate carboxylase is inhibited by ADP and stimulated by Acetyl-CoA
• Phosphoenolpyruvate carboxykinase is inhibited by insulin and stimulated by glucagon and cortisol
• Fructose 1,6-bisphosphatase is inhibited by fructose-2,6-bisphosphate and AMP and stimulated by citrate, ATP, and fructose-1,6-bisphosphate
• Glucose 6-phosphatase is inhibited by insulin and glucose-6-phosphate
Key Terms
Gluconeogenesis: the synthesis of glucose from non-carbohydrate precursors
Pyruvate carboxylase: catalyzes the irreversible carboxylation of pyruvate to form oxaloacetate
Fructose bisphosphatase: an enzyme that converts fructose-1,6-bisphosphate to fructose 6-phosphate in gluconeogenesis
Glucose 6-phosphatase: an enzyme that hydrolyzes glucose 6-phosphate, resulting in the creation of a phosphate group and free glucose
Adenosine triphosphate (ATP): a multifunctional nucleoside triphosphate used in cells as a coenzyme, often called the “molecular unit of energy currency” in intracellular energy transfer
Le Chatelier’s principle: changes in the temperature, pressure, volume, or concentration of a system will result in predictable and opposing changes in the system in order to achieve a new equilibrium state.
