Gluconeogenesis Flashcards
(6 cards)
Overview
Essentially a reverse glycolysis except 3 rate limiting steps involving hexokinase, phosphofructokinase and pyruvate kinase are bypassed. Complete pathway only in liver. Mainly cytoplasmic, pyruvate carboxylase mitochondrial. Substrates includes lactate, glycerol and a.a skeleton. If an aa backbone can only be made into acyl-CoA, it cannot be made into glucose. If it can be made into pyruvate or a Kreb’s cycle intermediate, it can be made into glucose.
Pyruvate → Oxaloacetate
Step 1. Pyruvate carboxylase, a mitochondrial enzyme, adds a carbon to pyruvate to form oxaloacetate. This reaction consumes ATP and is activated by acetyl-CoA. Acetyl-CoA builds up when energy is high, signalling the need to store carbon as glucose. This step is the first bypass of glycolysis.
Oxaloacetate → (PEP)
Step 2. PEPCK (phosphoenolpyruvate carboxykinase) removes the added carbon as CO₂ and phosphorylates oxaloacetate using GTP to form phosphoenolpyruvate. PEPCK expression varies by tissue. This is the second ATP-consuming bypass step of glycolysis and prepares the carbon skeleton to move toward glucose.
PEP to Fructose 1,6-bisphosphate
Step 3. PEP progresses through several reversible glycolytic steps that require ATP. It forms intermediates like 3-phosphoglycerate and glyceraldehyde-3-phosphate, eventually producing fructose 1,6-bisphosphate. These steps don’t require new enzymes, but do consume energy.
Fructose 1,6-bisphosphate → Fructose 6-phosphate
Step 4. Fructose 1,6-bisphosphatase removes a phosphate group to convert fructose 1,6-bisphosphate into fructose 6-phosphate. This step is highly regulated: AMP and fructose 2,6-bisphosphate inhibit it, while low AMP levels promote gluconeogenesis by switching off glycolysis.
Fructose 6-phosphate → Glucose 6-phosphate
Step 5. Fructose 6-phosphate is converted to glucose 6-phosphate through reversible glycolytic steps. No bypass enzyme is needed at this stage.
