Lecture 4 — Gluconeogenesis

Gluconeogenesis (overview): Synthesis of glucose (primarily from non-carbohydrate sources) to maintain blood glucose during fasting. Primary site (liver & kidneys): Mainly occurs in liver and kidneys, with contributions from other tissues such as GI epithelium. Fasting function: Ensures continued glucose availability when dietary carbohydrate is limited. Glucogenic substrates (overview): Uses glucogenic amino acids, lactate, pyruvate, and glycerol as carbon sources. Pathway direction opposite glycolysis (concept): Reverses glycolysis’s overall output, but uses distinct bypass strategies to overcome irreversible glycolytic steps. Bypasses (conceptual barriers): Uses alternative reactions to get around “locked” glycolytic control points. Key bypass enzyme themes: Major irreversible bypass steps include regulation concepts around conversion steps such as pyruvate carboxylation and PEP formation. Fructose-1,6-bisphosphatase control concept: A key regulatory step influenced by cellular signaling through fructose-2,6-bisphosphate. F-2,6-BP regulation logic: Fructose-2,6-bisphosphate acts as a control signal that shifts gluconeogenesis vs glycolysis tendency. **Hormonal regulation (glucagon/ins