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Gluconeogenesis

Gluconeogenesis. The de novo synthesis of glucose and its role in preventing hypoglycemia. Gluconeogenesis: Overview Figure 13-2. General Features. Tissues: liver (80%) kidneys (20%) Subcellular location of enzymes pyruvate carboxylase: mitochondrial glucose-6-phosphatase: ER

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Gluconeogenesis

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  1. Gluconeogenesis The de novo synthesis of glucose and its role in preventing hypoglycemia

  2. Gluconeogenesis: OverviewFigure 13-2

  3. General Features • Tissues: • liver (80%) • kidneys (20%) • Subcellular location of enzymes • pyruvate carboxylase: mitochondrial • glucose-6-phosphatase: ER • all other enzymes cytoplasmic

  4. Malate Shuttle • OAA produced in mitochondria • mitochondrial membrane impermeable to OAA • malate transporter in mito. Membrane • malate dehydrogenase in both mito and cyto • NADH produced in cyto also used in gluconeogenesis.

  5. Energetics of Gluconeogenesisfigure 13-1 • Pyruvate Carboxylase • 2 ATPs • PEP Carboxykinase • 2 GTPs • 3-P-glycerate kinase • 2 ATPs • Glyceraldehyde-3-P dehydrogenase • 2NADH

  6. Precursers for gluconeogenesisfigure 13-2 • Glycerol • derived from adipocyte lipolysis • hepatic glycerol kinase

  7. Precursers for gluconeogenesisFigure13-3 • Lactate • RBC • muscle • the Cori Cycle

  8. Precursers for gluconeogenesisfigure 13-4 • Alanine and other amino acids • transamination of pyruvate • pyruvate derived from glycolysis or from amino acid degradation • alanine cycle

  9. Coordinated Regulation of Gluconeogenesis and Glycolysis • Gluconeogenesis and Glycolysis are regulated by similar effector molecues but in the opposite direction • avoid futile cycles • PK vs PC&PEPCK • PFK-1 vs FDP’tase • GK vs G6P’tase

  10. Coordinated Regulation of Gluconeogenesis and Glycolysis • Regulation of enzyme quantity • Fasting: glucagon, cortisol • induces gluconeogenic enzymes • represses glycolytic enzymes • liver making glucose • Feeding: insulin • induces glycolytic enzymes • represses gluconeogenic enzymes • liver using glucose

  11. Coordinated Regulation of Gluconeogenesis and Glycolysis • Short-term Hormonal Effects • Glucagon, Insulin • cAMP & F2,6P2 • PFK-2 & FBPase-2 • A Bifunctional enzyme • cAMP • Inactivates PFK-2 • Activates FBPase-2 • Decreases F2,6P2 • Reduces activation of PFK-1 • Reduces inhibition of FBPase-1 • Low blood sugar results in • Hi gluconeogenesis • Lo glycolysis

  12. Coordinated Regulation of Gluconeogenesis and Glycolysis • Allosteric Effects • Pyruvate kinase vs Pyruvate carboxylase • PK - Inhibited by ATP and alanine • PC - Activated by acetyl CoA • Fasting results in gluconeogenesis • PFK-1 vs FBPase-1 • FBPase-1 inhibited by AMP & F2,6P2 • PFK-1 activated by AMP and & F2,6P2 • Feeding results in glycolysis

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